Effect of antihypertensive treatment on focal cerebral infarction.

PubMed

Fujii, K; Weno, B L; Baumbach, G L; Heistad, D D

1992-06-01

The goal of the current study was to determine whether treatment of hypertension reduces cerebral infarction after occlusion of the middle cerebral artery in stroke-prone spontaneously hypertensive rats (SHRSPs). Three-month-old SHRSPs received untreated drinking water or drinking water containing cilazapril, an angiotensin converting enzyme inhibitor, or hydralazine and hydrochlorothiazide. After 3 months of treatment, the left middle cerebral artery was occluded and neurological deficit was evaluated. Infarct volume was measured 3 days after occlusion using computer imaging techniques from brain slices. Cilazapril and hydralazine with hydrochlorothiazide were equally effective in reducing systolic blood pressure in SHRSPs. One day after occlusion of the middle cerebral artery, neurological deficit was decreased by both cilazapril and hydralazine with hydrochlorothiazide compared with untreated SHRSPs, and the deficit 3 days after occlusion was decreased significantly only by cilazapril. Infarct volume was 178 +/- 7 mm3 (mean +/- SEM) in untreated SHRSPs, and it was significantly reduced to 117 +/- 15 mm3 by hydralazine with hydrochlorothiazide and to 101 +/- 17 mm3 by cilazapril. Infarct volume in Wistar-Kyoto rats was 27 +/- 16 mm3. Thus, reduction in arterial pressure by hydralazine with hydrochlorothiazide or an angiotensin converting enzyme inhibitor is protective against focal cerebral ischemia in SHRSPs.

Cardiac magnetic resonance imaging parameters as surrogate endpoints in clinical trials of acute myocardial infarction

PubMed Central

2011-01-01

Cardiac magnetic resonance (CMR) offers a variety of parameters potentially suited as surrogate endpoints in clinical trials of acute myocardial infarction such as infarct size, myocardial salvage, microvascular obstruction or left ventricular volumes and ejection fraction. The present article reviews each of these parameters with regard to the pathophysiological basis, practical aspects, validity, reliability and its relative value (strengths and limitations) as compared to competitive modalities. Randomized controlled trials of acute myocardial infarction which have used CMR parameters as a primary endpoint are presented. PMID:21917147

Neuroprotective effect of combined ultrasound and microbubbles in a rat model of middle cerebral artery infarction

NASA Astrophysics Data System (ADS)

Fatar, M.; Griebe, M.; Stroick, M.; Kern, R.; Hennerici, M.; Meairs, S.

2005-03-01

Ultrasound-mediated microbubble thrombolysis (UMT) was performed in a middle cerebral artery occlusion model in rats to evaluate possible effects upon brain infarct volume, apoptosis, IL-6 and TNF-alpha levels, and disruption of the blood-brain barrier (BBB). The results show that infarct volume was significantly reduced (p<0.04) in the microbubble + ultrasound (MB + US) group as compared to control animals. The levels of IL-6 and TNF-alpha concentrations, as markers of tissue damage, were not significantly different. In trypan blue treated animals, no additional BBB disruption was observed for the UMT group. Likewise, there was no increase in apoptotic cell death outside the infarction area in animals treated with MB + US. The results demonstrate that UMT does not have a harmful effect upon ischemic stroke in a middle cerebral artery occlusion model of the rat. The significant reduction in brain infarction following insonation with ultrasound and microbubbles suggests a novel neuroprotective effect in ischemic stroke.

Impact of Leukoaraiosis Burden on Hemispheric Lateralization of the National Institutes of Health Stroke Scale Deficit in Acute Ischemic Stroke.

PubMed

Helenius, Johanna; Goddeau, Richard P; Moonis, Majaz; Henninger, Nils

2016-01-01

The National Institutes of Health Stroke Scale (NIHSS) awards higher deficit scores for infarcts in the dominant hemisphere when compared with otherwise similar infarcts in the nondominant hemisphere. This has been shown to adversely affect stroke recognition, therapeutic decisions, and outcome. However, factors modifying the association between infarct side and deficit severity are incompletely understood. Thus, we sought to determine whether age and age-related leukoaraiosis alter the relation between NIHSS deficit score and the side and volume of infarction. We studied 238 patients with supratentorial, nonlacunar ischemic infarcts prospectively included in our stroke registry between January 2013 and January 2014. NIHSS deficit severity was assessed at the time of presentation. Infarct volumes were assessed by manual planimetry on diffusion-weighted imaging. Leukoaraiosis burden was graded on fluid-attenuated inversion recovery images according to the Fazekas scale and dichotomized to none-to-mild (0-2) versus severe (3-6). Multivariable linear regression with backward elimination was used to identify independent predictors of the admission NIHSS. Left-hemispheric infarction (P<0.001), severe leukoaraiosis (P=0.001), their interaction term (P=0.005), infarct volume (P<0.001), and sex (P=0.013) were independently associated with the NIHSS deficit. Analysis of the individual NIHSS components showed that severe leukoaraiosis was associated with an increase of the lateralizing components of the NIHSS in patients with right-hemispheric infarction (P<0.05). Severe leukoaraiosis substantially attenuates the classic hemispheric lateralization of the NIHSS deficit by relating to greater NIHSS scores of components that are typically assigned to left hemisphere function. © 2015 American Heart Association, Inc.

Distal hyperintense vessels alleviate insula infarction in proximal middle cerebral artery occlusion.

PubMed

Song, Jiacheng; Ma, Zhanlong; Meng, Huan; Yu, Jing; Li, Yan; Hong, Xunning; Shi, Haibin

2016-11-01

Insula involvement in acute cerebral ischemia more likely causes penumbral loss and poor clinical outcome than infarct-sparing insula. Our objective was to prove the hypothesis that abundant collateral circulation represented by distal hyperintense vessels (HV) on MRI alleviates insula infarction and facilitates prognosis. One hundred and fourteen stroke cases with M1 totally occlusion on MR angiography were documented consecutively from 2012 to 2014. The degree of HV was graded as absent, subtle or prominent. Clinical data were recorded retrospectively by reviewing the medical records. The infarct volume on diffusion-weighted image, along with National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS), was used to evaluate the clinical severity and prognosis. The degree of HV was more abundant in insula-uninvolved stroke compared with stroke involving insula infarction (p = 0.026). Insula-involved stroke patients were older (p = 0.039) with a higher percentage of atrial fibrillation history (p = 0.042). Univariate analysis revealed that insula infarction, age, infarct volume and NIHSS predicted unfavorable prognosis of stroke, whereas HV had a favorable effect. The protective effect of HV was confirmed by multivariate analysis. HV is a protective barrier between insula infarction and severity of clinical symptoms among stroke patients.

Effect of ischemic cerebral volume changes on behavior.

PubMed

Lyden, P D; Lonzo, L M; Nunez, S Y; Dockstader, T; Mathieu-Costello, O; Zivin, J A

1997-08-01

Ischemia causes long-term effects on brain volume and neurologic function but the relationship between the two is poorly characterized. We studied the relationships between brain volume and three measures of rodent behavior after cerebral ischemia was induced by injecting several thousand microspheres into the internal carotid arteries of rats. Forty eight hours later, each subject was rated using a global neurologic rating scale. Several weeks later, the subjects were tested for open field activity and visual spatial learning. Post-mortem we measured the volume of the cerebral hemispheres and estimated the volume densities of cortex, white matter, hippocampus, basal ganglia, thalamus, ventricle, and visible infarction. Ischemia caused significant impairment, as measured by the global rating scale; the probability of an abnormal rating was correlated with the number of microspheres trapped in the brains. Visual spatial learning was significantly impaired by ischemia, but this deficit was independent of the count of microspheres, whether the subject was abnormal at 48 h, and whether the left or right hemisphere was embolized. Cerebral hemisphere volume was reduced from 430 mm3 to 376 mm3 (P < 0.05). The cortex was reduced from 22 to 19% of cerebrum (P < 0.05) and the white matter compartment was reduced to similar degree. The lesion volume was 6% of cerebrum, comparable to that seen with other ischemia methods. The global outcome rating was significantly related to total cerebral volume, but not to volume changes in any single compartment. On the other hand, visual spatial learning was significantly influenced by volume changes in the cortex and white matter, but not by the topography of the visible infarctions. Open field activity was not altered by infarction. Our data suggests that the total volume of brain tissue lost to infarction may partially determine global neurological rating independently of the topography of the volume loss. Integrative functions such as learning may depend more on the integrity of specific compartments and less on the total volume of intact brain. The volume of visible cystic infarction was not related to long term behavioral outcome. These results should be confirmed using another method of inducing ischemia.

Quantitative estimation of infarct size by simultaneous dual radionuclide single photon emission computed tomography: comparison with peak serum creatine kinase activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawaguchi, K.; Sone, T.; Tsuboi, H.

1991-05-01

To test the hypothesis that simultaneous dual energy single photon emission computed tomography (SPECT) with technetium-99m (99mTc) pyrophosphate and thallium-201 (201TI) can provide an accurate estimate of the size of myocardial infarction and to assess the correlation between infarct size and peak serum creatine kinase activity, 165 patients with acute myocardial infarction underwent SPECT 3.2 +/- 1.3 (SD) days after the onset of acute myocardial infarction. In the present study, the difference in the intensity of 99mTc-pyrophosphate accumulation was assumed to be attributable to difference in the volume of infarcted myocardium, and the infarct volume was corrected by the ratiomore » of the myocardial activity to the osseous activity to quantify the intensity of 99mTc-pyrophosphate accumulation. The correlation of measured infarct volume with peak serum creatine kinase activity was significant (r = 0.60, p less than 0.01). There was also a significant linear correlation between the corrected infarct volume and peak serum creatine kinase activity (r = 0.71, p less than 0.01). Subgroup analysis showed a high correlation between corrected volume and peak creatine kinase activity in patients with anterior infarctions (r = 0.75, p less than 0.01) but a poor correlation in patients with inferior or posterior infarctions (r = 0.50, p less than 0.01). In both the early reperfusion and the no reperfusion groups, a good correlation was found between corrected infarct volume and peak serum creatine kinase activity (r = 0.76 and r = 0.76, respectively; p less than 0.01).« less

The Influence of Acute Hyperglycemia in an Animal Model of Lacunar Stroke That Is Induced by Artificial Particle Embolization

PubMed Central

Tsai, Ming-Jun; Lin, Ming-Wei; Huang, Yaw-Bin; Kuo, Yu-Min; Tsai, Yi-Hung

2016-01-01

Animal and clinical studies have revealed that hyperglycemia during ischemic stroke increases the stroke's severity and the infarct size in clinical and animal studies. However, no conclusive evidence demonstrates that acute hyperglycemia worsens post-stroke outcomes and increases infarct size in lacunar stroke. In this study, we developed a rat model of lacunar stroke that was induced via the injection of artificial embolic particles during full consciousness. We then used this model to compare the acute influence of hyperglycemia in lacunar stroke and diffuse infarction, by evaluating neurologic behavior and the rate, size, and location of the infarction. The time course of the neurologic deficits was clearly recorded from immediately after induction to 24 h post-stroke in both types of stroke. We found that acute hyperglycemia aggravated the neurologic deficit in diffuse infarction at 24 h after stroke, and also aggravated the cerebral infarct. Furthermore, the infarct volumes of the basal ganglion, thalamus, hippocampus, and cerebellum but not the cortex were positively correlated with serum glucose levels. In contrast, acute hyperglycemia reduced the infarct volume and neurologic symptoms in lacunar stroke within 4 min after stroke induction, and this effect persisted for up to 24 h post-stroke. In conclusion, acute hyperglycemia aggravated the neurologic outcomes in diffuse infarction, although it significantly reduced the size of the cerebral infarct and improved the neurologic deficits in lacunar stroke. PMID:27226775

The real estate factor: quantifying the impact of infarct location on stroke severity.

PubMed

Menezes, Nina M; Ay, Hakan; Wang Zhu, Ming; Lopez, Chloe J; Singhal, Aneesh B; Karonen, Jari O; Aronen, Hannu J; Liu, Yawu; Nuutinen, Juho; Koroshetz, Walter J; Sorensen, A Gregory

2007-01-01

The severity of the neurological deficit after ischemic stroke is moderately correlated with infarct volume. In the current study, we sought to quantify the impact of location on neurological deficit severity and to delineate this impact from that of volume. We developed atlases consisting of location-weighted values indicating the relative importance in terms of neurological deficit severity for every voxel of the brain. These atlases were applied to 80 first-ever ischemic stroke patients to produce estimates of clinical deficit severity. Each patient had an MRI and National Institutes of Health Stroke Scale (NIHSS) examination just before or soon after hospital discharge. The correlation between the location-based deficit predictions and measured neurological deficit (NIHSS) scores were compared with the correlation obtained using volume alone to predict the neurological deficit. Volume-based estimates of neurological deficit severity were only moderately correlated with measured NIHSS scores (r=0.62). The combination of volume and location resulted in a significantly better correlation with clinical deficit severity (r=0.79, P=0.032). The atlas methodology is a feasible way of integrating infarct size and location to predict stroke severity. It can estimate stroke severity better than volume alone.

Volume of Subclinical Embolic Infarct Correlates to Long-term Cognitive Changes following Carotid Revascularization

PubMed Central

Zhou, Wei; Baughman, Brittanie D; Soman, Salil; Wintermark, Max; Lazzeroni, Laura C.; Hitchner, Elizabeth; Bhat, Jyoti; Rosen, Allyson

2016-01-01

OBJECTIVE Carotid intervention is safe and effective in stroke prevention in appropriately selected patients. Despite minimal neurologic complications, procedure-related subclinical microemboli are common and their cognitive effects are largely unknown. In this prospective longitudinal study, we sought to determine long-term cognitive effects of embolic infarcts. METHODS 119 patients including 46% symptomatic patients who underwent carotid revascularization were recruited. Neuropsychological testing was administered preoperatively and at 1, 6, and 12 months postoperatively. Rey Auditory Learning Test (RAVLT) was the primary cognitive measure with parallel forms to avoid practice effort. All patients also received 3T brain MRIs with a diffusion-weighted sequence (DWI) preoperatively and within 48 hours postoperatively to identify procedure-related new embolic lesions. Each DWI lesion was manually traced and input into a neuroimaging program to define volume. Embolic infarct volumes were correlated with cognitive measures. Regression models were used to identify relationships between infarct volumes and cognitive measures. RESULTS A total 587 DWI lesions were identified on 3T MRI in 81.7% of CAS and 36.4% of CEA patients with a total volume of 29327mm3. Among them, 54 DWI lesions were found in CEA patients and 533 in the CAS patients. Four patients had transient postoperative neurologic symptoms and one had a stroke. CAS was an independent predictor of embolic infarct (OR: 6.6 [2.1–20.4], p<.01) and infarct volume (P=.004). Diabetes and contralateral carotid severe stenosis/occlusion had a trend of positive association with infarct volume, while systolic blood pressure more or equal to 140mmHg had a negative association (P=.1, .09, and .1, respectively). There was a trend of improved RAVLT scores overall following carotid revascularization. Significantly higher infarct volumes were observed among those with RAVLT decline. Within the CAS cohort, infarct volume was negatively correlated with short and long-term RAVLT changes (P<0.05). CONCLUSIONS Cognitive assessment of procedure-related subclinical microemboli is challenging. Volumes of embolic infarct correlates with long-term cognitive changes, suggesting that micro-embolization should be considered as a surrogate measure for carotid disease management. PMID:28024850

Semi-quantitative analyses of hippocampal heat shock protein-70 expression based on the duration of ischemia and the volume of cerebral infarction in mice.

PubMed

Choi, Jong-Il; Kim, Sang-Dae; Kim, Se-Hoon; Lim, Dong-Jun; Ha, Sung-Kon

2014-06-01

We investigated the expression of hippocampal heat shock protein 70 (HSP-70) infarction volume after different durations of experimental ischemic stroke in mice. Focal cerebral ischemia was induced in mice by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, both hippocampi were extracted for HSP-70 protein analyses. Slices from each hemisphere were stained with 2,3,5-triphenyltetrazolium chloride (2%), and infarction volumes were calculated. HSP-70 levels were evaluated using western blot and enzyme-linked immunosorbent assay (ELISA). HSP-70 subtype (hsp70.1, hspa1a, hspa1b) mRNA levels in the hippocampus were measured using reverse transcription-polymerase chain reaction (RT-PCR). Cerebral infarctions were found ipsilateral to the occlusion in 10 mice exposed to transient ischemia (5 each in the 30-min and 60-min occlusion groups), whereas no focal infarctions were noted in any of the sham mice. The average infarct volumes of the 2 ischemic groups were 22.28±7.31 mm(3) [30-min group±standard deviation (SD)] and 38.06±9.53 mm(3) (60-min group±SD). Western blot analyses and ELISA showed that HSP-70 in hippocampal tissues increased in the infarction groups than in the sham group. However, differences in HSP-70 levels between the 2 infarction groups were statistically insignificant. Moreover, RT-PCR results demonstrated no relationship between the mRNA expression of HSP-70 subtypes and occlusion time or infarction volume. Our results indicated no significant difference in HSP-70 expression between the 30- and 60-min occlusion groups despite the statistical difference in infarction volumes. Furthermore, HSP-70 subtype mRNA expression was independent of both occlusion duration and cerebral infarction volume.

Impact of Infarct Size on Blood Pressure in Young Patients with Acute Stroke.

PubMed

Bonardo, Pablo; Pantiú, Fátima; Ferraro, Martín; Chertcoff, Anibal; Bandeo, Lucrecia; Cejas, Luciana León; Pacha, Sol; Roca, Claudia Uribe; Rugilo, Carlos; Pardal, Manuel Maria Fernández; Reisin, Ricardo

2018-06-01

Hypertension can be found in up to 80% of patients with acute stroke. Many factors have been related to this phenomenon such as age, history of hypertension, and stroke severity. The aim of our study was to determine the relationship between infarct volume and blood pressure, at admission, in young patients with acute ischemic stroke. Patients younger than 55 years old admitted within 24 hours of ischemic stroke were included. Socio-demographic variables, systolic blood pressure, diastolic blood pressure, and infarct volume at admission were assessed. Statistical analysis: mean and SEM for quantitative variables, percentages for qualitative, and Spearman correlations ( p value < 0.05 was considered statistically significant). Twenty-two patients (12 men), mean age: 44.64 ± 1.62 years. The most frequent vascular risk factors were: hypertension, smoking, and overweight (40.9%). Mean systolic and diastolic blood pressure on admission were: 143.27 ± 6.57 mmHg and 85.14 ± 3.62 mmHg, respectively. Infarct volume: 11.55 ± 4.74 ml. Spearman correlations: systolic blood pressure and infarct volume: p = 0.15 r : -0.317; diastolic blood pressure and infarct volume: p = 0.738 r: -0.76. In our series of young patients with acute ischemic stroke, large infarct volume was not associated with high blood pressure at admission.

Shortened Mean Transit Time in CT Perfusion With Singular Value Decomposition Analysis in Acute Cerebral Infarction: Quantitative Evaluation and Comparison With Various CT Perfusion Parameters.

PubMed

Murayama, Kazuhiro; Katada, Kazuhiro; Hayakawa, Motoharu; Toyama, Hiroshi

We aimed to clarify the cause of shortened mean transit time (MTT) in acute ischemic cerebrovascular disease and examined its relationship with reperfusion. Twenty-three patients with acute ischemic cerebrovascular disease underwent whole-brain computed tomography perfusion (CTP). The maximum MTT (MTTmax), minimum MTT (MTTmin), ratio of maximum and minimum MTT (MTTmin/max), and minimum cerebral blood volume (CBV) (CBVmin) were measured by automatic region of interest analysis. Diffusion weighted image was performed to calculate infarction volume. We compared these CTP parameters between reperfusion and nonreperfusion groups and calculated correlation coefficients between the infarction core volume and CTP parameters. Significant differences were observed between reperfusion and nonreperfusion groups (MTTmin/max: P = 0.014; CBVmin ratio: P = 0.038). Regression analysis of CTP and high-intensity volume on diffusion weighted image showed negative correlation (CBVmin ratio: r = -0.41; MTTmin/max: r = -0.30; MTTmin ratio: r = -0.27). A region of shortened MTT indicated obstructed blood flow, which was attributed to the singular value decomposition method error.

Changes in serum interleukin-33 levels in patients with acute cerebral infarction.

PubMed

Liu, Jingyao; Xing, Yingqi; Gao, Ying; Zhou, Chunkui

2014-02-01

Inflammation is widely considered to be involved in the pathogenesis of cerebral ischemic injury. The balance between inflammatory and anti-inflammatory factors significantly affects the prognosis of patients with cerebral infarction. Interleukin-33 (IL-33), a newly identified member of the interkeukin-1 superfamily, has been found to play very important roles in the inflammation of several human diseases including asthma, inflammatory bowel disease, and central nervous system inflammation. To our knowledge its role in the pathology of acute cerebral infarction has not yet been reported. In this study, we demonstrated that serum IL-33 levels were significantly increased in patients with acute cerebral infarction compared to control patients without acute cerebral infarction. Furthermore, serum IL-33 levels increased with the infarction volume. Our study suggests that IL-33 may be involved in the pathogenesis and/or progression of acute cerebral infarction. Copyright © 2013 Elsevier Ltd. All rights reserved.

In vivo amino acid transport of subacute and chronic cerebral infarction evaluated by 12-18F-phenylalanine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shimosegawa, E.; Miura, S.; Murakami, M.

1994-05-01

On the basis of previous validation of kinetic two-compartment model and the determination of normal values of three parameters (k{sub 1}:influx rate constant, k{sub 2}:outflux rate constant, Vd:distribution volume), PET measurements of in vivo amino acid transport from blood to brain using L-(2-18F)-fluorophenylalanine ({sup 18}F-Phe) were undergone in the patients with cerebral infarction. The purposes of this study are to evaluate the alteration of amino acid transport in subacute and chronic stage of cerebral infarction and to compare with cerebral blood flow (CBF) and oxygen metabolism. Dynamic {sup 18}F-Phe PET studies for 50 minutes were performed in 7 patients withmore » cerebral infarction. The input function was obtained by 27 points of arterial sampling. In all patients, measurements of CBF, cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO{sub 2}), and oxygen extraction fraction (OEF) were made on the same day of {sup 18}F-Phe PET measurement. Each patient was studied twice, within 2 weeks of the onset and 3 months later. Weighted integration technique with table look-up method was applied for the reconstruction of parametric images of {sup 18}F-Phe and ROI analysis of k{sub 1}, k{sub 2}, and Vd. In subacute stage, significant reduction of k{sub 2} value in infarct area was observed when compared to that in periinfarct area (p<0.05) and in normal cortices (p<0.001). k{sub 1} value in this stage showed only slightly decrease in infarct area, therefore, Vd value in infarct area increased significantly compared to normal cortices (p<0.001). In chronic stage, both k{sub 1} and k{sub 2} values in infarct area were significantly lower than that in normal cortices (p<0.001), and corresponding Vd value reduced to normal level. Correlativity between kinetic parameters of {sup 18}F-Phe and CBF or oxygen metabolism was not observed both in subacute and chronic stage of infarction.« less

Neuroprotective effects of Lepidium meyenii (Maca).

PubMed

Pino-Figueroa, Alejandro; Nguyen, Diane; Maher, Timothy J

2010-06-01

The neuroprotective activity of the plant Lepidium meyenii (Maca) was studied in two experimental models: in vitro and in vivo. Crayfish neurons were pretreated with vehicle or the pentane extract from Maca, subjected to H(2)O(2), and their viability determined microscopically and chemically. A significant concentration-neuroprotective effect relationship was demonstrated. The pentane extract was then administered intravenously to rats prior to and following middle cerebral artery occlusion. While infarct volumes were decreased for the lower dose, higher doses increased infarct volumes compared to controls. These results suggest a potential application of Maca as a neuroprotectant.

The inhibitor of 20-HETE synthesis, TS-011, improves cerebral microcirculatory autoregulation impaired by middle cerebral artery occlusion in mice.

PubMed

Marumo, Toshiyuki; Eto, Kei; Wake, Hiroaki; Omura, Tomohiro; Nabekura, Junichi

2010-11-01

20-Hydroxyeicosatetraenoic acid is a potent vasoconstrictor that contributes to cerebral ischaemia. An inhibitor of 20-Hydroxyeicosatetraenoic acid synthesis, TS-011, reduces infarct volume and improves neurological deficits in animal stroke models. However, little is known about how TS-011 affects the microvessels in ischaemic brain. Here, we investigated the effect of TS-011 on microvessels after cerebral ischaemia. TS-011 (0.3 mg·kg(-1) ) or a vehicle was infused intravenously for 1 h every 6 h in a mouse model of stroke, induced by transient occlusion of the middle cerebral artery occlusion following photothrombosis. The cerebral blood flow velocity and the vascular perfusion area of the peri-infarct microvessels were measured using in vivo two-photon imaging. The cerebral blood flow velocities in the peri-infarct microvessels decreased at 1 and 7 h after reperfusion, followed by an increase at 24 h after reperfusion in the vehicle-treated mice. We found that TS-011 significantly inhibited both the decrease and the increase in the blood flow velocities in the peri-infarct microvessels seen in the vehicle-treated mice after reperfusion. In addition, TS-011 significantly inhibited the reduction in the microvascular perfusion area after reperfusion, compared with the vehicle-treated group. Moreover, TS-011 significantly reduced the infarct volume by 40% at 72 h after middle cerebral artery occlusion. These findings demonstrated that infusion of TS-011 improved defects in the autoregulation of peri-infarct microcirculation and reduced the infarct volume. Our results could be relevant to the treatment of cerebral ischaemia. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

Factors that Can Help Select the Timing for Decompressive Hemicraniectomy for Malignant MCA Stroke.

PubMed

Kamran, Saadat; Salam, Abdul; Akhtar, Naveed; Alboudi, Ayman; Kamran, Kainat; Singh, Rajvir; Amir, Numan; Inshasi, Jihad; Qidwai, Uwais; Malik, Rayaz A; Shuaib, Ashfaq

2018-03-06

In patients with malignant middle cerebral artery (MMCA) stroke, a vital clinically relevant question is determination of the speed with which infarction evolves to select the time for decompressive hemicraniectomy [DHC]. A retrospective, multicenter cross-sectional study of patients referred for DHC, based on the criteria of randomized controlled trials, was undertaken to identify factors for selecting the timing of DHC in MMCA stroke, stratified by time [< 48, 48-72, > 72 h]. Infarction volume and infarct growth rate [IGR] were measured on all CT scans. One hundred eighty-two patients [135 underwent DHC and 47 survived without DHC] were included in the analysis. After multivariate adjustment, factors showing the strongest independent association with DHC were patients < 55 years of age, septum pellucidum deviation, temporal lobe involvement, MCA with additional infarcts, and IGR on second CT. Of the five factors identified, different combinations of determining factors were observed in each subgroup. Both first and second IGRs were highest in the < 48, 48-< 72, and > 72 h [p < 0.001]. Patients who survived without surgery had the slowest IGRs. There was no association between time to DHC and infarct volume, although infarct volume was lower in patients who survived without DHC compared to the DHC subgroups. We identify the major risk factors associated with DHC in time-stratified subgroups of patients with MMCA. Evaluation of IGRs between the first and second scan and when possible second and third scan can help in selecting the timing of hemicraniectomy.

Infarct Volume Prediction by Early Magnetic Resonance Imaging in a Murine Stroke Model Depends on Ischemia Duration and Time of Imaging.

PubMed

Leithner, Christoph; Füchtemeier, Martina; Jorks, Devi; Mueller, Susanne; Dirnagl, Ulrich; Royl, Georg

2015-11-01

Despite standardization of experimental stroke models, final infarct sizes after middle cerebral artery occlusion (MCAO) vary considerably. This introduces uncertainties in the evaluation of drug effects on stroke. Magnetic resonance imaging may detect variability of surgically induced ischemia before treatment and thus improve treatment effect evaluation. MCAO of 45 and 90 minutes induced brain infarcts in 83 mice. During, and 3 and 6 hours after MCAO, we performed multiparametric magnetic resonance imaging. We evaluated time courses of cerebral blood flow, apparent diffusion coefficient (ADC), T1, T2, accuracy of infarct prediction strategies, and impact on statistical evaluation of experimental stroke studies. ADC decreased during MCAO but recovered completely on reperfusion after 45 and partially after 90-minute MCAO, followed by a secondary decline. ADC lesion volumes during MCAO or at 6 hours after MCAO largely determined final infarct volumes for 90 but not for 45 minutes MCAO. The majority of chance findings of final infarct volume differences in random group allocations of animals were associated with significant differences in early ADC lesion volumes for 90, but not for 45-minute MCAO. The prediction accuracy of early magnetic resonance imaging for infarct volumes depends on timing of magnetic resonance imaging and MCAO duration. Variability of the posterior communicating artery in C57Bl6 mice contributes to differences in prediction accuracy between short and long MCAO. Early ADC imaging may be used to reduce errors in the interpretation of post MCAO treatment effects on stroke volumes. © 2015 American Heart Association, Inc.

[Effect of ginsenoside Rb1 on cerebral infarction volume and IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion injury model rats].

PubMed

Liu, Jun-Wei; Ren, Ye-Long; Liu, Xu-Ling; Xia, Hong-Lian; Zhang, Hui-Ling; Jin, Shen-Hui; Dai, Qin-Xue; Wang, Jun-Lu

2013-12-01

To investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats. The I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R. In the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05). Ginsenoside Rb1 (20, 40, 80 mg/kg) might effectively release local cerebral ischemia by down-regulating the IL-1 beta expression.

Acute Hyperglycemia Does Not Affect Brain Swelling or Infarction Volume After Middle Cerebral Artery Occlusion in Rats.

PubMed

McBride, Devin W; Matei, Nathanael; Câmara, Justin R; Louis, Jean-Sébastien; Oudin, Guillaume; Walker, Corentin; Adam, Loic; Liang, Xiping; Hu, Qin; Tang, Jiping; Zhang, John H

2016-01-01

Stroke disproportionally affects diabetic and hyperglycemic patients with increased incidence and is associated with higher morbidity and mortality due to brain swelling. In this study, the intraluminal suture middle cerebral artery occlusion (MCAO) model was used to examine the effects of blood glucose on brain swelling and infarct volume in acutely hyperglycemic rats and normo-glycemic controls. Fifty-four rats were distributed into normo-glycemic sham surgery, hyperglycemic sham surgery, normo-glycemic MCAO, and hyperglycemic MCAO. To induce hyperglycemia, 15 min before MCAO surgery, animals were injected with 50 % dextrose. Animals were subjected to 90 min of MCAO and sacrificed 24 h after reperfusion for hemispheric brain swelling and infarct volume calculations using standard equations. While normo-glycemic and hyperglycemic animals after MCAO presented with significantly higher brain swelling and larger infarcts than their respective controls, no statistical difference was observed for either brain swelling or infarct volume between normo-glycemic shams and hyperglycemic shams or normo-glycemic MCAO animals and hyperglycemic MCAO animals. The findings of this study suggest that blood glucose does not have any significant effect on hemispheric brain swelling or infarct volume after MCAO in rats.

[Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction].

PubMed

Strauer, B E; Brehm, M; Zeus, T; Gattermann, N; Hernandez, A; Sorg, R V; Kögler, G; Wernet, P

2001-08-24

The regenerative potential of human autologous adult stem cells on myocardial regeneration and neovascularisation after myocardial infarction may contribute to healing of the infarction area. But no clinical application has previously been reported. We here describe for the first time the results of this method applied in a patient who had sustained an acute myocardial infarction. 14 hours after the onset of left precordial pain a 46-year-old man was admitted to our hospital for interventional diagnosis and treatment. Coronary angiography demonstrated occlusion of the anterior descending branch of the left coronary artery with transmural infarction. This was treated by percutaneous transluminal catheter angioplasty and stent placement. Mononuclear bone marrow cells of the patient were prepared and 6 days after infaction 1,2 infinity 107 cells were transplanted at low pressure via a percutaneous transluminal catheter placed in the infarct-related artery. Before and 10 weeks after this procedure left ventricular function, infarct size, ventricular geometry and myocardial perfusion were measured by (201)thallium SPECT both at rest and on exercise, together with bull's-eye analysis, dobutamine stress echocardiography, right heart catheterisation and radionuclide ventriculography. At 10 weeks after the stem cell transplantation the transmural infarct area had been reduced from 24.6 % to 15.7 % of left ventricular circumference, while ejection fraction, cardiac index and stroke volume had increased by 20-30 %. On exercise the end diastolic volume had decreased by 30 % and there was a comparable fall in left ventricular filling pressure (mean pulmonary capillary pressure). These results for the first time demonstrate that selective intracoronary transplantation of human autologous adult stem cells is possible under clinical conditions and that it can lead to regeneration of the myocardial scar after transmural infarction. The therapeutic effects may be ascribed to stem cell-associated myocardial regeneration and neovascularisation.

Contrast-Enhanced C-arm Computed Tomography Imaging of Myocardial Infarction in the Interventional Suite

PubMed Central

Girard, Erin E; Al-Ahmad, Amin; Rosenberg, Jarrett; Luong, Richard; Moore, Teri; Lauritsch, Günter; Chan, Frandics; Lee, David P.; Fahrig, Rebecca

2014-01-01

Objectives Cardiac C-arm CT uses a standard C-arm fluoroscopy system rotating around the patient to provide CT-like images during interventional procedures without moving the patient to a conventional CT scanner. We hypothesize that C-arm computed tomography (CT) can be used to visualize and quantify the size of perfusion defects and late enhancement resulting from a myocardial infarction (MI) using contrast enhanced techniques similar to previous CT and magnetic resonance imaging studies. Materials and Methods A balloon occlusion followed by reperfusion in a coronary artery was used to study acute and subacute MI in 12 swine. ECG-gated C-arm CT images were acquired the day of infarct creation (n=6) or 4 weeks after infarct creation (n = 6). Images were acquired immediately following contrast injection, then at 1 minute, and every 5 minutes up to 30 minutes with no additional contrast. The volume of the infarct as measured on C-arm CT was compared against pathology. Results The volume of acute MI, visualized as a combined region of hyperenhancement with a hypoenhanced core, correlated well with pathologic staining (concordance correlation = 0.89, p<0.0001, mean difference = 0.67±2.98 cm3). The volume of subacute MI, visualized as a region of hyperenhancement, correlated well with pathologic staining at imaging times 5–15 minutes following contrast injection (concordance correlation = 0.82, p<.001, mean difference = −0.64±1.94 cm3). Conclusions C-arm CT visualization of acute and subacute myocardial infarction is possible in a porcine model but improvement in the imaging technique is important before clinical use. Visualization of MI in the catheterization lab may be possible and could provide 3D images for guidance during interventional procedures. PMID:25635589

[Histopathological changes in human placentas related to hypertensive disorders].

PubMed

Artico, Luciano Guimarães; Madi, José Mauro; Godoy, Alessandra Eifler Guerra; Coelho, Celso Piccoli; Rombaldi, Renato Luís; Artico, Graziela Rech

2009-01-01

to determine the prevalence of histopathological changes, in human placentas, related to hypertensive syndromes. a transversal study that compares histopathological changes identified in 43 placentae from hypertensive pregnant women (HypPr), with the ones from 33 placentae from normotensive pregnant women (NorPr). The weight, volume and macroscopic and microscopic occurrence of infarctions, clots, hematomas, atherosis (partial obliteration, thickness of layers and presence of blood vessels hyalinization) and Tenney-Parker changes (absent, discreet and prominent), as well as the locating of infarctions and clots (central, peripheral or the association of both) have been analyzed. The chi2 and t Student tests have been used for the statistical analysis, as well as medians, standard deviations and ratios. It has been considered as significant, p<0.05. the macroscopic study of HypPr placentae have presented lower weight (461.1 versus 572.1 g) and volume (437.4 versus 542.0 cm(3)), higher infarction (51.2 versus 45.5%; p<0.05: OR=1.15) and clots (51.2 versus 15.1%; p<0.05; OR=5.4) ratios, as compared to the NorPr's. In the HypPr and NorPr, microscopic clots have occurred in 83.7 versus 45.5% (p<0.05; OR=4.3), respectively. Atherosis and Tenney-Parker changes have been statistically associated to the hypertensive syndromes (p<0.05). the obtained data allow us to associate lower placentary weight and volume, higher ratio of macro and microscopic infarction, clots, atherosis and Tenney-Parker changes to placentae of gestations occurring with hypertensive syndromes.

Successful Microbubble Sonothrombolysis without Tissue Plasminogen Activator in a Rabbit Model of Acute Ischemic Stroke

PubMed Central

Culp, William C.; Flores, Rene; Brown, Aliza T.; Lowery, John D.; Roberson, Paula K.; Hennings, Leah J.; Woods, Sean D.; Hatton, Jeff H.; Culp, Benjamin C.; Skinner, Robert D.; Borrelli, Michael J.

2011-01-01

Background Microbubbles (MB) combined with ultrasound (US) have been shown to lyse clots without tissue plasminogen activator (tPA) both in vitro and in vivo. We evaluated sonothrombolysis with three types of MB using a rabbit embolic stroke model. Methods New Zealand White rabbits (n=74) received internal carotid angiographic embolization of single 3 day-old cylindrical clots (0.6×4.0-mm). Groups included: 1) control (n=11) embolized without treatment, 2) tPA (n=20), 3) tPA+US (n=10), 4) Perflutren Lipid MB+US (n=16), 5) albumin 3µm MB+US (n=8), and 6) tagged albumin 3µm MB+US (n=9). Treatment began 1 hour post-embolization. Ultrasound was pulsed-wave (1 MHz; 0.8 W/cm2) for 1 hour; rabbits with tPA received intravenous tPA (0.9 mg/kg) over 1 hour. Lipid MB dose was intravenous (0.16 mg/kg) over 30 minutes. Dosage of 3µm MB was 5×109 MB intravenously alone or tagged with eptifibatide and fibrin antibody over 30 minutes. Rabbits were euthanized at 24 hours. Infarct volume was determined using vital stains on brain sections. Hemorrhage was evaluated on H&E sections. Results Infarct volume percent was lower for rabbits treated with Lipid MB+US (1.0%±0.6%; P=0.013), 3µm MB+US (0.7%±0.9%; P=0.018), and tagged 3µm MB+US (0.8%±0.8%; P=0.019) compared with controls (3.5%±0.8%). The three MB types collectively had lower infarct volumes (P=0.0043) than controls. Infarct volume averaged 2.2%±0.6% and 1.7%±0.8% for rabbits treated with tPA alone and tPA+US, respectively (P=NS). Conclusions Sonothrombolysis without tPA using these MB is effective in decreasing infarct volumes. Study of human application and further MB technique development are justified. PMID:21700942

Tanshinone inhibits neuronal cell apoptosis and inflammatory response in cerebral infarction rat model

PubMed Central

Zhou, Liang; Zhang, Jie; Wang, Chao; Sun, Qiangsan

2017-01-01

We aimed to investigate the effect and mechanisms of tanshinone (TSN) IIA in cerebral infarction. The cerebral infarction rat model was established by middle cerebral artery occlusion (MCAO). After pretreatment with TSN, cerebral infarct volume, cerebral edema, and neurological deficits score were evaluated, as well as cell apoptosis in hippocampus and cortex of the brain was examined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). In addition, rat primary neuronal cells were isolated and cultured in oxygen-glucose deprivation (OGD) conditions. After pretreatment with TSN, cell viability and apoptosis were observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. The expressions of Bax and B-cell lymphoma 2 (Bcl-2) were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. Compared with untreated cerebral infarction rat, TSN treatment significantly reduced cerebral infarct volume, cerebral edema, and neurological deficits score (P < 0.05). Cell apoptosis as well as the levels of IL-6, TNF-α, and CRP in hippocampus and cortex of cerebral infarction rat were inhibited after pretreatment with TSN (P < 0.05). Furthermore, TSN remarkably increased cell viability and inhibited cell apoptosis ratio (P < 0.05) in OGD-induced rat neuronal cells. Besides, TSN significantly downregulated the expression of Bax and upregulated Bcl-2 (P < 0.05). TSN IIA has a preventive effect on cerebral infarction by inhibiting neuronal cell apoptosis and inflammatory response in vitro and in vivo. PMID:28402151

Tanshinone inhibits neuronal cell apoptosis and inflammatory response in cerebral infarction rat model.

PubMed

Zhou, Liang; Zhang, Jie; Wang, Chao; Sun, Qiangsan

2017-06-01

We aimed to investigate the effect and mechanisms of tanshinone (TSN) IIA in cerebral infarction. The cerebral infarction rat model was established by middle cerebral artery occlusion (MCAO). After pretreatment with TSN, cerebral infarct volume, cerebral edema, and neurological deficits score were evaluated, as well as cell apoptosis in hippocampus and cortex of the brain was examined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). In addition, rat primary neuronal cells were isolated and cultured in oxygen-glucose deprivation (OGD) conditions. After pretreatment with TSN, cell viability and apoptosis were observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. The expressions of Bax and B-cell lymphoma 2 (Bcl-2) were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. Compared with untreated cerebral infarction rat, TSN treatment significantly reduced cerebral infarct volume, cerebral edema, and neurological deficits score ( P < 0.05). Cell apoptosis as well as the levels of IL-6, TNF-α, and CRP in hippocampus and cortex of cerebral infarction rat were inhibited after pretreatment with TSN ( P < 0.05). Furthermore, TSN remarkably increased cell viability and inhibited cell apoptosis ratio ( P < 0.05) in OGD-induced rat neuronal cells. Besides, TSN significantly downregulated the expression of Bax and upregulated Bcl-2 ( P < 0.05). TSN IIA has a preventive effect on cerebral infarction by inhibiting neuronal cell apoptosis and inflammatory response in vitro and in vivo.

Plasma bilirubin values on admission and ventricular remodeling after a first anterior ST-segment elevation acute myocardial infarction.

PubMed

Miranda, Berta; Barrabés, José A; Figueras, Jaume; Pineda, Victor; Rodríguez-Palomares, José; Lidón, Rosa-Maria; Sambola, Antonia; Bañeras, Jordi; Otaegui, Imanol; García-Dorado, David

2016-01-01

Bilirubin may elicit cardiovascular protection and heme oxygenase-1 overexpression attenuated post-infarction ventricular remodeling in experimental animals, but the association between bilirubin levels and post-infarction remodeling is unknown. In 145 patients with a first anterior ST-segment elevation acute myocardial infarction (STEMI), we assessed whether plasma bilirubin on admission predicted adverse remodeling (left ventricular end-diastolic volume [LVEDV] increase ≥20% between discharge and 6 months, estimated by magnetic resonance imaging). Patients' baseline characteristics and management were comparable among bilirubin tertiles. LVEDV increased at 6 months (P < 0.001) with respect to the initial exam, but the magnitude of this increase was similar across increasing bilirubin tertiles (10.8 [30.2], 10.1 [22.9], and 12.7 [24.3]%, P = 0.500). Median (25-75 percentile) bilirubin values in patients with and without adverse remodeling were 0.75 (0.60-0.93) and 0.73 (0.60-0.92) mg/dL (P = 0.693). Absence of final TIMI flow grade 3 (odds ratio 3.92, 95% CI 1.12-13.66) and a history of hypertension (2.04, 0.93-4.50), but not admission bilirubin, were independently associated with adverse remodeling. Bilirubin also did not predict the increase in ejection fraction at 6 months. Admission bilirubin values are not related to LVEDV or ejection fraction progression after a first anterior STEMI and do not predict adverse ventricular remodeling. Key messages Bilirubin levels are inversely related to cardiovascular disease, and overexpression of heme oxygenase-1 (the enzyme that determines bilirubin production) has prevented post-infarction ventricular remodeling in experimental animals, but the association between bilirubin levels and the progression of ventricular volumes and function in patients with acute myocardial infarction remained unexplored. In this cohort of patients with a first acute anterior ST-segment elevation myocardial infarction receiving contemporary management, bilirubin levels on admission were not predictive of the changes in left ventricular volumes or ejection fraction at 6 months measured by serial cardiac magnetic resonance imaging. The data are contrary to a significant protective effect of bilirubin against post-infarction ventricular remodeling.

Myocardial Extracellular Volume Estimation by CMR Predicts Functional Recovery Following Acute MI.

PubMed

Kidambi, Ananth; Motwani, Manish; Uddin, Akhlaque; Ripley, David P; McDiarmid, Adam K; Swoboda, Peter P; Broadbent, David A; Musa, Tarique Al; Erhayiem, Bara; Leader, Joshua; Croisille, Pierre; Clarysse, Patrick; Greenwood, John P; Plein, Sven

2017-09-01

In the setting of reperfused acute myocardial infarction (AMI), the authors sought to compare prediction of contractile recovery by infarct extracellular volume (ECV), as measured by T1-mapping cardiac magnetic resonance (CMR), with late gadolinium enhancement (LGE) transmural extent. The transmural extent of myocardial infarction as assessed by LGE CMR is a strong predictor of functional recovery, but accuracy of the technique may be reduced in AMI. ECV mapping by CMR can provide a continuous measure associated with the severity of tissue damage within infarcted myocardium. Thirty-nine patients underwent acute (day 2) and convalescent (3 months) CMR scans following AMI. Cine imaging, tissue tagging, T2-weighted imaging, modified Look-Locker inversion T1 mapping natively and 15 min post-gadolinium-contrast administration, and LGE imaging were performed. The ability of acute infarct ECV and acute transmural extent of LGE to predict convalescent wall motion, ejection fraction (EF), and strain were compared per-segment and per-patient. Per-segment, acute ECV and LGE transmural extent were associated with convalescent wall motion score (p < 0.01; p < 0.01, respectively). ECV had higher accuracy than LGE extent to predict improved wall motion (area under receiver-operating characteristics curve 0.77 vs. 0.66; p = 0.02). Infarct ECV ≤0.5 had sensitivity 81% and specificity 65% for prediction of improvement in segmental function; LGE transmural extent ≤0.5 had sensitivity 61% and specificity 71%. Per-patient, ECV and LGE correlated with convalescent wall motion score (r = 0.45; p < 0.01; r = 0.41; p = 0.02, respectively) and convalescent EF (p < 0.01; p = 0.04). ECV and LGE extent were not significantly correlated (r = 0.34; p = 0.07). In multivariable linear regression analysis, acute infarct ECV was independently associated with convalescent infarct strain and EF (p = 0.03; p = 0.04), whereas LGE was not (p = 0.29; p = 0.24). Acute infarct ECV in reperfused AMI can complement LGE assessment as an additional predictor of regional and global LV functional recovery that is independent of transmural extent of infarction. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke

PubMed Central

Bodhankar, Sheetal; Chen, Yingxin; Vandenbark, Arthur A.; Murphy, Stephanie J.; Offner, Halina

2013-01-01

Clinical stroke induces inflammatory processes leading to cerebral injury. IL-10 expression is elevated during major CNS diseases and limits inflammation in the brain. Recent evidence demonstrated that absence of B-cells led to larger infarct volumes and increased numbers of activated T-cells, monocytes and microglial cells in the brain, thus implicating a regulatory role of B-cell subpopulations in limiting CNS damage from stroke. The aim of this study was to determine whether the IL-10-producing regulatory B-cell subset can limit CNS inflammation and reduce infarct volume following ischemic stroke in B-cell deficient (µMT−/−) mice. Five million IL-10-producing B-cells were obtained from IL-10-GFP reporter mice and transferred i.v. to µMT−/− mice. After 24 h following this transfer, recipients were subjected to 60 min of middle cerebral artery occlusion (MCAO) followed by 48 hours of reperfusion. Compared to vehicle-treated controls, the IL-10+ B-cell-replenished µMT−/− mice had reduced infarct volume and fewer infiltrating activated T-cells and monocytes in the affected brain hemisphere. These effects in CNS were accompanied by significant increases in regulatory T-cells and expression of the co-inhibitory receptor, PD-1, with a significant reduction in the proinflammatory milieu in the periphery. These novel observations provide the first proof of both immunoregulatory and protective functions of IL-10-secreting B-cells in MCAO that potentially could impart significant benefit for stroke patients in the clinic. PMID:23640015

Glatiramer Acetate administration does not reduce damage after cerebral ischemia in mice.

PubMed

Poittevin, Marine; Deroide, Nicolas; Azibani, Feriel; Delcayre, Claude; Giannesini, Claire; Levy, Bernard I; Pocard, Marc; Kubis, Nathalie

2013-01-15

Inflammation plays a key role in ischemic stroke pathophysiology: microglial/macrophage cells and type-1 helper cells (Th1) seem deleterious, while type-2 helper cells (Th2) and regulatory T cells (Treg) seem protective. CD4 Th0 differentiation is modulated by microglial cytokine secretion. Glatiramer Acetate (GA) is an immunomodulatory drug that has been approved for the treatment of human multiple sclerosis by means of a number of mechanisms: reduced microglial activation and pro-inflammatory cytokine production, Th0 differentiation shifting from Th2 to Th2 and Treg with anti-inflammatory cytokine production and increased neurogenesis. We induced permanent (pMCAo) or transient middle cerebral artery occlusion (tMCAo) and GA (2 mg) or vehicle was injected subcutaneously immediately after cerebral ischemia. Mice were sacrificed at D3 to measure neurological deficit, infarct volume, microglial cell density and qPCR of TNFα and IL-1β (pro-inflammatory microglial cytokines), IFNγ (Th2 cytokine), IL-4 (Th2 cytokine), TGFβ and IL-10 (Treg cytokines), and at D7 to evaluate neurological deficit, infarct volume and neurogenesis assessment. We showed that in GA-treated pMCAo mice, infarct volume, microglial cell density and cytokine secretion were not significantly modified at D3, while neurogenesis was enhanced at D7 without significant infarct volume reduction. In GA-treated tMCAo mice, microglial pro-inflammatory cytokines IL-1β and TNFα were significantly decreased without modification of microglial/macrophage cell density, cytokine secretion, neurological deficit or infarct volume at D3, or modification of neurological deficit, neurogenesis or infarct volume at D7. In conclusion, Glatiramer Acetate administered after cerebral ischemia does not reduce infarct volume or improve neurological deficit in mice despite a significant increase in neurogenesis in pMCAo and a microglial pro-inflammatory cytokine reduction in tMCAo. Copyright © 2012 Elsevier B.V. All rights reserved.

Outcomes after endovascular treatment for anterior circulation stroke presenting as wake-up strokes are not different than those with witnessed onset beyond 8 hours.

PubMed

Aghaebrahim, Amin; Leiva-Salinas, Carlos; Jadhav, Ashutosh P; Jankowitz, Brian; Zaidi, Syed; Jumaa, Mouhammad; Urra, Xabi; Amorim, Edilberto; Zhu, Guangming; Giurgiutiu, Dan-Victor; Horev, Anat; Reddy, Vivek; Hammer, Maxim; Wechsler, Lawrence; Wintermark, Max; Jovin, Tudor

2015-12-01

Previous studies have suggested that patients with wake-up stroke (WUS) may have superior outcomes compared with patients with a witnessed late time of onset after revascularization. We sought to test this hypothesis in patients with anterior circulation large vessel occlusion stroke (ACLVOS) treated with endovascular therapy beyond 8 h from time last seen well (TLSW). A single center retrospective review of a prospectively acquired database of consecutive patients was performed to identify patients presenting beyond 8 h of TLSW with radiographic evidence of ACLVOS, small core, and large penumbra who subsequently underwent endovascular treatment. We identified 206 patients. Patients were divided into two groups: (1) patients with WUS (38%, n=78) and (2) patients with witnessed onset beyond 8 h (62%, n=128). The groups were similar in age, baseline National Institutes of Health Stroke Scale score, TLSW to reperfusion, baseline infarct volume, and rate of successful recanalization. Rates of good outcome (modified Rankin Scale score of 0-2 at 90 days, 43% vs. 50%, p=0.3), parenchymal hematoma (9% vs. 5.5%, p=0.3), and final infarct volume (75.2 vs. 61.4 mL, p=0.6) were comparable. Multivariate analysis identified age (OR=0.95, 95% CI 0.91 to 0.99, p<0.042), successful recanalization (OR 6.0, 95% CI 1.5 to 23.5, p=0.009), and final infarct volume (OR 0.98, 95% CI 0.97 to 0.99, p<0.001) but not mode of presentation as predictors of favorable outcomes. Rates of good outcomes, parenchymal hematoma, and final infarct volumes following endovascular treatment may not be different in patients with WUS compared with patients with witnessed onset of symptoms beyond 8 h. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Hospital Volume and 30-Day Mortality for Three Common Medical Conditions

PubMed Central

Ross, Joseph S.; Normand, Sharon-Lise T.; Wang, Yun; Ko, Dennis T.; Chen, Jersey; Drye, Elizabeth E.; Keenan, Patricia S.; Lichtman, Judith H.; Bueno, Héctor; Schreiner, Geoffrey C.; Krumholz, Harlan M.

2010-01-01

Background The association between hospital volume and the death rate for patients who are hospitalized for acute myocardial infarction, heart failure, or pneumonia remains unclear. It is also not known whether a volume threshold for such an association exists. Methods We conducted cross-sectional analyses of data from Medicare administrative claims for all fee-for-service beneficiaries who were hospitalized between 2004 and 2006 in acute care hospitals in the United States for acute myocardial infarction, heart failure, or pneumonia. Using hierarchical logistic-regression models for each condition, we estimated the change in the odds of death within 30 days associated with an increase of 100 patients in the annual hospital volume. Analyses were adjusted for patients’ risk factors and hospital characteristics. Bootstrapping procedures were used to estimate 95% confidence intervals to identify the condition-specific volume thresholds above which an increased volume was not associated with reduced mortality. Results There were 734,972 hospitalizations for acute myocardial infarction in 4128 hospitals, 1,324,287 for heart failure in 4679 hospitals, and 1,418,252 for pneumonia in 4673 hospitals. An increased hospital volume was associated with reduced 30-day mortality for all conditions (P<0.001 for all comparisons). For each condition, the association between volume and outcome was attenuated as the hospital's volume increased. For acute myocardial infarction, once the annual volume reached 610 patients (95% confidence interval [CI], 539 to 679), an increase in the hospital volume by 100 patients was no longer significantly associated with reduced odds of death. The volume threshold was 500 patients (95% CI, 433 to 566) for heart failure and 210 patients (95% CI, 142 to 284) for pneumonia. Conclusions Admission to higher-volume hospitals was associated with a reduction in mortality for acute myocardial infarction, heart failure, and pneumonia, although there was a volume threshold above which an increased condition-specific hospital volume was no longer significantly associated with reduced mortality. PMID:20335587

Comparing a novel automatic 3D method for LGE-CMR quantification of scar size with established methods.

PubMed

Woie, Leik; Måløy, Frode; Eftestøl, Trygve; Engan, Kjersti; Edvardsen, Thor; Kvaløy, Jan Terje; Ørn, Stein

2014-02-01

Current methods for the estimation of infarct size by late-enhanced cardiac magnetic imaging are based upon 2D analysis that first determines the size of the infarction in each slice, and thereafter adds the infarct sizes from each slice to generate a volume. We present a novel, automatic 3D method that estimates infarct size by a simultaneous analysis of all pixels from all slices. In a population of 54 patients with ischemic scars, the infarct size estimated by the automatic 3D method was compared with four established 2D methods. The new 3D method defined scar as the sum of all pixels with signal intensity (SI) ≥35 % of max SI from the complete myocardium, border zone: SI 35-50 % of max SI and core as SI ≥50 % of max SI. The 3D method yielded smaller infarct size (-2.8 ± 2.3 %) and core size (-3.0 ± 1.7 %) than the 2D method most similar to ours. There was no difference in the size of the border zone (0.2 ± 1.4 %). The 3D method demonstrated stronger correlations between scar size and left ventricular (LV) remodelling parameters (LV ejection fraction: r = -0.71, p < 0.0005, LV end-diastolic index: r = 0.54, p < 0.0005, and LV end-systolic index: r = 0.59, p < 0.0005) compared with conventional 2D methods. Infarct size estimation by our novel 3D automatic method is without the need for manual demarcation of the scar; it is less time-consuming and has a stronger correlation with remodelling parameters compared with existing methods.

Multimodal assessment of neuroprotection applied to the use of MK-801 in the endothelin-1 model of transient focal brain ischemia.

PubMed

Moyanova, Slavianka Georgieva; Kortenska, Lidia Vasileva; Mitreva, Rumiana Gesheva; Pashova, Vyara Dincova; Ngomba, Richard Teke; Nicoletti, Ferdinando

2007-06-11

Transient focal ischemia produced by local infusion of endothelin-1 (ET1) in the territory of the middle cerebral artery has been proposed as a potentially useful model for the screening of drugs developed for the treatment of thrombo-embolic stroke. However, most of the data rely exclusively on the assessment of the infarct volume, which is only a partial predictor of the neurological outcome of stroke. Here, we have validated the model using a multimodal approach for the assessment of neuroprotection, which includes (i) determination of the infarct volume by 2,3,5-triphenyltetrazolium chloride staining; (ii) an in-depth behavioral analysis of the neurological deficit; and (iii) an EEG analysis of electrophysiological abnormalities in the peri-infarct somatosensory forelimb cortical area, S1FL. The non-competitive NMDA receptor antagonist, MK-801 (3 mg/kg, injected i.p. 20 min after ET1 infusion in conscious rats) could reduce the infarct volume, reverse the EEG changes occurring at early times post-ET1, and markedly improve the neurological deficit in ischemic animals. The latter effect, however, was visible at day 3 post-ET1, because the drug itself produced substantial behavioral abnormalities at earlier times. We conclude that a multimodal approach can be applied to the ET1 model of focal ischemia, and that MK-801 can be used as a reference compound to which the activity of safer neuroprotective drugs should be compared.

Static cardiomyoplasty with synthetic elastic net suppresses ventricular dilatation and dysfunction after myocardial infarction in the rat: a chronic study.

PubMed

Kato, Nobusuke; Kawaguchi, Akira T; Kishida, Akio; Yamaoka, Tetsuji

2013-07-01

Although static cardiomyoplasty prevents the left ventricle (LV) from dilatation, it may interfere with diastolic relaxation, or cause restriction. We developed a synthetic net with dual elasticity and tested its effect late after myocardial infarction in the rat. LV pressure-volume relationships (PVR) were successively analyzed before, after intravenous volume load, and 10 minutes after occlusion of the left anterior descending artery. Rats were then randomized into groups receiving synthetic net wrapping around the heart (NET+, n = 8) and only partially behind LV (NET-, n = 9), and they underwent the same PVR studies 6 weeks later. End-diastolic and end-systolic PVR were defined, and LV size and function were compared under standardized loading conditions. Although there was no difference in Day 0, increase in LV end-diastolic and end-systolic volumes were significantly attenuated in NET+ rats 6 weeks later when there was a significant correlation between LV volumes by PVR estimation and actual measurements, with significant differences in both measures between the groups: NET+ < NET-. The presence or absence of net did not show restrictive hemodynamics under acute volume load. Static cardiomyoplasty using a synthetic elastic net significantly attenuated LV dilatation and dysfunction without restriction late after myocardial infarction in the rat. © 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Coffee component 3-caffeoylquinic acid increases antioxidant capacity but not polyphenol content in experimental cerebral infarction.

PubMed

Ruiz-Crespo, Silvia; Trejo-Gabriel-Galan, Jose M; Cavia-Saiz, Monica; Muñiz, Pilar

2012-05-01

Although coffee has antioxidant capacity, it is not known which of its bioactive compounds is responsible for it, nor has it been analyzed in experimental cerebral infarction. We studied the effect one of its compounds, 3-caffeoylquinic acid (3-CQA), at doses of 4, 25 and 100 μg on plasma antioxidant capacity and plasma polyphenol content, measuring the differences before and after inducing a cerebral infarction in an experimental rat model. We compared them with 3-caffeoylquinic-free controls. The increase in total antioxidant capacity was only higher than in controls in 3-CQA treated animals with the highest dose. This increase in antioxidant capacity was not due to an increase in polyphenols. No differences between the experimental and control group were found regarding polyphenol content and cerebral infarction volume. In conclusion, this increase in antioxidant capacity in the group that received the highest dose of 3-CQA was not able to reduce experimental cerebral infarction.

Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

PubMed Central

Johnson, Timothy D.; Dittgen, Felix; Nichols, Thomas E.; Malzahn, Uwe; Veltkamp, Roland

2017-01-01

Objective Atrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke. Methods Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke. Results 582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF. Conclusions In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations. PMID:28542605

Rivaroxaban does not influence hemorrhagic transformation in a diabetes ischemic stroke and endovascular thrombectomy model.

PubMed

Liu, Feng-Di; Zhao, Rong; Feng, Xiao-Yan; Shi, Yan-Hui; Wu, Yi-Lan; Shen, Xiao-Lei; Li, Ge-Fei; Liu, Yi-Sheng; Zhao, Ying; He, Xin-Wei; Yin, Jia-Wen; Zhuang, Mei-Ting; Zhao, Bing-Qiao; Liu, Jian-Ren

2018-05-09

Managing endovascular thrombectomy (ET) in diabetic ischemic stroke (IS) with novel anticoagulants is challenging due to putative risk of intracerebral hemorrhage. The study evaluates increased hemorrhagic transformation (HT) risk in Rivaroxaban-treated diabetic rats post ET. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 mg/kg streptozotocin. After 4-weeks, rats were pretreated orally with 30 mg/kg Rivaroxaban/saline; prothrombin time was monitored. IS and ET was induced after 1 h, by thread-induced transient middle cerebral artery occlusion (tMCAO) that mimicked mechanical ET for proximal MCA occlusion at 60 min. After 24 h reperfusion, infarct volumes, HT, blood-brain barrier (BBB) permeability, tight junction at peri-ischemic lesion and matrix metalloproteinase-9 (MMP-9) activity was measured. Diabetic rats seemed to exhibit increased infarct volume and HT at 24 h after ET than normal rats. Infarct volumes and functional outcomes did not differ between Rivaroxaban and diabetic control groups. A significant increase in HT volumes and BBB permeability under Rivaroxaban treatment was not detected. Compared to diabetic control group, neither the occludin expression was remarkably lower in the Rivaroxaban group nor the MMP-9 activity was higher. Together, Rivaroxaban does not increase HT after ET in diabetic rats with proximal MCA occlusion, since Rivaroxaban has fewer effects on post-ischemic BBB permeability.

The function of the left anterior temporal pole: evidence from acute stroke and infarct volume

PubMed Central

Tsapkini, Kyrana; Frangakis, Constantine E.

2011-01-01

The role of the anterior temporal lobes in cognition and language has been much debated in the literature over the last few years. Most prevailing theories argue for an important role of the anterior temporal lobe as a semantic hub or a place for the representation of unique entities such as proper names of peoples and places. Lately, a few studies have investigated the role of the most anterior part of the left anterior temporal lobe, the left temporal pole in particular, and argued that the left anterior temporal pole is the area responsible for mapping meaning on to sound through evidence from tasks such as object naming. However, another recent study indicates that bilateral anterior temporal damage is required to cause a clinically significant semantic impairment. In the present study, we tested these hypotheses by evaluating patients with acute stroke before reorganization of structure–function relationships. We compared a group of 20 patients with acute stroke with anterior temporal pole damage to a group of 28 without anterior temporal pole damage matched for infarct volume. We calculated the average percent error in auditory comprehension and naming tasks as a function of infarct volume using a non-parametric regression method. We found that infarct volume was the only predictive variable in the production of semantic errors in both auditory comprehension and object naming tasks. This finding favours the hypothesis that left unilateral anterior temporal pole lesions, even acutely, are unlikely to cause significant deficits in mapping meaning to sound by themselves, although they contribute to networks underlying both naming and comprehension of objects. Therefore, the anterior temporal lobe may be a semantic hub for object meaning, but its role must be represented bilaterally and perhaps redundantly. PMID:21685458

Comparison of CT perfusion summary maps to early diffusion-weighted images in suspected acute middle cerebral artery stroke.

PubMed

Benson, John; Payabvash, Seyedmehdi; Salazar, Pascal; Jagadeesan, Bharathi; Palmer, Christopher S; Truwit, Charles L; McKinney, Alexander M

2015-04-01

To assess the accuracy and reliability of one vendor's (Vital Images, Toshiba Medical, Minnetonka, MN) automated CT perfusion (CTP) summary maps in identification and volume estimation of infarcted tissue in patients with acute middle cerebral artery (MCA) distribution infarcts. From 1085 CTP examinations over 5.5 years, 43 diffusion-weighted imaging (DWI)-positive patients were included who underwent both CTP and DWI <12 h after symptom onset, with another 43 age-matched patients as controls (DWI-negative). Automated delay-corrected postprocessing software (DC-SVD) generated both infarct "core only" and "core+penumbra" CTP summary maps. Three reviewers independently tabulated Alberta Stroke Program Early CT scores (ASPECTS) of both CTP summary maps and coregistered DWI. Of 86 included patients, 36 had DWI infarct volumes ≤70 ml, 7 had volumes >70 ml, and 43 were negative; the automated CTP "core only" map correctly classified each as >70 ml or ≤70 ml, while the "core+penumbra" map misclassified 4 as >70 ml. There were strong correlations between DWI volume with both summary map-based volumes: "core only" (r=0.93), and "core+penumbra" (r=0.77) (both p<0.0001). Agreement between ASPECTS scores of infarct core on DWI with summary maps was 0.65-0.74 for "core only" map, and 0.61-0.65 for "core+penumbra" (both p<0.0001). Using DWI-based ASPECTS scores as the standard, the accuracy of the CTP-based maps were 79.1-86.0% for the "core only" map, and 83.7-88.4% for "core+penumbra." Automated CTP summary maps appear to be relatively accurate in both the detection of acute MCA distribution infarcts, and the discrimination of volumes using a 70 ml threshold. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Looking for the Ideal Particle: An Experimental Embolization Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Senturk, Cagin, E-mail: caginsenturk@yahoo.co; Cakir, Volkan; Yorukoglu, Kutsal

This study sought to compare the most frequently used embolic particles in an animal model. In 16 New Zealand white rabbits, right renal arteries were embolized using four different embolic particles (polyvinyl alcohol [PVA] particles, 150-250 {mu}m; PVA microspheres [PVAMs], 150-300 {mu}m; Tris-acryl gelatin microspheres [TGMs], 100-300 {mu}m; expanding microspheres [EXMs], 50-100 {mu}m). Quantity of embolic material used, embolization time, and angiographic patterns were documented. Fourteen days later, a control angiography was done to document angiographic recanalization and all animals were sacrificed. Histopathological specimens were analyzed for microscopic appearance and granulometric size of the particles, extravasation of the particles, perivascularmore » inflammation, and neocapillarization. The volume of the infarct area in each kidney was calculated. Results revealed a significantly lesser amount of embolic material used in the EXM group (p = 0.020). The angiographic recanalization rate in the EXM group (100%), compared with the PVA (0%) and TGM (0%) groups, was found to be statistically significant (p = 0.014). Although 75% of the renal arteries embolized with PVAMs were recanalized, this was not found to be statistically significant (p = 0.071). Occlusion levels in the PVA group were more proximal than with any of the microspheres. While there was no extravasation in the TGM group, extravasation rates in the PVA, PVAM, and EXM groups were 50%, 25%, and 75%, respectively. A mild degree of inflammation was noted in the PVA, PVAM, and TGM groups. EXMs caused a moderate degree of inflammation in two kidneys (50%). There was neocapillarization in the vessel lumen in all kidneys in the PVA and PVAM groups. The difference was significant (p = 0.014) compared with the TGM and EXM groups, which did not have any neocapillarization. Regarding infarct area volumes, the difference among the groups was significant (p = 0.022). EXMs caused significantly (p = 0.021) less infarction than the other embolic agents. We conclude that EXMs are less efficient due to a high recanalization rate and lesser volume of infarct compared with the other embolic agents in the rabbit kidney model. The most efficient embolization was seen in kidneys embolized with TGMs.« less

The administration of hydrogen sulphide prior to ischemic reperfusion has neuroprotective effects in an acute stroke model

PubMed Central

Kim, Kyung-Won; Kim, Jeong-Kon; Jeon, Sang-Beom; Jung, Seung-Chae; Choi, Choong-Gon; Kim, Sang-Tae; Kim, Jinil; Ham, Su Jeong; Shim, Woo-Hyun; Sung, Yu Sub; Ha, Hyun Kwon; Choi, Yoonseok

2017-01-01

Emerging evidence has suggested that hydrogen sulfide (H2S) may alleviate the cellular damage associated with cerebral ischemia/reperfusion (I/R) injury. In this study, we assessed using 1H-magnetic resonance imaging/magnetic resonance spectroscopy (1H-MRI/MRS) and histologic analysis whether H2S administration prior to reperfusion has neuroprotective effects. We also evaluated for differences in the effects of H2S treatment at 2 time points. 1H-MRI/MRS data were obtained at baseline, and at 3, 9, and 24 h after ischemia from 4 groups: sham, control (I/R injury), sodium hydrosulfide (NaHS)-30 and NaHS-1 (NaHS delivery at 30 and 1 min before reperfusion, respectively). The total infarct volume and the midline shift at 24 h post-ischemia were lowest in the NaHS-1, followed by the NaHS-30 and control groups. Peri-infarct volume was significantly lower in the NaHS-1 compared to NaHS-30 and control animals. The relative apparent diffusion coefficient (ADC) in the peri-infarct region showed that the NaHS-1 group had significantly lower values compared to the NaHS-30 and control animals and that NaHS-1 rats showed significantly higher relative T2 values in the peri-infarct region compared to the controls. The relative ADC value, relative T2 value, levels of N-acetyl-L-aspartate (NAA), and the NAA, glutamate, and taurine combination score (NGT) in the ischemic core region at 24 h post-ischemia did not differ significantly between the 2 NaHS groups and the control except that the NAA and NGT values were higher in the peri-infarct region of the NaHS-1 animals at 9 h post-ischemia. In the ischemic core and peri-infarct regions, the apoptosis rate was lowest in the NaHS-1 group, followed by the NaHS-30 and control groups. Our results suggest that H2S treatment has neuroprotective effects on the peri-infarct region during the evolution of I/R injury. Furthermore, our findings indicate that the administration of H2S immediately prior to reperfusion produces the highest neuroprotective effects. PMID:29161281

Effects of agmatine on blood-brain barrier stabilization assessed by permeability MRI in a rat model of transient cerebral ischemia.

PubMed

Ahn, S S; Kim, S H; Lee, J E; Ahn, K J; Kim, D J; Choi, H S; Kim, J; Shin, N-Y; Lee, S-K

2015-02-01

BBB disruption after acute ischemic stroke and subsequent permeability increase may be enhanced by reperfusion. Agmatine has been reported to attenuate BBB disruption. Our aim was to evaluate the effects of agmatine on BBB stabilization in a rat model of transient cerebral ischemia by using permeability dynamic contrast-enhanced MR imaging at early stages and subsequently to demonstrate the feasibility of dynamic contrast-enhanced MR imaging for the investigation of new therapies. Thirty-four male Sprague-Dawley rats were subjected to transient MCA occlusion for 90 minutes. Immediately after reperfusion, agmatine (100 mg/kg) or normal saline was injected intraperitoneally into the agmatine-treated group (n = 17) or the control group, respectively. MR imaging was performed after reperfusion. For quantitative analysis, regions of interest were defined within the infarct area, and values for volume transfer constant, rate transfer coefficient, volume fraction of extravascular extracellular space, and volume fraction of blood plasma were obtained. Infarct volume, infarct growth, quantitative imaging parameters, and numbers of factor VIII-positive cells after immunohistochemical staining were compared between control and agmatine-treated groups. Among the permeability parameters, volume transfer constant and volume fraction of extravascular extracellular space were significantly lower in the agmatine-treated group compared with the control group (0.05 ± 0.02 minutes(-1) versus 0.08 ± 0.03 minute(-1), P = .012, for volume transfer constant and 0.12 ± 0.06 versus 0.22 ± 0.15, P = .02 for volume fraction of extravascular extracellular space). Other permeability parameters were not significantly different between the groups. The number of factor VIII-positive cells was less in the agmatine-treated group than in the control group (3-fold versus 4-fold, P = .037). In ischemic stroke, agmatine protects the BBB, which can be monitored in vivo by quantification of permeability by using dynamic contrast-enhanced MR imaging. Therefore, dynamic contrast-enhanced MR imaging may serve as a potential imaging biomarker for assessing the BBB stabilization properties of pharmacologic agents. © 2015 by American Journal of Neuroradiology.

Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia.

PubMed

Li, Jun; Liang, Xibin; Wang, Qian; Breyer, Richard M; McCullough, Louise; Andreasson, Katrin

2008-06-20

Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE(2) receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE(2) EP2, EP3, and EP4 receptors, would reduce brain injury in the murine middle cerebral artery occlusion-reperfusion (MCAO-RP) model. Administration of misoprostol, at the time of MCAO or 2h after MCAO, resulted in significant rescue of infarct volume at 24 and 72h. Immunocytochemistry demonstrated dynamic regulation of the EP2 and EP4 receptors during reperfusion in neurons and endothelial cells of cerebral cortex and striatum, with limited expression of EP3 receptor. EP3-/- mice had no significant changes in infarct volume compared to control littermates. Moreover, administration of misoprostol to EP3+/+ and EP3-/- mice showed similar levels of infarct rescue, indicating that misoprostol protection was not mediated through the EP3 receptor. Taken together, these findings suggest a novel function for misoprostol as a protective agent in cerebral ischemia acting via the PGE(2) EP2 and/or EP4 receptors.

Can prostatic arterial embolisation (PAE) reduce the volume of the peripheral zone? MRI evaluation of zonal anatomy and infarction after PAE.

PubMed

Lin, Yen-Ting; Amouyal, Grégory; Correas, Jean-Michel; Pereira, Héléna; Pellerin, Olivier; Del Giudice, Costantino; Déan, Carole; Thiounn, Nicolas; Sapoval, Marc

2016-10-01

To assess the impact of prostatic arterial embolisation (PAE) on various prostate gland anatomical zones. We retrospectively reviewed paired MRI scans obtained before and after PAE for 25 patients and evaluated changes in volumes of the median lobe (ML), central gland (CG), peripheral zone (PZ) and whole prostate gland (WPV) following PAE. We used manual segmentation to calculate volume on axial view T2-weighted images for ML, CG and WPV. We calculated PZ volume by subtracting CG volume from WPV. Enhanced phase on dynamic contrasted-enhanced MRI was used to evaluate the infarction areas after PAE. Clinical results of International Prostate Symptom Score and International Index of Erectile Function questionnaires and the urodynamic study were evaluated before and after PAE. Significant reductions in volume were observed after PAE for ML (26.2 % decrease), CG (18.8 %), PZ (16.4 %) and WPV (19.1 %; p < 0.001 for all these volumes). Patients with clinical failure had smaller volume reductions for WPV, ML and CG (all p < 0.05). Patients with significant CG infarction after PAE displayed larger WPV, ML and CG volume reductions (all p < 0.01). PAE can significantly decrease WPV, ML, CG and PZ volumes, and poor clinical outcomes are associated with smaller volume reductions. • The MRI segmentation method provides detailed comparisons of prostate volume change. • Prostatic arterial embolisation (PAE) decreased central gland and peripheral zone volumes. • Prostates with infarction after PAE showed larger decreases in volume. • A larger decrease in prostate volume is associated with clinical success.

Morphological MRI characteristics of recent small subcortical infarcts.

PubMed

Gattringer, Thomas; Eppinger, Sebastian; Pinter, Daniela; Pirpamer, Lukas; Berghold, Andrea; Wünsch, Gerit; Ropele, Stefan; Wardlaw, Joanna M; Enzinger, Christian; Fazekas, Franz

2015-10-01

New imaging criteria for recent small subcortical infarcts have recently been proposed, replacing the earlier term 'lacunar infarction', but their applicability and impact on lesion selection is yet unknown. To collect information on the morphologic characteristics and variability of recent small subcortical infarcts on magnetic resonance imaging in regard to lesion location and demographic variables. We identified all patients with acute stroke and cerebral magnetic resonance imaging from 2008 to 2013 in our hospital database and selected those with a single recent small subcortical infarct defined by an estimated maximal axial diameter of 20 mm. Recent small subcortical infarcts were segmented on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence to calculate the largest axial and longitudinal diameter and lesion volume. We assessed morphometric differences of recent small subcortical infarcts regarding location and demographic variables and the impact of different recent small subcortical infarct definitions on lesion selection. Three hundred forty-four patients (median age 72; range 25-92 years, 65% male) were selected. Most recent small subcortical infarcts were located in the basal ganglia (n = 111), followed by pons (n = 92), thalamus (n = 77), and centrum semiovale (n = 64). Quantitative measurements confirmed visual assessment of the axial diameter in 95%. All morphometric variables were strongly intercorrelated and comparable on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence. Recent small subcortical infarcts in the basal ganglia were significantly larger both in the axial and longitudinal direction compared with other regions. Dichotomization of recent small subcortical infarcts according to axial (≤ / >15 mm) or longitudinal (≤ / >20 mm) sizes resulted in different regional frequencies and distributions. Age, gender, and time from stroke onset to magnetic resonance imaging did not influence lesion metrics or the distribution of recent small subcortical infarcts. Our study confirms the recent neuroimaging criteria for recent small subcortical infarcts as a practical concept. Definitions of the maximal axial and longitudinal diameter have a significant impact on the frequency and distribution of selected infarcts, which has to be considered for future studies. © 2015 World Stroke Organization.

Dynamic susceptibility contrast-enhanced perfusion MR imaging at 1.5 T predicts final infarct size in a rat stroke model.

PubMed

Chen, Feng; Suzuki, Yasuhiro; Nagai, Nobuo; Peeters, Ronald; Marchal, Guy; Ni, Yicheng

2005-01-30

The purpose of the present animal experiment was to determine whether source images from dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) at a 1.5T MR scanner, performed early after photochemically induced thrombosis (PIT) of cerebral middle artery (MCA), is feasible to predict final cerebral infarct size in a rat stroke model. Fifteen rats were subjected to PIT of proximal MCA. T2 weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced PWI were obtained at 1 h and 24 h after MCA occlusion. The relative lesion size (RLS) was defined as lesion volume/brain volume x 100% and measured for MR images, and compared with the final RLS on the gold standard triphenyl tetrazolium chloride (TTC) staining at 24 h. One hour after MCA occlusion, the RLS with DSC-PWI was 24.9 +/- 6.3%, which was significantly larger than 17.6 +/- 4.8% with DWI (P < 0.01). At 24 h, the final RLS on TTC was 24.3 +/- 4.8%, which was comparable to 25.1 +/- 3.5%, 24.6 +/- 3.6% and 27.9 +/- 6.8% with T2WI, DWI and DSC-PWI respectively (P > 0.05). The fact that at 1 h after MCA occlusion only the displayed perfusion deficit was similar to the final infarct size on TTC (P > 0.05) suggests that early source images from DSC-PWI at 1.5T MR scanner is feasible to noninvasively predict the final infarct size in rat models of stroke.

Differential MR Delayed Enhancement Patterns of Chronic Myocardial Infarction between Extracellular and Intravascular Contrast Media

PubMed Central

Wang, Jian; Xiang, Bo; Lin, Hung Yu; Liu, Hongyu; Freed, Darren; Arora, Rakesh C.; Tian, Ganghong

2015-01-01

Objectives Because the distribution volume and mechanism of extracellular and intravascular MR contrast media differ considerably, the enhancement pattern of chronic myocardial infarction with extracellular or intravascular media might also be different. This study aims to investigate the differences in MR enhancement patterns of chronic myocardial infarction between extracellular and intravascular contrast media. Materials and Methods Twenty pigs with myocardial infarction underwent cine MRI, first pass perfusion MRI and delayed enhancement MRI with extracellular or intravascular media at four weeks after coronary occlusion. Myocardial blood flow (MBF) was determined with microsphere measurement. The infarction histopathological changes were evaluated by hematoxylin and eosin staining and Masson's trichrome method. Results Cine MRI revealed the reduced wall thickening in chronic infarction compared with normal myocardium. Moreover, significant wall thinning in chronic infarction was observed in cine MRI. Peak first-pass signal intensity didn’t significantly differ between chronic infarction and normal myocardium no matter what kinds of contrast media. At the following delayed enhancement phase, extracellular media-enhanced signal intensity was significantly higher in chronic infarction than in normal myocardium. Conversely, intravascular media-enhanced signal intensity was almost equivalent among chronic infarction and normal myocardium. At four weeks after infarction, MBF in chronic infarction approached to that in normal myocardium. Large thick-walled vessels were detected at peri-infarction zones. The cardiomyocytes were replaced by scar tissue consisting of dilated blood vessels and discrete fibers of collagen. Conclusions Chronic infarction was characterized by the significantly reduced wall thickening and the definite wall thinning. First-pass myocardial perfusion defect was not detected in chronic infarction with two media due to the significantly recovered MBF and well-developed collateral vessels. Infarction remodeling enlarged the extracellular compartment, which was available for extracellular media but not accessible to intravascular media. Extracellular media identified chronic infarction as the hyper-enhancement; nonetheless, intravascular media didn’t provide delayed enhancement. PMID:25816056

3D cardiac wall thickening assessment for acute myocardial infarction

NASA Astrophysics Data System (ADS)

Khalid, A.; Chan, B. T.; Lim, E.; Liew, Y. M.

2017-06-01

Acute myocardial infarction (AMI) is the most severe form of coronary artery disease leading to localized myocardial injury and therefore irregularities in the cardiac wall contractility. Studies have found very limited differences in global indices (such as ejection fraction, myocardial mass and volume) between healthy subjects and AMI patients, and therefore suggested regional assessment. Regional index, specifically cardiac wall thickness (WT) and thickening is closely related to cardiac function and could reveal regional abnormality due to AMI. In this study, we developed a 3D wall thickening assessment method to identify regional wall contractility dysfunction due to localized myocardial injury from infarction. Wall thickness and thickening were assessed from 3D personalized cardiac models reconstructed from cine MRI images by fitting inscribed sphere between endocardial and epicardial wall. The thickening analysis was performed in 5 patients and 3 healthy subjects and the results were compared against the gold standard 2D late-gadolinium-enhanced (LGE) images for infarct localization. The notable finding of this study is the highly accurate estimation and visual representation of the infarct size and location in 3D. This study provides clinicians with an intuitive way to visually and qualitatively assess regional cardiac wall dysfunction due to infarction in AMI patients.

[Imaging Observation of Scalp Acupuncture on Brain Gray Matter Injury in Stroke Patients with Cerebral Infarction].

PubMed

Lang, Yi; Cui, Fang-yuan; Li, Kuang-shi; Tan, Zhong-jian; Zou, Yi-huai

2016-03-01

To study features of brain gray matter injury in cerebral infarction patients and intervention of scalp acupuncture by using voxel-based morphology. A total of 16 cerebral infarction patients were recruited in this study, and assigned to the scalp acupuncture group and the control group, 8 in each group. Another 16 healthy volunteers were recruited as a normal group. All patients received scanning of T1 structure. Images were managed using VBM8 Software package. Difference of the gray matter structure was compared among the scalp acupuncture group, the control group, and the healthy volunteers. Compared with healthy volunteers, gray matter injury of cerebral infarction patients mainly occurred in 14 brain regions such as cingulate gyrus, precuneus, cuneus, anterior central gyrus, insular lobe, and so on. They were mainly distributed in affected side. Two weeks after treatment when compared with healthy volunteers, gray matter injury of cerebral infarction patients in the scalp acupuncture group still existed in 8 brain regions such as bilateral lingual gyrus, posterior cingulate gyrus, left cuneus, right precuneus, and so on. New gray matter injury occurred in lingual gyrus and posterior cingulate gyrus. Two weeks after treatment when compared with healthy volunteers, gray matter injury of cerebral infarction patients in the control group existed in 23 brain regions: bilateral anterior cingulum, caudate nucleus, cuneate lobe, insular lobe, inferior frontal gyrus, medial frontal gyrus, precuneus, paracentral lobule, superior temporal gyrus, middle temporal gyrus, lingual gyrus, right postcentral gyrus, posterior cingulate gyrus, precentral gyrus, middle frontal gyrus, and so on. New gray matter injury still existed in 9 cerebral regions such as lingual gyrus, posterior cingulate gyrus, postcentral gyrus, and so on. Brain gray matter structure is widely injured after cerebral infarction. Brain gray matter volume gradually decreased as time went by. Combined use of scalp acupuncture might inhibit the progression of gray matter injury more effectively.

Retrospective Analysis of Radiological Recurrence Patterns in Glioblastoma, Their Prognostic Value And Association to Postoperative Infarct Volume.

PubMed

Bette, Stefanie; Barz, Melanie; Huber, Thomas; Straube, Christoph; Schmidt-Graf, Friederike; Combs, Stephanie E; Delbridge, Claire; Gerhardt, Julia; Zimmer, Claus; Meyer, Bernhard; Kirschke, Jan S; Boeckh-Behrens, Tobias; Wiestler, Benedikt; Gempt, Jens

2018-03-14

Recent studies suggested that postoperative hypoxia might trigger invasive tumor growth, resulting in diffuse/multifocal recurrence patterns. Aim of this study was to analyze distinct recurrence patterns and their association to postoperative infarct volume and outcome. 526 consecutive glioblastoma patients were analyzed, of which 129 met our inclusion criteria: initial tumor diagnosis, surgery, postoperative diffusion-weighted imaging and tumor recurrence during follow-up. Distinct patterns of contrast-enhancement at initial diagnosis and at first tumor recurrence (multifocal growth/progression, contact to dura/ventricle, ependymal spread, local/distant recurrence) were recorded by two blinded neuroradiologists. The association of radiological patterns to survival and postoperative infarct volume was analyzed by uni-/multivariate survival analyses and binary logistic regression analysis. With increasing postoperative infarct volume, patients were significantly more likely to develop multifocal recurrence, recurrence with contact to ventricle and contact to dura. Patients with multifocal recurrence (Hazard Ratio (HR) 1.99, P = 0.010) had significantly shorter OS, patients with recurrent tumor with contact to ventricle (HR 1.85, P = 0.036), ependymal spread (HR 2.97, P = 0.004) and distant recurrence (HR 1.75, P = 0.019) significantly shorter post-progression survival in multivariate analyses including well-established prognostic factors like age, Karnofsky Performance Score (KPS), therapy, extent of resection and patterns of primary tumors. Postoperative infarct volume might initiate hypoxia-mediated aggressive tumor growth resulting in multifocal and diffuse recurrence patterns and impaired survival.

Digital map of posterior cerebral artery infarcts associated with posterior cerebral artery trunk and branch occlusion.

PubMed

Phan, Thanh G; Fong, Ashley C; Donnan, Geoffrey; Reutens, David C

2007-06-01

Knowledge of the extent and distribution of infarcts of the posterior cerebral artery (PCA) may give insight into the limits of the arterial territory and infarct mechanism. We describe the creation of a digital atlas of PCA infarcts associated with PCA branch and trunk occlusion by magnetic resonance imaging techniques. Infarcts were manually segmented on T(2)-weighted magnetic resonance images obtained >24 hours after stroke onset. The images were linearly registered into a common stereotaxic coordinate space. The segmented images were averaged to yield the probability of involvement by infarction at each voxel. Comparisons were made with existing maps of the PCA territory. Thirty patients with a median age of 61 years (range, 22 to 86 years) were studied. In the digital atlas of the PCA, the highest frequency of infarction was within the medial temporal lobe and lingual gyrus (probability=0.60 to 0.70). The mean and maximal PCA infarct volumes were 55.1 and 128.9 cm(3), respectively. Comparison with published maps showed greater agreement in the anterior and medial boundaries of the PCA territory compared with its posterior and lateral boundaries. We have created a probabilistic digital atlas of the PCA based on subacute magnetic resonance scans. This approach is useful for establishing the spatial distribution of strokes in a given cerebral arterial territory and determining the regions within the arterial territory that are at greatest risk of infarction.

Ischemic lesion volume determination on diffusion weighted images vs. apparent diffusion coefficient maps.

PubMed

Bråtane, Bernt Tore; Bastan, Birgul; Fisher, Marc; Bouley, James; Henninger, Nils

2009-07-07

Though diffusion weighted imaging (DWI) is frequently used for identifying the ischemic lesion in focal cerebral ischemia, the understanding of spatiotemporal evolution patterns observed with different analysis methods remains imprecise. DWI and calculated apparent diffusion coefficient (ADC) maps were serially obtained in rat stroke models (MCAO): permanent, 90 min, and 180 min temporary MCAO. Lesion volumes were analyzed in a blinded and randomized manner by 2 investigators using (i) a previously validated ADC threshold, (ii) visual determination of hypointense regions on ADC maps, and (iii) visual determination of hyperintense regions on DWI. Lesion volumes were correlated with 24 hour 2,3,5-triphenyltetrazoliumchloride (TTC)-derived infarct volumes. TTC-derived infarct volumes were not significantly different from the ADC and DWI-derived lesion volumes at the last imaging time points except for significantly smaller DWI lesions in the pMCAO model (p=0.02). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived lesions on ADC maps than DWI (p<0.05). Following reperfusion, lesion volumes on the ADC maps significantly reduced but no change was observed on DWI. Visually determined lesion volumes on ADC maps and DWI by both investigators correlated significantly with threshold-derived lesion volumes on ADC maps with the former method demonstrating a stronger correlation. There was also a better interrater agreement for ADC map analysis than for DWI analysis. Ischemic lesion determination by ADC was more accurate in final infarct prediction, rater independent, and provided exclusive information on ischemic lesion reversibility.

Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice.

PubMed

Hilal, Rose; Poittevin, Marine; Pasteur-Rousseau, Adrien; Cogo, Adrien; Mangin, Gabrielle; Chevauché, Marie; Ziat, Yasmine; Vilar, José; Launay, Jean-Marie; Gautier, Jean-François; Broquères-You, Dong; Levy, Bernard I; Merkulova-Rainon, Tatyana; Kubis, Nathalie

2018-01-01

Clinical trials of cell therapy in stroke favor autologous cell transplantation. To date, feasibility studies have used bone marrow-derived mononuclear cells, but harvesting bone marrow cells is invasive thus complicating bedside treatment. We investigated the therapeutic potential of peripheral blood-derived mononuclear cells (PB-MNC) harvested from diabetic patients and stimulated by ephrin-B2 (PB-MNC+) (500,000 cells), injected intravenously 18-24 hours after induced cerebral ischemia in mice. Infarct volume, neurological deficit, neurogenesis, angiogenesis, and inflammation were investigated as were the potential mechanisms of PB-MNC+ cells in poststroke neurorepair. At D3, infarct volume was reduced by 60% and 49% compared to unstimulated PB-MNC and PBS-treated mice, respectively. Compared to PBS, injection of PB-MNC+ increased cell proliferation in the peri-infarct area and the subventricular zone, decreased microglia/macrophage cell density, and upregulated TGF- β expression. At D14, microvessel density was decreased and functional recovery was enhanced compared to PBS-treated mice, whereas plasma levels of BDNF, a major regulator of neuroplasticity, were increased in mice treated with PB-MNC+ compared to the other two groups. Cell transcriptional analysis showed that ephrin-B2 induced phenotype switching of PB-MNC by upregulating genes controlling cell proliferation, inflammation, and angiogenesis, as confirmed by adhesion and Matrigel assays. Conclusions . This feasibility study suggests that PB-MNC+ transplantation poststroke could be a promising approach but warrants further investigation. If confirmed, this rapid, noninvasive bedside cell therapy strategy could be applied to stroke patients at the acute phase.

Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice

PubMed Central

Hilal, Rose; Poittevin, Marine; Pasteur-Rousseau, Adrien; Cogo, Adrien; Mangin, Gabrielle; Chevauché, Marie; Ziat, Yasmine; Vilar, José; Launay, Jean-Marie; Gautier, Jean-François; Broquères-You, Dong; Levy, Bernard I.; Merkulova-Rainon, Tatyana

2018-01-01

Clinical trials of cell therapy in stroke favor autologous cell transplantation. To date, feasibility studies have used bone marrow-derived mononuclear cells, but harvesting bone marrow cells is invasive thus complicating bedside treatment. We investigated the therapeutic potential of peripheral blood-derived mononuclear cells (PB-MNC) harvested from diabetic patients and stimulated by ephrin-B2 (PB-MNC+) (500,000 cells), injected intravenously 18–24 hours after induced cerebral ischemia in mice. Infarct volume, neurological deficit, neurogenesis, angiogenesis, and inflammation were investigated as were the potential mechanisms of PB-MNC+ cells in poststroke neurorepair. At D3, infarct volume was reduced by 60% and 49% compared to unstimulated PB-MNC and PBS-treated mice, respectively. Compared to PBS, injection of PB-MNC+ increased cell proliferation in the peri-infarct area and the subventricular zone, decreased microglia/macrophage cell density, and upregulated TGF-β expression. At D14, microvessel density was decreased and functional recovery was enhanced compared to PBS-treated mice, whereas plasma levels of BDNF, a major regulator of neuroplasticity, were increased in mice treated with PB-MNC+ compared to the other two groups. Cell transcriptional analysis showed that ephrin-B2 induced phenotype switching of PB-MNC by upregulating genes controlling cell proliferation, inflammation, and angiogenesis, as confirmed by adhesion and Matrigel assays. Conclusions. This feasibility study suggests that PB-MNC+ transplantation poststroke could be a promising approach but warrants further investigation. If confirmed, this rapid, noninvasive bedside cell therapy strategy could be applied to stroke patients at the acute phase. PMID:29736174

Degree of Vascular Encasement in Sphenoid Wing Meningiomas Predicts Postoperative Ischemic Complications.

PubMed

McCracken, D Jay; Higginbotham, Raymond A; Boulter, Jason H; Liu, Yuan; Wells, John A; Halani, Sameer H; Saindane, Amit M; Oyesiku, Nelson M; Barrow, Daniel L; Olson, Jeffrey J

2017-06-01

Sphenoid wing meningiomas (SWMs) can encase arteries of the circle of Willis, increasing their susceptibility to intraoperative vascular injury and severe ischemic complications. To demonstrate the effect of circumferential vascular encasement in SWM on postoperative ischemia. A retrospective review of 75 patients surgically treated for SWM from 2009 to 2015 was undertaken to determine the degree of circumferential vascular encasement (0°-360°) as assessed by preoperative magnetic resonance imaging (MRI). A novel grading system describing "maximum" and "total" arterial encasement scores was created. Postoperative MRIs were reviewed for total ischemia volume measured on sequential diffusion-weighted images. Of the 75 patients, 89.3% had some degree of vascular involvement with a median maximum encasement score of 3.0 (2.0-3.0) in the internal carotid artery (ICA), M1, M2, and A1 segments; 76% of patients had some degree of ischemia with median infarct volume of 3.75 cm 3 (0.81-9.3 cm 3 ). Univariate analysis determined risk factors associated with larger infarction volume, which were encasement of the supraclinoid ICA ( P < .001), M1 segment ( P < .001), A1 segment ( P = .015), and diabetes ( P = .019). As the maximum encasement score increased from 1 to 5 in each of the significant arterial segments, so did mean and median infarction volume ( P < .001). Risk for devastating ischemic injury >62 cm 3 was found when the ICA, M1, and A1 vessels all had ≥360° involvement ( P = .001). Residual tumor was associated with smaller infarct volumes ( P = .022). As infarction volume increased, so did modified Rankin Score at discharge ( P = .025). Subtotal resection should be considered in SWM with significant vascular encasement of proximal arteries to limit postoperative ischemic complications. Copyright © 2017 by the Congress of Neurological Surgeons

Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats.

PubMed

Wang, Na; Guo, Qu-lian; Ye, Zhi; Xia, Ping-ping; Wang, E; Yuan, Ya-jing

2011-07-05

Several studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats. Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-α (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining. The rats in the I/R group had lower NDSs (P < 0.05), larger infarct volume (P < 0.05), lower HMGB1 levels (P < 0.05), and higher TNF-α levels (P < 0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P < 0.05). Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.

Microvascular basis for growth of small infarcts following occlusion of single penetrating arterioles in mouse cortex

PubMed Central

Taylor, Zachary J; Hui, Edward S; Watson, Ashley N; Nie, Xingju; Deardorff, Rachael L; Jensen, Jens H; Helpern, Joseph A

2015-01-01

Small cerebral infarcts, i.e. microinfarcts, are common in the aging brain and linked to vascular cognitive impairment. However, little is known about the acute growth of these minute lesions and their effect on blood flow in surrounding tissues. We modeled microinfarcts in the mouse cortex by inducing photothrombotic clots in single penetrating arterioles. The resultant hemodynamic changes in tissues surrounding the occluded vessel were then studied using in vivo two-photon microscopy. We were able to generate a spectrum of infarct volumes by occluding arterioles that carried a range of blood fluxes. Those resulting from occlusion of high-flux penetrating arterioles (flux of 2 nL/s or higher) exhibited a radial outgrowth that encompassed unusually large tissue volumes. The gradual expansion of these infarcts was propagated by an evolving insufficiency in capillary flow that encroached on territories of neighboring penetrating arterioles, leading to the stagnation and recruitment of their perfusion domains into the final infarct volume. Our results suggest that local collapse of microvascular function contributes to tissue damage incurred by single penetrating arteriole occlusions in mice, and that a similar mechanism may add to pathophysiology induced by microinfarcts of the human brain. PMID:26661182

Sevoflurane postconditioning against cerebral ischemic neuronal injury is abolished in diet-induced obesity: role of brain mitochondrial KATP channels.

PubMed

Yang, Zecheng; Chen, Yunbo; Zhang, Yan; Jiang, Yi; Fang, Xuedong; Xu, Jingwei

2014-03-01

Obesity is associated with increased infarct volumes and adverse outcomes following ischemic stroke. However, its effect on anesthetic postconditioning‑induced neuroprotection has not been investigated. The present study examined the effect of sevoflurane postconditioning on focal ischemic brain injury in diet‑induced obesity. Sprague‑Dawley rats were fed a high‑fat diet (HF; 45% kcal as fat) for 12 weeks to develop obesity syndrome. Rats fed a low‑fat diet (LF; 10% kcal as fat) served as controls. The HF or LF‑fed rats were subjected to focal cerebral ischemia for 60 min, followed by 24 h of reperfusion. Postconditioning was performed by exposure to sevoflurane for 15 min immediately at the onset of reperfusion. The involvement of the mitochondrial KATP (mitoKATP) channel was analyzed by the administration of a selective inhibitor of 5‑hydroxydecanoate (5‑HD) prior to sevoflurane postconditioning or by administration of diazoxide (DZX), a mitoKATP channel opener, instead of sevoflurane. The cerebral infarct volume, neurological score and motor coordination were evaluated 24 h after reperfusion. The HF‑fed rats had larger infarct volumes, and lower neurological scores than the LF‑fed rats and also failed to respond to neuroprotection by sevoflurane or DZX. By contrast, sevoflurane and DZX reduced the infarct volumes and improved the neurological scores and motor coordination in the LF‑fed rats. Pretreatment with 5‑HD inhibited sevoflurane‑induced neuroprotection in the LF‑fed rats, whereas it had no effect in the HF‑fed rats. Molecular studies demonstrated that the expression of Kir6.2, a significant mitoKATP channel component, was reduced in the brains of the HF‑fed rats compared with the LF‑fed rats. The results of this study indicate that diet‑induced obesity eliminates the ability of anesthetic sevoflurane postconditioning to protect the brain against cerebral ischemic neuronal injury, most likely due to an impaired brain mitoKATP channel.

Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R.

PubMed

Li, Wei; Suwanwela, Nijasri C; Patumraj, Suthiluk

2016-07-01

Oxidation, inflammation, and apoptosis are three critical factors for the pathogenic mechanism of cerebral ischemia/reperfusion (I/R) injury. Curcumin exhibits substantial biological properties via anti-oxidation, anti-inflammation and anti-apoptotic effects; however, the molecular mechanism underlying the effects of curcumin against cerebral I/R injury remains unclear. To investigate the effects of curcumin on cerebral I/R injury associated with water content, infarction volume, and the expression of nuclear factor-kappa-B (NF-κB) and nuclear factor-erythroid-related factor-2 (Nrf2). Middle cerebral artery occlusion (MCAO, 1-hour occlusion and 24-hour reperfusion) was performed in male Wistar rats (n=64) as a cerebral I/R injury model. In the MCAO+CUR group, the rats were administered curcumin (300mg/kg BW, i.p.) at 30min after occlusion. The same surgical procedures were performed in SHAM rats without MCAO occlusion. At 24h post-operation, the parameters, including neurological deficit scores, blood brain barrier (BBB) disruption, water content, and infarction volume, were determined. Brain tissue NF-κB and Nrf2 expression levels were assayed through immunohistochemistry. Compared with the SHAM group, BBB disruption, neurological deficit, and increased brain water content and infarction volume were markedly demonstrated in the MCAO group. NF-κB expression was enhanced in the MCAO group. However, in the MCAO+CUR group, the upregulation of Nrf2, an anti-oxidation related protein, was consistent with a significant decline in the water content, infarction volume, and NF-κB expression. The protective effects of curcumin against cerebral I/R injury reflect anti-oxidation, anti-inflammation and anti-apoptotic activities, resulting in the elevation of Nrf2 and down-regulation of NF-κB. Copyright © 2015 Elsevier Inc. All rights reserved.

N1-Nonyl-1,4-diaminobutane ameliorates brain infarction size in photochemically induced thrombosis model mice.

PubMed

Masuko, Takashi; Takao, Koichi; Samejima, Keijiro; Shirahata, Akira; Igarashi, Kazuei; Casero, Robert A; Kizawa, Yasuo; Sugita, Yoshiaki

2018-04-13

Inhibitors for polyamine oxidizing enzymes, spermine oxidase (SMOX) and N 1 -acetylpolyamine oxidase (PAOX), were designed and evaluated for their effectiveness in a photochemically induced thrombosis (PIT) mouse model. N 1 -Nonyl-1,4-diaminobutane (C9-4) and N 1 -tridecyl-1,4-diaminobutane (C13-4) competitively inhibited the activity of PAOX and SMOX in a manner comparable to N 1 ,N 4 -bis(2,3-butadienyl)-1,4-butanediamine (MDL72527), an irreversible inhibitor of both enzymes. The two compounds were then tested for their effects in the PIT model. Both intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of C9-4 decreased infarct volumes significantly. By contrast, C13-4 reduced the volume of brain infarction by i.c.v. administration, but no reduction was observed after i.p. administration. C9-4 administered by i.p. injection reduced the volume of brain infarction significantly at doses of more than 3 mg/kg, and the dosage of 5 mg/kg or 10 mg/kg demonstrated the most potent effect and were more effective than equivalent doses of the other inhibitors such as MDL72527 and N-benzylhydroxylamine. I.P. injection of 5 mg/kg of C9-4 provided a therapeutic time window of longer than 12 h. This report demonstrates that C9-4 is a potent inhibitor of the polyamine oxidizing enzymes and is useful lead compound for candidate drugs with a long therapeutic time window, to be used in the treatment of ischemic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Apixaban decreases brain thrombin activity in a male mouse model of acute ischemic stroke.

PubMed

Bushi, Doron; Chapman, Joab; Wohl, Anton; Stein, Efrat Shavit; Feingold, Ekaterina; Tanne, David

2018-05-14

Factor Xa (FXa) plays a critical role in the coagulation cascade by generation of thrombin. During focal ischemia thrombin levels increase in the brain tissue and cause neural damage. This study examined the hypothesis that administration of the FXa inhibitor, apixaban, following focal ischemic stroke may have therapeutic potential by decreasing brain thrombin activity and infarct volume. Male mice were divided into a treated groups that received different doses of apixaban (2, 20, 100 mg/kg administered I.P.) or saline (controls) immediately after blocking the middle cerebral artery (MCA). Thrombin activity was measured by a fluorescence assay on fresh coronal slices taken from the mice brains 24 hr following the MCA occlusion. Infarct volume was assessed using triphenyltetrazolium chloride staining. A high dose of apixaban (100 mg/kg) significantly decreased thrombin activity levels in the ipsilateral hemisphere compared to the control group (Slice#5, p = .016; Slice#6, p = .016; Slice#7, p = .016; Slice#8, p = .036; by the nonparametric Mann-Whitney test). In addition, treatment with apixaban doses of both 100 mg/kg (32 ± 8% vs. 76 ± 7% in the treatment vs. control groups respectively; p = .005 by the nonparametric Mann-Whitney test) and 20 mg/kg (43 ± 7% vs. 76 ± 7% in the treatment vs. control groups respectively; p = .019 by the nonparametric Mann-Whitney test) decreased infarct volumes in areas surrounding the ischemic core (Slices #3 and #8). No brain hemorrhages were observed either in the treated or control groups. In summary, I.P. administration of high dose of apixaban immediately after MCA occlusion decreases brain thrombin activity and reduces infarct size. © 2018 Wiley Periodicals, Inc.

Comparison of hospital variation in acute myocardial infarction care and outcome between Sweden and United Kingdom: population based cohort study using nationwide clinical registries.

PubMed

Chung, Sheng-Chia; Sundström, Johan; Gale, Chris P; James, Stefan; Deanfield, John; Wallentin, Lars; Timmis, Adam; Jernberg, Tomas; Hemingway, Harry

2015-08-07

To assess the between hospital variation in use of guideline recommended treatments and clinical outcomes for acute myocardial infarction in Sweden and the United Kingdom. Population based longitudinal cohort study using nationwide clinical registries. Nationwide registry data comprising all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART/RIKS-HIA, n=87; 119,786 patients) and the UK (NICOR/MINAP, n=242; 391,077 patients), 2004-10. Between hospital variation in 30 day mortality of patients admitted with acute myocardial infarction. Case mix standardised 30 day mortality from acute myocardial infarction was lower in Swedish hospitals (8.4%) than in UK hospitals (9.7%), with less variation between hospitals (interquartile range 2.6% v 3.5%). In both countries, hospital level variation and 30 day mortality were inversely associated with provision of guideline recommended care. Compared with the highest quarter, hospitals in the lowest quarter for use of primary percutaneous coronary intervention had higher volume weighted 30 day mortality for ST elevation myocardial infarction (10.7% v 6.6% in Sweden; 12.7% v 5.8% in the UK). The adjusted odds ratio comparing the highest with the lowest quarters for hospitals' use of primary percutaneous coronary intervention was 0.70 (95% confidence interval 0.62 to 0.79) in Sweden and 0.68 (0.60 to 0.76) in the UK. Differences in risk between hospital quarters of treatment for non-ST elevation myocardial infarction and secondary prevention drugs for all discharged acute myocardial infarction patients were smaller than for reperfusion treatment in both countries. Between hospital variation in 30 day mortality for acute myocardial infarction was greater in the UK than in Sweden. This was associated with, and may be partly accounted for by, the higher practice variation in acute myocardial infarction guideline recommended treatment in the UK hospitals. High quality healthcare across all hospitals, especially in the UK, with better use of guideline recommended treatment, may not only reduce unacceptable practice variation but also deliver improved clinical outcomes for patients with acute myocardial infarction. Clinical trials registration Clinical trials NCT01359033. © Chung et al 2015.

Time and diffusion lesion size in major anterior circulation ischemic strokes.

PubMed

Hakimelahi, Reza; Vachha, Behroze A; Copen, William A; Papini, Giacomo D E; He, Julian; Higazi, Mahmoud M; Lev, Michael H; Schaefer, Pamela W; Yoo, Albert J; Schwamm, Lee H; González, R Gilberto

2014-10-01

Major anterior circulation ischemic strokes caused by occlusion of the distal internal carotid artery or proximal middle cerebral artery or both account for about one third of ischemic strokes with mostly poor outcomes. These strokes are treatable by intravenous tissue-type plasminogen activator and endovascular methods. However, dynamics of infarct growth in these strokes are poorly documented. The purpose was to help understand infarct growth dynamics by measuring acute infarct size with diffusion-weighted imaging (DWI) at known times after stroke onset in patients with documented internal carotid artery/middle cerebral artery occlusions. Retrospectively, we included 47 consecutive patients with documented internal carotid artery/middle cerebral artery occlusions who underwent DWI within 30 hours of stroke onset. Prospectively, 139 patients were identified using the same inclusion criteria. DWI lesion volumes were measured and correlated to time since stroke onset. Perfusion data were reviewed in those who underwent perfusion imaging. Acute infarct volumes ranged from 0.41 to 318.3 mL. Infarct size and time did not correlate (R2=0.001). The majority of patients had DWI lesions that were <25% the territory at risk (<70 mL) whether they were imaged <8 or >8 hours after stroke onset. DWI lesions corresponded to areas of greatly reduced perfusion. Poor correlation between infarct volume and time after stroke onset suggests that there are factors more powerful than time in determining infarct size within the first 30 hours. The observations suggest that highly variable cerebral perfusion via the collateral circulation may primarily determine infarct growth dynamics. If verified, clinical implications include the possibility of treating many patients outside traditional time windows. © 2014 American Heart Association, Inc.

Relationship between hippocampal subfield volumes and memory deficits in patients with thalamus infarction.

PubMed

Chen, Li; Luo, Tianyou; Lv, Fajin; Shi, Dandan; Qiu, Jiang; Li, Qi; Fang, Weidong; Peng, Juan; Li, Yongmei; Zhang, Zhiwei; Li, Yang

2016-09-01

Clinical studies have shown that thalamus infarction (TI) affects memory function. The thalamic nucleus is directly or indirectly connected to the hippocampal system in animal models. However, this connection has not been investigated using structural magnetic resonance imaging (MRI) in humans. From the pathological perspective, TI patients may serve as valid models for revealing the interaction between the thalamus and hippocampus in memory function. In this study, we aim to assess different hippocampal subfield volumes in TI patients and control subjects using MRI and test their associations with memory function. A total of 37 TI patients (TI group), 38 matched healthy control subjects (HC group), and 22 control patients with other stroke location (SC group) underwent 3.0-T MRI scans and clinical memory examinations. Hippocampal subfield volumes were measured and compared by using FreeSurfer software. We examined the correlation between hippocampal subfield volumes and memory scores. Smaller ipsilesional presubiculum and subiculum volumes were observed, and former was related to graphics recall in both left and right TI patients. The left subiculum volume was correlated with short-delayed recall in left TI patients. The right presubiculum volume was correlated with short- and long-delayed recall in right TI patients. TI was found to result in hippocampal abnormality and memory deficits, and its neural mechanisms might be related with and interaction between the thalamus and hippocampus.

Anisotropic Reinforcement of Acute Anteroapical Infarcts Improves Pump Function

PubMed Central

Fomovsky, Gregory M.; Clark, Samantha A.; Parker, Katherine M.; Ailawadi, Gorav; Holmes, Jeffrey W.

2012-01-01

Background We hypothesize that a therapy that improves LV pump function early after infarction should decrease the need for compensation through sympathetic activation and dilation, thereby reducing the risk of developing heart failure. The mechanical properties of healing myocardial infarcts are an important determinant of left ventricular (LV) function, yet improving function by altering infarct properties has proven unexpectedly difficult. Using a computational model, we recently predicted that stiffening a large anterior infarct anisotropically (in only one direction) would improve LV function, while isotropic stiffening, the focus of previous studies and therapies, would not. The goal of this study was to test the novel strategy of anisotropic infarct reinforcement. Methods and Results We tested the effects of anisotropic infarct reinforcement in 10 open-chest dogs with large anteroapical infarcts that depressed LV pump function. We measured regional mechanics, LV volumes, and cardiac output at a range of preloads at Baseline, 45 minutes after coronary ligation (Ischemia), and 30 minutes later, following surgical reinforcement in the longitudinal direction (Anisotropic). Ischemia shifted the end-systolic pressure-volume relationship (ESPVR) and cardiac output curves rightward, decreasing cardiac output at matched end-diastolic pressure (EDP) by 44%. Anisotropic reinforcement significantly improved systolic function without impairing diastolic function, recovering half the deficit in overall LV function. Conclusions We conclude that anisotropic reinforcement is a promising new approach to improving LV function following a large myocardial infarction. PMID:22665716

Left Ventricular Stroke Volume Quantification by Contrast Echocardiography – Comparison of Linear and Flow-Based Methods to Cardiac Magnetic Resonance

PubMed Central

Dele-Michael, Abiola O.; Fujikura, Kana; Devereux, Richard B; Islam, Fahmida; Hriljac, Ingrid; Wilson, Sean R.; Lin, Fay; Weinsaft, Jonathan W.

2014-01-01

Background Echocardiography (echo) quantified LV stroke volume (SV) is widely used to assess systolic performance after acute myocardial infarction (AMI). This study compared two common echo approaches – predicated on flow (Doppler) and linear chamber dimensions (Teichholz) – to volumetric SV and global infarct parameters quantified by cardiac magnetic resonance (CMR). Methods Multimodality imaging was performed as part of a post-AMI registry. For echo, SV was measured by Doppler and Teichholz methods. Cine-CMR was used for volumetric SV and LVEF quantification, and delayed-enhancement CMR for infarct size. Results 142 patients underwent same-day echo and CMR. On echo, mean SV by Teichholz (78±17ml) was slightly higher than Doppler (75±16ml; Δ=3±13ml, p=0.02). Compared to SV on CMR (78±18ml), mean difference by Teichholz (Δ=−0.2±14; p=0.89) was slightly smaller than Doppler (Δ−3±14; p=0.02) but limits of agreement were similar between CMR and echo methods (Teichholz: −28, 27 ml, Doppler: −31, 24ml). For Teichholz, differences with CMR SV were greatest among patients with anteroseptal or lateral wall hypokinesis (p<0.05). For Doppler, differences were associated with aortic valve abnormalities or root dilation (p=0.01). SV by both echo methods decreased stepwise in relation to global LV injury as assessed by CMR-quantified LVEF and infarct size (p<0.01). Conclusions Teichholz and Doppler calculated SV yield similar magnitude of agreement with CMR. Teichholz differences with CMR increase with septal or lateral wall contractile dysfunction, whereas Doppler yields increased offsets in patients with aortic remodeling. PMID:23488864

Exploratory analysis of glyburide as a novel therapy for preventing brain swelling.

PubMed

Sheth, Kevin N; Kimberly, W Taylor; Elm, Jordan J; Kent, Thomas A; Yoo, Albert J; Thomalla, Götz; Campbell, Bruce; Donnan, Geoffrey A; Davis, Stephen M; Albers, Gregory W; Jacobson, Sven; del Zoppo, Gregory; Simard, J Marc; Stern, Barney J; Mandava, Pitchaiah

2014-08-01

Malignant infarction is characterized by the formation of cerebral edema, and medical treatment is limited. Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. We previously reported feasibility of the GAMES-Pilot study, a two-center prospective, open label, phase IIa trial of 10 subjects at high risk for malignant infarction based on diffusion weighted imaging (DWI) threshold of 82 cm(3) treated with RP-1127 (glyburide for injection). In this secondary analysis, we tested the hypothesis that RP-1127 may be efficacious in preventing poor outcome when compared to controls. Controls suffering large hemispheric infarction were obtained from the EPITHET and MMI-MRI studies. We first screened subjects for controls with the same DWI threshold used for enrollment into GAMES-Pilot, 82 cm(3). Next, to address imbalances, we applied a weighted Euclidean matching. Ninety day mRS 0-4, rate of decompressive craniectomy, and mortality were the primary clinical outcomes of interest. The mean age of the GAMES cohort was 51 years and initial DWI volume was 102 ± 23 cm(3). After Euclidean matching, GAMES subjects showed similar NIHSS, higher DWI volume, younger age and had mRS 0-4-90% versus 50% in controls p = 0.049; with a similar trend in mRS 0-3 (40 vs. 25%; p = 0.43) and trend toward lower mortality (10 vs. 35%; p = 0.21). In this pilot study, RP-1127-treated subjects showed better clinical outcomes when compared to historical controls. An adequately powered and randomized phase II trial of patients at risk for malignant infarction is needed to evaluate the potential efficacy of RP-1127.

Biochemical and inflammatory biomarkers in ischemic stroke: translational study between humans and two experimental rat models

PubMed Central

2014-01-01

Background our objective was to examine the plasma levels of three biological markers involved in cerebral ischemia (IL-6, glutamate and TNF-alpha) in stroke patients and compare them with two different rat models of focal ischemia (embolic stroke model- ES and permanent middle cerebral artery occlusion ligation model-pMCAO) to evaluate which model is most similar to humans. Secondary objectives: 1) to analyze the relationship of these biological markers with the severity, volume and outcome of the brain infarction in humans and the two stroke models; and 2) to study whether the three biomarkers are also increased in response to damage in organs other than the central nervous system, both in humans and in rats. Methods Multi-center, prospective, case-control study including acute stroke patients (n = 58) and controls (n = 19) with acute non-neurological diseases Main variables: plasma biomarker levels on admission and at 72 h; stroke severity (NIHSS scale) and clinical severity (APACHE II scale); stroke volume; functional status at 3 months (modified Rankin Scale [mRS] and Barthel index [BI]). Experimental groups: ES (n = 10), pMCAO (n = 6) and controls (tissue stress by leg compression) (n = 6). Main variables: plasma biomarker levels at 3 and 72 h; volume of ischemic lesion (H&E) and cell death (TUNEL). Results in stroke patients, IL-6 correlated significantly with clinical severity (APACHE II scale), stroke severity (NIHSS scale), infarct volume (cm3) and clinical outcome (mRS) (r = 0.326, 0.497, 0.290 and 0.444 respectively; P < 0.05). Glutamate correlated with stroke severity, but not with outcome, and TNF-alpha levels with infarct volume. In animals, The ES model showed larger infarct volumes (median 58.6% vs. 29%, P < 0.001) and higher inflammatory biomarkers levels than pMCAO, except for serum glutamate levels which were higher in pMCAO. The ES showed correlations between the biomarkers and cell death (r = 0.928 for IL-6; P < 0.001; r = 0.765 for TNF-alpha, P < 0.1; r = 0.783 for Glutamate, P < 0.1) and infarct volume (r = 0.943 for IL-6, P < 0.0001) more similar to humans than pMCAO. IL-6, glutamate and TNF-α levels were not higher in cerebral ischemia than in controls. Conclusions Both models, ES and pMCAO, show differences that should be considered when conducting translational studies. IL-6, Glutamate and TNF-α are not specific for cerebral ischemia either in humans or in rats. PMID:25086655

Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice.

PubMed

Iismaa, Siiri E; Li, Ming; Kesteven, Scott; Wu, Jianxin; Chan, Andrea Y; Holman, Sara R; Calvert, John W; Haq, Ahtesham Ul; Nicks, Amy M; Naqvi, Nawazish; Husain, Ahsan; Feneley, Michael P; Graham, Robert M

2018-04-17

We have previously demonstrated that adult transgenic C57BL/6J mice with CM-restricted overexpression of the dominant negative W v mutant protein (dn-c-kit-Tg) respond to pressure overload with robust cardiomyocyte (CM) cell cycle entry. Here, we tested if outcomes after myocardial infarction (MI) due to coronary artery ligation are improved in this transgenic model. Compared to non-transgenic littermates (NTLs), adult male dn-c-kit-Tg mice displayed CM hypertrophy and concentric left ventricular (LV) hypertrophy in the absence of an increase in workload. Stroke volume and cardiac output were preserved and LV wall stress was markedly lower than that in NTLs, leading to a more energy-efficient heart. In response to MI, infarct size in adult (16-week old) dn-c-kit-Tg hearts was similar to that of NTL after 24 h but was half that in NTL hearts 12 weeks post-MI. Cumulative CM cell cycle entry was only modestly increased in dn-c-kit-Tg hearts. However, dn-c-kit-Tg mice were more resistant to infarct expansion, adverse LV remodelling and contractile dysfunction, and suffered no early death from LV rupture, relative to NTL mice. Thus, pre-existing cardiac hypertrophy lowers wall stress in dn-c-kit-Tg hearts, limits infarct expansion and prevents death from myocardial rupture.

[Diagnosis of myocardial infarction by cine MR imaging--a comparative study with thallium-201 myocardial SPECT].

PubMed

Shiozaki, H

1993-01-25

The usefulness of cine magnetic resonance (MR) imaging was evaluated in 41 patients with acute (4 cases), subacute (21 cases) and chronic (16 cases) myocardial infarctions on the basis of the findings of thallium-201 myocardial SPECT. The overall rate of diagnostic accordance between cine MR imaging and SPECT was 85.0% (408/480). It was highest at the middle of the left ventricle (89.0%, 146/164) and lowest at the base (82.7%, 129/156). Measurement of wall thickness using the images printed on films was possible in 87.1% of segments (418/480). There was a significant difference in end-diastolic wall thickness and %-thickening between the infarcted and non-infarcted sites except for the base of the left ventricle. However, diastolic wall thinning was not remarkable in acute cases of less than one week after onset. In these cases %-thickening may be useful. Partial volume averaging on MR imaging and the inaccuracy of SPECT findings at the base also made meaningful comparison difficult. The most important diagnostic findings of myocardial infarction on cine MR imaging were end-diastolic wall thinning and abnormal motion such as akinesis and dyskinesis. It is concluded that cine MR imaging is a useful noninvasive examination method for evaluating the status of cardiac function in myocardial infarction.

Automated cerebral infarct volume measurement in follow-up noncontrast CT scans of patients with acute ischemic stroke.

PubMed

Boers, A M; Marquering, H A; Jochem, J J; Besselink, N J; Berkhemer, O A; van der Lugt, A; Beenen, L F; Majoie, C B

2013-08-01

Cerebral infarct volume as observed in follow-up CT is an important radiologic outcome measure of the effectiveness of treatment of patients with acute ischemic stroke. However, manual measurement of CIV is time-consuming and operator-dependent. The purpose of this study was to develop and evaluate a robust automated measurement of the CIV. The CIV in early follow-up CT images of 34 consecutive patients with acute ischemic stroke was segmented with an automated intensity-based region-growing algorithm, which includes partial volume effect correction near the skull, midline determination, and ventricle and hemorrhage exclusion. Two observers manually delineated the CIV. Interobserver variability of the manual assessments and the accuracy of the automated method were evaluated by using the Pearson correlation, Bland-Altman analysis, and Dice coefficients. The accuracy was defined as the correlation with the manual assessment as a reference standard. The Pearson correlation for the automated method compared with the reference standard was similar to the manual correlation (R = 0.98). The accuracy of the automated method was excellent with a mean difference of 0.5 mL with limits of agreement of -38.0-39.1 mL, which were more consistent than the interobserver variability of the 2 observers (-40.9-44.1 mL). However, the Dice coefficients were higher for the manual delineation. The automated method showed a strong correlation and accuracy with the manual reference measurement. This approach has the potential to become the standard in assessing the infarct volume as a secondary outcome measure for evaluating the effectiveness of treatment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smeets, Albert J., E-mail: radiol@eztilburg.nl; Nijenhuis, Robbert J.; Rooij, Willem Jan van

Uterine artery embolization (UAE) in patients with a large fibroid burden is controversial. Anecdotal reports describe serious complications and limited clinical results. We report the long-term clinical and magnetic resonance (MR) results in a large series of women with a dominant fibroid of >10 cm and/or an uterine volume of >700 cm{sup 3}. Seventy-one consecutive patients (mean age, 42.5 years; median, 40 years; range, 25-52 years) with a large fibroid burden were treated by UAE between August 2000 and April 2005. Volume reduction and infarction rate of dominant fibroid and uterus were assessed by comparing the baseline and latest follow-upmore » MRIs. Patients were clinically followed at various time intervals after UAE with standardized questionnaires. There were no serious complications of UAE. During a mean follow-up of 48 months (median, 59 months; range, 6-106 months), 10 of 71 patients (14%) had a hysterectomy. Mean volume reduction of the fibroid and uterus was 44 and 43%. Mean infarction rate of the fibroid and overall fibroid infarction rate was 86 and 87%. In the vast majority of patients there was a substantial improvement of symptoms. Clinical results were similar in patients with a dominant fibroid >10 cm and in patients with large uterine volumes by diffuse fibroid disease. In conclusion, our results indicate that the risk of serious complications after UAE in patients with a large fibroid burden is not increased. Moreover, clinical long-term results are as good as in other patients who are treated with UAE. Therefore, a large fibroid burden should not be considered a contraindication for UAE.« less

Three Variations in Rabbit Angiographic Stroke Models

PubMed Central

Culp, William C.; Woods, Sean D.; Brown, Aliza T.; Lowery, John D.; Hennings, Leah J.; Skinner, Robert D.; Borrelli, Michael J.; Roberson, Paula K.

2012-01-01

Purpose To develop angiographic models of embolic stroke in the rabbit using pre-formed clot or microspheres to model clinical situations ranging from transient ischemic events to severe ischemic stroke. Materials and Methods New Zealand White rabbits (N=151) received angiographic access to the internal carotid artery (ICA) from a femoral approach. Variations of emboli type and quantity of emboli were tested by injection into the ICA. These included fresh clots (1.0-mm length, 3–6 h), larger aged clots (4.0-mm length, 3 days), and 2 or 3 insoluble microspheres (700–900 μm). Neurological assessment scores (NAS) were based on motor, sensory, balance, and reflex measures. Rabbits were euthanized at 4, 7, or 24 hours after embolization, and infarct volume was measured as a percent of total brain volume using 2,3,5-triphenyltetrazolium chloride (TTC). Results Infarct volume percent at 24 hours after stroke was lower for rabbits embolized with fresh clot (0.45% ± 0.14%), compared with aged clot (3.52% ± 1.31%) and insoluble microspheres (3.39% ± 1.04%). Overall NAS (including posterior vessel occlusions) were positively correlated to infarct volume percent measurements in the fresh clot (r=0.50), aged clot (r=0.65) and microsphere (r=0.62) models (p<0.001). Conclusion The three basic angiographic stroke models may be similar to human transient ischemic attacks (TIA) (fresh clot), major strokes that can be thrombolysed (aged clot), or major strokes with insoluble emboli such as atheromata (microspheres). Model selection can be tailored to specific research needs. PMID:23142182

Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy.

PubMed

Austein, Friederike; Riedel, Christian; Kerby, Tina; Meyne, Johannes; Binder, Andreas; Lindner, Thomas; Huhndorf, Monika; Wodarg, Fritz; Jansen, Olav

2016-09-01

Computed tomographic perfusion represents an interesting physiological imaging modality to select patients for reperfusion therapy in acute ischemic stroke. The purpose of our study was to determine the accuracy of different commercial perfusion CT software packages (Philips (A), Siemens (B), and RAPID (C)) to predict the final infarct volume (FIV) after mechanical thrombectomy. Single-institutional computed tomographic perfusion data from 147 mechanically recanalized acute ischemic stroke patients were postprocessed. Ischemic core and FIV were compared about thrombolysis in cerebral infarction (TICI) score and time interval to reperfusion. FIV was measured at follow-up imaging between days 1 and 8 after stroke. In 118 successfully recanalized patients (TICI 2b/3), a moderately to strongly positive correlation was observed between ischemic core and FIV. The highest accuracy and best correlation are shown in early and fully recanalized patients (Pearson r for A=0.42, B=0.64, and C=0.83; P<0.001). Bland-Altman plots and boxplots demonstrate smaller ranges in package C than in A and B. Significant differences were found between the packages about over- and underestimation of the ischemic core. Package A, compared with B and C, estimated more than twice as many patients with a malignant stroke profile (P<0.001). Package C best predicted hypoperfusion volume in nonsuccessfully recanalized patients. Our study demonstrates best accuracy and approximation between the results of a fully automated software (RAPID) and FIV, especially in early and fully recanalized patients. Furthermore, this software package overestimated the FIV to a significantly lower degree and estimated a malignant mismatch profile less often than other software. © 2016 American Heart Association, Inc.

Phosphorylation enhances recombinant HSP27 neuroprotection against focal cerebral ischemia in mice.

PubMed

Shimada, Y; Tanaka, R; Shimura, H; Yamashiro, K; Urabe, T; Hattori, N

2014-10-10

Heat shock protein 27 (HSP27) exerts cytoprotection against many cellular insults including cerebral ischemia. We previously indicated that intravenous injection of HSP27 purified from human lymphocytes (hHSP27) significantly reduced infarct volume following cerebral ischemia-reperfusion injury, while recombinant HSP27 (rHSP27) was less effective. Phosphorylation is important for HSP27 function, and hHSP27 was more highly phosphorylated than rHSP27. We hypothesized that MAPKAP kinase 2 in vitro-phosphorylated rHSP27 (prHSP27) might increase its brain protection. Mice underwent transient 1-h middle cerebral artery occlusion (MCAO), and then received tail-vein injections of one of the following 1h after reperfusion: hHSP27 as positive control, rHSP27, prHSP27, or bovine serum albumin (BSA) as control. We measured infarct volume, neurological deficits, neurological severity, physiological parameters, cell-death, oxidative stress, and inflammatory response. Compared with BSA controls (30.7±3.1mm(3), n=5), infarct volume was reduced by 67% in the hHSP27 positive-control group (10.1±4.6mm(3), P<0.001, n=5), 17% following rHSP27 (25.4±3.6mm(3), P<0.05, n=5), and 46% following prHSP27 (16.5±4.0mm(3), P<0.001, n=9). Compared to the rHSP27 and BSA-treated groups, prHSP27 also reduced functional deficits, and significantly suppressed apoptosis, oxidative stress, and inflammatory responses. Here, we showed the superior neuroprotective effects of phosphorylated HSP27 by administering prHSP27. prHSP27 may be a useful therapeutic agent to protect against acute cerebral ischemic stroke. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Comparison of polyvinyl alcohol and tris-acryl gelatin microsphere materials in embolization for symptomatic leiomyomas: a systematic review.

PubMed

Jiang, Wenxiao; Shen, Zhaojun; Luo, Hui; Hu, Xiaoli; Zhu, Xueqiong

2016-12-01

Use systematic reviews and meta-analyses to assess the effect of polyvinyl alcohol and tris-acryl gelatin microsphere materials in leiomyoma embolization for symptomatic leiomyomas. We included randomised controlled studies published before January 2015 comparing polyvinyl alcohol and tris-acryl gelatin microsphere materials in uterine leiomyoma embolization for women with symptomatic leiomyomas. The main outcome measures included change of overall quality of life, change of overall symptom severity, changes of uterine and leiomyoma volumes, leiomyoma infarction rate, treatment failure and complications. A total of six randomized controlled studies from 335 studies accounting for 351 women with leiomyomas were identified in this meta-analysis. Compared to polyvinyl alcohol, tris-acryl gelatin microsphere showed a significant benefit in improving the overall quality of life and in reducing uterine volume at three and six months, in reducing overall symptom severity at 6 and 12 months, and furthermore in reducing treatment failure. In addition, tris-acryl gelatin microsphere could significantly reduce leiomyoma volume and decrease <90% complete leiomyoma infarction rate at three months. There were no differences in pain severity, other post-procedural symptoms or medication use in the two groups. A better effect of tris-acryl gelatin microsphere in leiomyoma embolization for patients with symptomatic leiomyoma.

Functional CT assessment of extravascular contrast distribution volume and myocardial perfusion in acute myocardial infarction.

PubMed

So, Aaron; Wisenberg, Gerald; Teefy, Patrick; Yadegari, Andrew; Bagur, Rodrigo; Hadway, Jennifer; Morrison, Laura; MacDonald, Anna; Gaskin, Dave; Butler, John; Biernaski, Heather; Skanes, Stephanie; Park, Stella DohYeoun; Islam, Ali; Hsieh, Jiang; Lee, Ting-Yim

2018-04-26

In a pig model of acute myocardial infarction (AMI), we validated a functional computed tomography (CT) technique for concomitant assessment of myocardial edema and ischemia through extravscualar contrast distribution volume (ECDV) and myocardial perfusion (MP) measurements from a single dynamic imaging session using a single contrast bolus injection. In seven pigs, balloon catheter was used to occlude the distal left anterior descending artery for one hour followed by reperfusion. CT and cardiac magnetic resonance (CMR) imaging studies were acquired on 3 days and 12 ± 3 day post ischemic insult. In each CT study, 0.7 ml/kg of iodinated contrast was intravenously injected at 3-4 ml/s before dynamic contrast-enhanced (DCE) cardiac images were acquired with breath-hold using a 64-row CT scanner. DCE cardiac images were analyzed with a model-based deconvolution to generate ECDV and MP maps. ECDV as an imaging marker of edema was validated against CMR T2 weighted imaging in normal and infarcted myocardium delineated from ex-vivo histological staining. ECDV in infarcted myocardium was significantly higher (p < 0.05) than that in normal myocardium on both days post AMI and was in agreement with the findings of CMR T2 weighted imaging. MP was significantly lower (p < 0.05) in the infarcted region compared to normal on both days post AMI. This imaging technique can rapidly and simultaneously assess myocardial edema and ischemia through ECDV and MP measurements, and may be useful for delineation of salvageable tissue within at-risk myocardium to guide reperfusion therapy. Copyright © 2017. Published by Elsevier B.V.

Comparison of usefulness of N-terminal pro-brain natriuretic peptide as an independent predictor of cardiac function among admission cardiac serum biomarkers in patients with anterior wall versus nonanterior wall ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PubMed

Haeck, Joost D E; Verouden, Niels J W; Kuijt, Wichert J; Koch, Karel T; Van Straalen, Jan P; Fischer, Johan; Groenink, Maarten; Bilodeau, Luc; Tijssen, Jan G P; Krucoff, Mitchell W; De Winter, Robbert J

2010-04-15

The purpose of the present study was to determine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), among other serum biomarkers, on cardiac magnetic resonance (CMR) imaging parameters of cardiac function and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We measured NT-pro-BNP, cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and creatinine on the patients' arrival at the catheterization laboratory in 206 patients with ST-segment elevation myocardial infarction. The NT-pro-BNP levels were divided into quartiles and correlated with left ventricular function and infarct size measured by CMR imaging at 4 to 6 months. Compared to the lower quartiles, patients with nonanterior wall myocardial infarction in the highest quartile of NT-pro-BNP (> or = 260 pg/ml) more often had a greater left ventricular end-systolic volume (68 vs 39 ml/m(2), p <0.001), a lower left ventricular ejection fraction (42% vs 54%, p <0.001), a larger infarct size (9 vs 4 g/m(2), p = 0.002), and a larger number of transmural segments (11% of segments vs 3% of segments, p <0.001). Multivariate analysis revealed that a NT-pro-BNP level of > or = 260 pg/ml was the strongest independent predictor of left ventricular ejection fraction in patients with nonanterior wall myocardial infarction compared to the other serum biomarkers (beta = -5.8; p = 0.019). In conclusion, in patients with nonanterior wall myocardial infarction undergoing primary percutaneous coronary intervention, an admission NT-pro-BNP level of > or = 260 pg/ml was a strong, independent predictor of left ventricular function assessed by CMR imaging at follow-up. Our findings suggest that NT-pro-BNP, a widely available biomarker, might be helpful in the early risk stratification of patients with nonanterior wall myocardial infarction. Copyright 2010 Elsevier Inc. All rights reserved.

Clinical evaluation of post-operative cerebral infarction in traumatic epidural haematoma.

PubMed

Zhang, Suojun; Wang, Sheng; Wan, Xueyan; Liu, Shengwen; Shu, Kai; Lei, Ting

2017-01-01

Patients with traumatic epidural haematoma, undergoing the prompt and correct treatment, usually have favourable outcomes. However, secondary cerebral infarction may be life-threatening condition, as it is difficult to be identified before neurological impairment occurs. To evaluate the clinical data of patients with traumatic EDH and assess potential risk factors for post-operative cerebral infarction. The clinical data of patients with traumatic EDH were collected and analysed retrospectively. The univariate analysis revealed 10 potential risk factors (the haematoma location, volume, the largest thickness and mid-line shift, basal cisterns compression, traumatic subarachnoid haemorrhage, pupil dilatation, pre-operative Glasgow Coma Scale score, ∆GCS and intraoperative brain pressure) for cerebral infarction with statistically significant difference. Of these factors, haematoma volume and basal cistern compression turned out to be the most significant risk factors through final multivariate logistic regression analysis. The findings of this study can provide predictive factors for development of cerebral infarction and information for clinical decision-making and future studies.

Dermal Filler Injection: A Novel Approach for Limiting Infarct Expansion

PubMed Central

Ryan, Liam P.; Matsuzaki, Kanji; Noma, Mio; Jackson, Benjamin M.; Eperjesi, Thomas J.; Plappert, Theodore J.; St. John-Sutton, Martin G.; Gorman, Joseph H.; Gorman, Robert C.

2011-01-01

Background Early infarct expansion after coronary occlusion compromises contractile function in perfused myocardial regions and promotes adverse long-term left ventricular (LV) remodeling. We hypothesized that injection of a tissue-expanding dermal filler material into a myocardial infarction (MI) would attenuate infarct expansion and limit LV remodeling. Methods Fifteen sheep were subjected to an anteroapical MI involving approximately 20% of the LV followed by the injection of 1.3 mL of a calcium hydroxyapatite–based dermal filler into the infarct. Real-time three-dimensional echocardiography was performed at baseline, 30 minutes after MI, and 15 minutes after injection to assess infarct expansion. Sixteen additional sheep were subjected to the same infarction and followed echocardiographically and hemodynamically for 4 weeks after MI to assess chronic remodeling. Eight animals had injection with dermal filler as described above immediately after MI, and 8 animals were injected with an equal amount of saline solution. Results All animals exhibited infarct expansion soon after coronary occlusion. The regional ejection fraction of the apex became negative after infarction, consistent with systolic dyskinesia. Injection of the dermal filler converted the apical wall motion from dyskinetic to akinetic and resulted immediately in significant decreases in global, regional, and segmental LV volumes. Chronically, relative to saline control, dermal filler injection significantly reduced LV end-systolic volume (62.2 ± 3.6 mL versus 44.5 ± 3.9 mL; p < 0.05) and improved global ejection fraction (0.295 ± 0.016 versus 0.373 ± 0.017; p < 0.05) at 4 weeks after infarction. Conclusions Injection of an acellular dermal filler into an MI immediately after coronary occlusion reduces early infarct expansion and limits chronic LV remodeling. PMID:19101288

Serum S100B is a useful surrogate marker for long-term outcomes in photochemically-induced thrombotic stroke rat models.

PubMed

Tanaka, Yu; Koizumi, Chie; Marumo, Toshiyuki; Omura, Tomohiro; Yoshida, Shigeru

2007-08-02

In recent years, serum S100B has been used as a secondary endpoint in some clinical trials, in which serum S100B has successfully indicated the benefits or harm done by the tested agents. Compared to clinical stroke studies, few experimental stroke studies report using serum S100B as a surrogate marker for estimating the long-term effects of neuroprotectants. This study sought to observe serum S100B kinetics in PIT stroke models and to clarify the association between serum S100B and both final infarct volumes and long-term neurological outcomes. Furthermore, to demonstrate that early elevations in serum S100B reflect successful neuroprotective treatment, a pharmacological study was performed with a non-competitive NMDA glutamate receptor antagonist, MK-801. Serum S100B levels were significantly elevated after PIT stroke, reaching peak values 48 h after the onset and declining thereafter. Single measurements of serum S100B as early as 48 h after PIT stroke correlated significantly with final infarct volumes and long-term neurological outcomes. Elevated serum S100B was significantly attenuated by MK-801, correlating significantly with long-term beneficial effects of MK-801 on infarct volumes and neurological outcomes. Our results showed that single measurements of serum S100B 48 h after PIT stroke would serve as an early and simple surrogate marker for long-term evaluation of histological and neurological outcomes in PIT stroke rat models.

Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults.

PubMed

Schaapsmeerders, Pauline; van Uden, Inge W M; Tuladhar, Anil M; Maaijwee, Noortje A M; van Dijk, Ewoud J; Rutten-Jacobs, Loes C A; Arntz, Renate M; Schoonderwaldt, Hennie C; Dorresteijn, Lucille D A; de Leeuw, Frank-Erik; Kessels, Roy P C

2015-07-01

Memory impairment after stroke in young adults is poorly understood. In elderly stroke survivors memory impairments and the concomitant loss of hippocampal volume are usually explained by coexisting neurodegenerative disease (e.g., amyloid pathology) in interaction with stroke. However, neurodegenerative disease, such as amyloid pathology, is generally absent at young age. Accumulating evidence suggests that infarction itself may cause secondary neurodegeneration in remote areas. Therefore, we investigated the relation between long-term memory performance and hippocampal volume in young patients with first-ever ischemic stroke. We studied all consecutive first-ever ischemic stroke patients, aged 18-50 years, admitted to our academic hospital center between 1980 and 2010. Episodic memory of 173 patients was assessed using the Rey Auditory Verbal Learning Test and the Rey Complex Figure and compared with 87 stroke-free controls. Hippocampal volume was determined using FSL-FIRST, with manual correction. On average 10 years after stroke, patients had smaller ipsilateral hippocampal volumes compared with controls after left-hemispheric stroke (5.4%) and right-hemispheric stroke (7.7%), with most apparent memory dysfunctioning after left-hemispheric stroke. A larger hemispheric stroke was associated with a smaller ipsilateral hippocampal volume (b=-0.003, P<0.0001). Longer follow-up duration was associated with smaller ipsilateral hippocampal volume after left-hemispheric stroke (b=-0.028 ml, P=0.002) and right-hemispheric stroke (b=-0.015 ml, P=0.03). Our results suggest that infarction is associated with remote injury to the hippocampus, which may lower or expedite the threshold for cognitive impairment or even dementia later in life. © 2015 Wiley Periodicals, Inc.

Relationship of ischemic times and left atrial volume and function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

PubMed

Ilic, Ivan; Stankovic, Ivan; Vidakovic, Radosav; Jovanovic, Vladimir; Vlahovic Stipac, Alja; Putnikovic, BiIjana; Neskovic, Aleksandar N

2015-04-01

Little is known about the impact of duration of ischemia on left atrial (LA) volumes and function during acute phase of myocardial infarction. We investigated the relationship of ischemic times, echocardiographic indices of diastolic function and LA volumes in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). A total of 433 consecutive STEMI patients underwent echocardiographic examination within 48 h of primary PCI, including the measurement of LA volumes and the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e'). Time intervals from onset of chest pain to hospital admission and reperfusion were collected and magnitude of Troponin I release was used to assess infarct size. Patients with LA volume index (LAVI) ≥28 ml/m(2) had longer total ischemic time (410 ± 347 vs. 303 ± 314 min, p = 0.007) and higher E/e' ratio (15 ± 5 vs. 10 ± 3, p < 0.001) than those with LAVI <28 ml/m(2), while the indices of LA function were similar between the study groups (p > 0.05, for all). Significant correlation was found between E/e' and LA volumes at all stages of LA filling and contraction (r = 0.363-0.434; p < 0.001, for all) while total ischemic time along with E/e' and restrictive filling pattern remained independent predictor of LA enlargement. Increased LA volume is associated with longer ischemic times and may be a sensitive marker of increased left ventricular filling pressures in STEMI patients treated with primary PCI.

Intravenously Delivered Mesenchymal Stem Cells: Systemic Anti-Inflammatory Effects Improve Left Ventricular Dysfunction in Acute Myocardial Infarction and Ischemic Cardiomyopathy.

PubMed

Luger, Dror; Lipinski, Michael J; Westman, Peter C; Glover, David K; Dimastromatteo, Julien; Frias, Juan C; Albelda, M Teresa; Sikora, Sergey; Kharazi, Alex; Vertelov, Grigory; Waksman, Ron; Epstein, Stephen E

2017-05-12

Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O 2 , were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×10 6 ) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×10 6 MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were randomized to tail-vein injection of 2×10 6 MSCs, with injection repeated at week 3 (n=16) versus PBS control (n=16). MSCs significantly increased LV ejection fraction and decreased LV end-systolic volume. Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities. © 2017 American Heart Association, Inc.

[Application of diffusion tensor imaging in judging infarction time of acute ischemic cerebral infarction].

PubMed

Dai, Zhenyu; Chen, Fei; Yao, Lizheng; Dong, Congsong; Liu, Yang; Shi, Haicun; Zhang, Zhiping; Yang, Naizhong; Zhang, Mingsheng; Dai, Yinggui

2015-08-18

To evaluate the clinical application value of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in judging infarction time phase of acute ischemic cerebral infarction. To retrospective analysis DTI images of 52 patients with unilateral acute ischemic cerebral infarction (hyper-acute, acute and sub-acute) from the Affiliated Yancheng Hospital of Southeast University Medical College, which diagnosed by clinic and magnetic resonance imaging. Set the regions of interest (ROIs) of infarction lesions, brain tissue close to infarction lesions and corresponding contra (contralateral normal brain tissue) on DTI parameters mapping of fractional anisotropy (FA), volume ratio anisotropy (VRA), average diffusion coefficient (DCavg) and exponential attenuation (Exat), record the parameters values of ROIs and calculate the relative parameters value of infarction lesion to contra. Meanwhile, reconstruct the DTT images based on the seed points (infarction lesion and contra). The study compared each parameter value of infarction lesions, brain tissue close to infarction lesions and corresponding contra, also analysed the differences of relative parameters values in different infarction time phases. The DTT images of acute ischemic cerebral infarction in each time phase could show the manifestation of fasciculi damaged. The DCavg value of cerebral infarction lesions was lower and the Exat value was higher than contra in each infarction time phase (P<0.05). The FA and VRA value of cerebral infarction lesions were reduced than contra only in acute and sub-acute infarction (P<0.05). The FA, VRA and Exat value of brain tissue close to infarction lesions were increased and DCavg value was decreased than contra in hyper-acute infarction (P<0.05). There were no statistic differences of FA, VRA, DCavg and Exat value of brain tissue close to infarction lesions in acute and sub-acute infarction. The relative FA and VRA value of infarction lesion to contra gradually decreased from hyper-acute to sub-acute cerebral infarction (P<0.05), but there were no difference of the relative VRA value between acute and sub-acute cerebral infarction. The relative DCavg value of infarction lesion to contra in hyper-acute infarction than that in acute and sub-acute infarction (P<0.05), however there was also no difference between acute and sub-acute infarction. ROC curve showed the best diagnosis cut off value of relative FA, VRA and DCavg of infarction lesions to contra were 0.852, 0.886 and 0.541 between hyper-acute and acute cerebral infarction, the best diagnosis cut off value of relative FA was 0.595 between acute and sub-acute cerebral infarction, respectively. The FA, VRA, DCavg and Exat value have specific change mode in acute ischemic cerebral infarction of different infarction time phases, which can be combine used in judging infarction time phase of acute ischemic cerebral infarction without clear onset time, thus to help selecting the reasonable treatment protocols.

Comparison of hospital variation in acute myocardial infarction care and outcome between Sweden and United Kingdom: population based cohort study using nationwide clinical registries

PubMed Central

Sundström, Johan; Gale, Chris P; James, Stefan; Deanfield, John; Wallentin, Lars; Timmis, Adam; Jernberg, Tomas; Hemingway, Harry

2015-01-01

Objective To assess the between hospital variation in use of guideline recommended treatments and clinical outcomes for acute myocardial infarction in Sweden and the United Kingdom. Design Population based longitudinal cohort study using nationwide clinical registries. Setting and participants Nationwide registry data comprising all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART/RIKS-HIA, n=87; 119 786 patients) and the UK (NICOR/MINAP, n=242; 391 077 patients), 2004-10. Main outcome measures Between hospital variation in 30 day mortality of patients admitted with acute myocardial infarction. Results Case mix standardised 30 day mortality from acute myocardial infarction was lower in Swedish hospitals (8.4%) than in UK hospitals (9.7%), with less variation between hospitals (interquartile range 2.6% v 3.5%). In both countries, hospital level variation and 30 day mortality were inversely associated with provision of guideline recommended care. Compared with the highest quarter, hospitals in the lowest quarter for use of primary percutaneous coronary intervention had higher volume weighted 30 day mortality for ST elevation myocardial infarction (10.7% v 6.6% in Sweden; 12.7% v 5.8% in the UK). The adjusted odds ratio comparing the highest with the lowest quarters for hospitals’ use of primary percutaneous coronary intervention was 0.70 (95% confidence interval 0.62 to 0.79) in Sweden and 0.68 (0.60 to 0.76) in the UK. Differences in risk between hospital quarters of treatment for non-ST elevation myocardial infarction and secondary prevention drugs for all discharged acute myocardial infarction patients were smaller than for reperfusion treatment in both countries. Conclusion Between hospital variation in 30 day mortality for acute myocardial infarction was greater in the UK than in Sweden. This was associated with, and may be partly accounted for by, the higher practice variation in acute myocardial infarction guideline recommended treatment in the UK hospitals. High quality healthcare across all hospitals, especially in the UK, with better use of guideline recommended treatment, may not only reduce unacceptable practice variation but also deliver improved clinical outcomes for patients with acute myocardial infarction. Clinical trials registration Clinical trials NCT01359033. PMID:26254445

[Comparison of Quantification of Myocardial Infarct Size by One Breath Hold Single Shot PSIR Sequence and Segmented FLASH-PSIR Sequence at 3. 0 Tesla MR].

PubMed

Cheng, Wei; Cai, Shu; Sun, Jia-yu; Xia, Chun-chao; Li, Zhen-lin; Chen, Yu-cheng; Zhong, Yao-zu

2015-05-01

To compare the two sequences [single shot true-FISP-PSIR (single shot-PSIR) and segmented-turbo-FLASH-PSIR (segmented-PSIR)] in the value of quantification for myocardial infarct size at 3. 0 tesla MRI. 38 patients with clinical confirmed myocardial infarction were served a comprehensive gadonilium cardiac MRI at 3. 0 tesla MRI system (Trio, Siemens). Myocardial delayed enhancement (MDE) were performed by single shot-PSIR and segmented-PSIR sequences separatedly in 12-20 min followed gadopentetate dimeglumine injection (0. 15 mmol/kg). The quality of MDE images were analysed by experienced physicians. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) between the two techniques were compared. Myocardial infarct size was quantified by a dedicated software automatically (Q-mass, Medis). All objectives were scanned on the 3. 0T MR successfully. No significant difference was found in SNR and CNR of the image quality between the two sequences (P>0. 05), as well as the total myocardial volume, between two sequences (P>0. 05). Furthermore, there were still no difference in the infarct size [single shot-PSIR (30. 87 ± 15. 72) mL, segmented-PSIR (29. 26±14. 07) ml], ratio [single shot-PSIR (22. 94%±10. 94%), segmented-PSIR (20. 75% ± 8. 78%)] between the two sequences (P>0. 05). However, the average aquisition time of single shot-PSIR (21. 4 s) was less than that of the latter (380 s). Single shot-PSIR is equal to segmented-PSIR in detecting the myocardial infarct size with less acquisition time, which is valuable in the clinic application and further research.

Intraoperative laser speckle contrast imaging improves the stability of rodent middle cerebral artery occlusion model

NASA Astrophysics Data System (ADS)

Yuan, Lu; Li, Yao; Li, Hangdao; Lu, Hongyang; Tong, Shanbao

2015-09-01

Rodent middle cerebral artery occlusion (MCAO) model is commonly used in stroke research. Creating a stable infarct volume has always been challenging for technicians due to the variances of animal anatomy and surgical operations. The depth of filament suture advancement strongly influences the infarct volume as well. We investigated the cerebral blood flow (CBF) changes in the affected cortex using laser speckle contrast imaging when advancing suture during MCAO surgery. The relative CBF drop area (CBF50, i.e., the percentage area with CBF less than 50% of the baseline) showed an increase from 20.9% to 69.1% when the insertion depth increased from 1.6 to 1.8 cm. Using the real-time CBF50 marker to guide suture insertion during the surgery, our animal experiments showed that intraoperative CBF-guided surgery could significantly improve the stability of MCAO with a more consistent infarct volume and less mortality.

Adipose-Derived Cell Construct Stabilizes Heart Function and Increases Microvascular Perfusion in an Established Infarct

PubMed Central

Nguyen, Quang T.; Touroo, Jeremy S.; Aird, Allison L.; Chang, Raymond C.; Ng, Chin K.; Hoying, James B.; Williams, Stuart K.

2013-01-01

We have previously shown that myocardial infarction (MI) immediately treated with an epicardial construct containing stromal vascular fraction (SVF) from adipose tissue preserved microvascular function and left ventricle contractile mechanisms. In order to evaluate a more clinically relevant condition, we investigated the cardiac recovery potential of an SVF construct implanted onto an established infarct. SVF cells were isolated from rat adipose tissue, plated on Vicryl, and cultured for 14 days. Fischer-344 rats were separated into MI groups: (a) 6-week MI (MI), (b) 6-week MI treated with an SVF construct at 2 weeks (MI SVF), (c) 6-week MI with Vicryl construct at 2 weeks (MI Vicryl), and (d) MI 2wk (time point of intervention). Emax, an indicator of systolic performance and contractile function, was lower in the MI and MI Vicryl versus MI SVF. Positron emission tomography imaging (18F-fluorodeoxyglucose) revealed a decreased percentage of relative infarct volume in the MI SVF versus MI and MI Vicryl. Total vessel count and percentage of perfusion assessed via immunohistochemistry were both increased in the infarct region of MI SVF versus MI and MI Vicryl. Overall cardiac function, percentage of relative infarct, and percentage of perfusion were similar between MI SVF and MI 2wk; however, total vessel count increased after SVF treatment. These data suggest that SVF treatment of an established infarct stabilizes the heart at the time point of intervention by preventing a worsening of cardiac performance and infarcted volume, and is associated with increased microvessel perfusion in the area of established infarct. PMID:24106337

Longitudinal left ventricular function is globally depressed within a week of STEMI.

PubMed

Pahlm, Ulrika; Seemann, Felicia; Engblom, Henrik; Gyllenhammar, Tom; Halvorsen, Sigrun; Hansen, Henrik Steen; Erlinge, David; Atar, Dan; Heiberg, Einar; Arheden, Håkan; Carlsson, Marcus

2018-04-27

Sixty percent of stroke volume (SV) is generated by atrioventricular plane displacement (AVPD) in a healthy left ventricle (LV). The aims were to determine the effect of ST-elevation myocardial infarction (STEMI) on AVPD and contribution of AVPD to SV and to study the relationship between AVPD and infarct size (IS) and location. Patients from CHILL-MI and MITOCARE studies with cardiovascular magnetic resonance within a week of STEMI (n = 177, 59 ± 11 years) and healthy controls (n = 20, 62 ± 11 years) were included. Left ventricular volumes were quantified in short-axis images. AVPD was measured in six locations in long-axis images. Longitudinal contribution to SV was calculated as AVPD multiplied by the short-axis epicardial area. Patients (IS 17 ± 10% of LV) had decreased ejection fraction (48 ± 8%) compared to controls (60 ± 5%, P<0·001). Global AVPD was decreased in patients (11 ± 2 mm versus 15 ± 2 mm in controls, P<0·001) and this held true for both infarcted and remote segments. AVPD contribution to SV was lower in patients (58 ± 9%) than in controls (64 ± 8%) (P<0·001). There was a weak negative correlation between IS and AVPD (r 2 =0·06) but no differences in global AVPD linked to infarct location. Decrease in global and regional AVPD occur even in remote myocardium within 1 week of STEMI. Global AVPD decrease is independent of MI location, and MI size has only minor effect. Longitudinal pumping is slightly lower compared to controls but remains to be the main component to SV even after STEMI. These results highlight the difficulty in determining infarct location and size from longitudinal measures of LV function. © 2018 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd. on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Ablation of the sphenopalatine ganglion does not attenuate the infarct reducing effect of vagus nerve stimulation

PubMed Central

Ay, Ilknur; Ay, Hakan

2013-01-01

Electrical stimulation of the cervical vagus nerve reduces infarct size by approximately 50% after cerebral ischemia in rats. The mechanism of ischemic protection by vagus nerve stimulation (VNS) is not known. In this study, we investigated whether the infarct reducing effect of VNS was mediated by activation of the parasympathetic vasodilator fibers that originate from the sphenopalatine ganglion (SPG) and innervate the anterior cerebral circulation. We examined the effects of electrical stimulation of the cervical vagus nerve in two groups of rats: one with and one without SPG ablation. Electrical stimulation was initiated 30 min after induction of ischemia, and lasted for 1h. Measurement of infarct size 24h later revealed that the volume of ischemic damage was smaller in those animals that received VNS treatment (41.32 ± 2.07% vs. 24.19 ± 2.62% of the contralateral hemispheric volume, n=6 in both; p<0.05). SPG ablation did not abolish this effect; the reduction in infarct volume following VNS was 58% in SPG-damaged animals, 41% in SPG-intact animals (p>0.05). In both SPG-intact and SPG-damaged animals VNS treatment resulted in better motor outcome (p<0.05 vs. corresponding controls for both). Our findings show that VNS can protect the brain against acute ischemic injury, and that this effect is not mediated by SPG projections. PMID:23273773

Value of Quantitative Collateral Scoring on CT Angiography in Patients with Acute Ischemic Stroke.

PubMed

Boers, A M M; Sales Barros, R; Jansen, I G H; Berkhemer, O A; Beenen, L F M; Menon, B K; Dippel, D W J; van der Lugt, A; van Zwam, W H; Roos, Y B W E M; van Oostenbrugge, R J; Slump, C H; Majoie, C B L M; Marquering, H A

2018-06-01

Many studies have emphasized the relevance of collateral flow in patients presenting with acute ischemic stroke. Our aim was to evaluate the relationship of the quantitative collateral score on baseline CTA with the outcome of patients with acute ischemic stroke and test whether the timing of the CTA acquisition influences this relationship. From the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) data base, all baseline thin-slice CTA images of patients with acute ischemic stroke with intracranial large-vessel occlusion were retrospectively collected. The quantitative collateral score was calculated as the ratio of the vascular appearance of both hemispheres and was compared with the visual collateral score. Primary outcomes were 90-day mRS score and follow-up infarct volume. The relation with outcome and the association with treatment effect were estimated. The influence of the CTA acquisition phase on the relation of collateral scores with outcome was determined. A total of 442 patients were included. The quantitative collateral score strongly correlated with the visual collateral score (ρ = 0.75) and was an independent predictor of mRS (adjusted odds ratio = 0.81; 95% CI, .77-.86) and follow-up infarct volume (exponent β = 0.88; P < .001) per 10% increase. The quantitative collateral score showed areas under the curve of 0.71 and 0.69 for predicting functional independence (mRS 0-2) and follow-up infarct volume of >90 mL, respectively. We found significant interaction of the quantitative collateral score with the endovascular therapy effect in unadjusted analysis on the full ordinal mRS scale ( P = .048) and on functional independence ( P = .049). Modification of the quantitative collateral score by acquisition phase on outcome was significant (mRS: P = .004; follow-up infarct volume: P < .001) in adjusted analysis. Automated quantitative collateral scoring in patients with acute ischemic stroke is a reliable and user-independent measure of the collateral capacity on baseline CTA and has the potential to augment the triage of patients with acute stroke for endovascular therapy. © 2018 by American Journal of Neuroradiology.

Optical metrics of the extracellular matrix predict compositional and mechanical changes after myocardial infarction

NASA Astrophysics Data System (ADS)

Quinn, Kyle P.; Sullivan, Kelly E.; Liu, Zhiyi; Ballard, Zachary; Siokatas, Christos; Georgakoudi, Irene; Black, Lauren D.

2016-11-01

Understanding the organization and mechanical function of the extracellular matrix (ECM) is critical for the development of therapeutic strategies that regulate wound healing following disease or injury. However, these relationships are challenging to elucidate during remodeling following myocardial infarction (MI) due to rapid changes in cellularity and an inability to characterize both ECM microstructure and function non-destructively. In this study, we overcome those challenges through whole organ decellularization and non-linear optical microscopy to directly relate the microstructure and mechanical properties of myocardial ECM. We non-destructively quantify collagen organization, content, and cross-linking within decellularized healthy and infarcted myocardium using second harmonic generation (SHG) and two photon excited autofluorescence. Tensile mechanical testing and compositional analysis reveal that the cumulative SHG intensity within each image volume and the average collagen autofluorescence are significantly correlated with collagen content and elastic modulus of the ECM, respectively. Compared to healthy ECM, infarcted tissues demonstrate a significant increase in collagen content and fiber alignment, and a decrease in cross-linking and elastic modulus. These findings indicate that cross-linking plays a key role in stiffness at the collagen fiber level following infarction, and highlight how this non-destructive approach to assessing remodeling can be used to understand ECM structure-function relationships.

Hospital volume of throughput and periprocedural and medium‐term adverse events after percutaneous coronary intervention: retrospective cohort study of all 17 417 procedures undertaken in Scotland, 1997–2003

PubMed Central

Burton, K R; Slack, R; Oldroyd, K G; Pell, A C H; Flapan, A D; Starkey, I R; Eteiba, H; Jennings, K P; Northcote, R J; Hillis, W Stewart; Pell, J P

2006-01-01

Objective To determine whether percutaneous coronary intervention (PCI) hospital volume of throughput is associated with periprocedural and medium‐term events, and whether any associations are independent of differences in case mix. Design Retrospective cohort study of all PCIs undertaken in Scottish National Health Service hospitals over a six‐year period. Methods All PCIs in Scotland during 1997–2003 were examined. Linkage to administrative databases identified events over two years' follow up. The risk of events by hospital volume at 30 days and two years was compared by using logistic regression and Cox proportional hazards models. Results Of the 17 417 PCIs, 4900 (28%) were in low‐volume hospitals and 3242 (19%) in high‐volume hospitals. After adjustment for case mix, there were no significant differences in risk of death or myocardial infarction. Patients treated in high‐volume hospitals were less likely to require emergency surgery (adjusted odds ratio 0.18, 95% confidence interval (CI) 0.07 to 0.54, p  =  0.002). Over two years, patients in high‐volume hospitals were less likely to undergo surgery (adjusted hazard ratio 0.52, 95% CI 0.35 to 0.75, p  =  0.001), but this was offset by an increased likelihood of further PCI. There was no net difference in coronary revascularisation or in overall events. Conclusion Death and myocardial infarction were infrequent complications of PCI and did not differ significantly by volume. Emergency surgery was less common in high‐volume hospitals. Over two years, patients treated in high‐volume centres were as likely to undergo some form of revascularisation but less likely to undergo surgery. PMID:16709693

Hospital volume of throughput and periprocedural and medium-term adverse events after percutaneous coronary intervention: retrospective cohort study of all 17,417 procedures undertaken in Scotland, 1997-2003.

PubMed

Burton, K R; Slack, R; Oldroyd, K G; Pell, A C H; Flapan, A D; Starkey, I R; Eteiba, H; Jennings, K P; Northcote, R J; Hillis, W Stewart; Pell, J P

2006-11-01

To determine whether percutaneous coronary intervention (PCI) hospital volume of throughput is associated with periprocedural and medium-term events, and whether any associations are independent of differences in case mix. Retrospective cohort study of all PCIs undertaken in Scottish National Health Service hospitals over a six-year period. All PCIs in Scotland during 1997-2003 were examined. Linkage to administrative databases identified events over two years' follow up. The risk of events by hospital volume at 30 days and two years was compared by using logistic regression and Cox proportional hazards models. Of the 17,417 PCIs, 4900 (28%) were in low-volume hospitals and 3242 (19%) in high-volume hospitals. After adjustment for case mix, there were no significant differences in risk of death or myocardial infarction. Patients treated in high-volume hospitals were less likely to require emergency surgery (adjusted odds ratio 0.18, 95% confidence interval (CI) 0.07 to 0.54, p = 0.002). Over two years, patients in high-volume hospitals were less likely to undergo surgery (adjusted hazard ratio 0.52, 95% CI 0.35 to 0.75, p = 0.001), but this was offset by an increased likelihood of further PCI. There was no net difference in coronary revascularisation or in overall events. Death and myocardial infarction were infrequent complications of PCI and did not differ significantly by volume. Emergency surgery was less common in high-volume hospitals. Over two years, patients treated in high-volume centres were as likely to undergo some form of revascularisation but less likely to undergo surgery.

6-Mercaptopurine exerts an immunomodulatory and neuroprotective effect on permanent focal cerebral occlusion in rats.

PubMed

Chang, Chih-Zen; Kwan, Aij-Lie; Howng, Shen-Long

2010-08-01

A bursting cascade of inflammation imposes progressive neurological deterioration after experimental stroke has been demonstrated. In our study, 6-mercaptopurine (6-mp) has been successful in alleviating cerebral infarct in a rodent permanent middle cerebral artery occlusion (pMCAO) model. The present study was aimed to examine the effect of 6-mp on cytokine levels in experimental stroke. The rodent pMCAO model was employed. A dose of 2 mg/kg 6-mp or vehicle (0.1 mol/L PBS) was administered intraperitoneally 30 min after the induction of pMCAO. Neurological score, serum, and cerebrospinal fluid (CSF) cytokines such as IL-1beta, IL-6, and TNF-alpha and infarct volume were determined 48 h after pMCAO. Cerebral infarction volume was significantly decreased in animals treated with 6-mp (74.3%, p < 0.01), and the ratio of tissue edema was also decreased in 6-mp-treated groups (71%). Animals receiving 6-mp thus showed a significant decrease in IL-1 and TNF-alpha (18/43% and 48/64% in CSF/serum, respectively) when compared with the pMCAO groups (p < 0.01). This study demonstrates that 6-mp interposes the production of IL-1 and TNF-alpha in CSF and serum, attenuates ischemic brain injury, and thus alleviates neurological deficits in the pMCAO animals. These findings also offer first evidence that 6-mp may attenuate TNF-alpha-related neuron apoptosis and also support the notion that 6-mp and other anti-inflammatory agents could potentially have therapeutic uses in cases of cerebral infarct.

Zinc translocation accelerates infarction after mild transient focal ischemia.

PubMed

Lee, J-M; Zipfel, G J; Park, K H; He, Y Y; Hsu, C Y; Choi, D W

2002-01-01

Excess release of chelatable zinc (Zn(2+)) from central synaptic vesicles may contribute to the pathogenesis of selective neuronal cell death following transient forebrain ischemia, but a role in neurodegeneration after focal ischemia has not been defined. Adult male Long-Evans rats subjected to middle cerebral artery occlusion (MCAO) for 30 min followed by reperfusion developed delayed cerebral infarction reaching completion 3 days after the insult. One day after the insult, many degenerating cerebral neurons exhibited increased intracellular Zn(2+), and some labeled with the antibody against activated caspase-3. I.c.v. administration of the Zn(2+) chelator, EDTA saturated with equimolar Ca(2+) (CaEDTA), 15 min prior to ischemia attenuated subsequent Zn(2+) translocation into cortical neurons, and reduced infarct volume measured 3 days after ischemia. Although the protective effect of CaEDTA at this endpoint was substantial (about 70% infarct reduction), it was lost when insult severity was increased (from 30 to 60 min MCAO), or when infarct volume was measured at a much later time point (14 days instead of 3 days after ischemia). These data suggest that toxic Zn(2+) translocation, from presynaptic terminals to post-synaptic cell bodies, may accelerate the development of cerebral infarction following mild transient focal ischemia.

Electro-acupuncture exerts beneficial effects against cerebral ischemia and promotes the proliferation of neural progenitor cells in the cortical peri-infarct area through the Wnt/β-catenin signaling pathway

PubMed Central

CHEN, BIN; TAO, JING; LIN, YUKUN; LIN, RUHUI; LIU, WEILIN; CHEN, LIDIAN

2015-01-01

Electro-acupuncture (EA) is a novel therapy based on combining traditional acupuncture with modern electrotherapy, and it is currently being investigated as a treatment for ischemic stroke. In the present study, we aimed to investigate the mechanisms through which EA regulates the proliferation of neural progenitor cells (NPCs) in the cortical peri-infarct area after stroke. The neuroprotective effects of EA on ischemic rats were evaluated by determining the neurological deficit scores and cerebral infarct volumes. The proliferation of the NPCs and the activation of the Wnt/β-catenin signaling pathway in the cortical peri-infarct area were examined. Our results revealed that EA significantly alleviated neurological deficits, reduced the infarct volume and enhanced NPC proliferation [nestin/glial fibrillary acidic protein (GFAP)-double positive] in the cortex of rats subjected to middle cerebral artery occlusion (MCAO). Moreover, the Wnt1 and β-catenin mRNA and protein levels were increased, while glycogen synthase kinase-3 (GSK3) transcription was suppressed by EA. These results suggest that the upregulatory effects of EA on the Wnt/β-catenin signaling pathway may promote NPC proliferation in the cortical peri-infarct area after stroke, consequently providing a therapeutic effect against cerebral ischemia. PMID:26329606

Nebivolol prevents remodeling in a rat myocardial infarction model: an echocardiographic study.

PubMed

Mercanoğlu, Güldem Olguner; Pamukçu, Burak; Safran, Nurhas; Mercanoğlu, Fehmi; Fici, Francesco; Güngör, Mehmet

2010-02-01

Ventricular remodeling (VR) which develops after myocardial infarction (MI) plays an important role in progressive left ventricular dysfunction. We aimed to investigate the role of nebivolol treatment on VR after a MI in a rat ischemia-reperfusion model. Rats were divided into 3 groups of 12 each: sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI-nebivolol). Left ventricular (LV) diameters, volumes, and diastolic filling parameters were evaluated by echocardiography. On the 28th day, after recording the systemic and LV pressures and determining the plasma nitric oxide (NO) and peroxynitrite (ONOO-) levels , animals were sacrificed and heart, body and LV weights (HW, BW, LVW) were measured and infarct sizes were determined. Results were evaluated statistically by ANOVA for repeated measurements 3x3 factorial design with post-hoc Bonferroni test. After MI, while VR (an increase in LV diameters and volumes associated with a decrease in EF, FS and posterior wall thickness change (LWPc) was significant in MI-control rats (p<0.05 for; all comparisons) these changes were significantly less in MI-nebivolol group (p=0.08 and p=0.06 for EF and FS respectively). LV end diastolic pressure (LVEDP) was lower (p<0.005) and Delta+/- dp/dt's (p<0.05) were higher in MI-nebivolol group compared to MI-control animals. Although infarct sizes were similar in MI-induced groups (p=0.79); LVW/HW and HW/BW's were significantly greater in the MI-control group compared to sham-control (p<0.01 for all comparisons), these changes were not statistically significant in MI-nebivolol group. The increase in plasma NO and ONOO- levels were also prevented with nebivolol. Nebivolol therapy reduced the effects of VR in rats after MI. These beneficial effects were not related to its heart rate and blood pressure reducing effects. Nitric oxide regulatory action of this compound may contribute these beneficial effects on VR developed after MI.

Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study

PubMed Central

Wali, Bushra; Ishrat, Tauheed; Won, Soonmi; Stein, Donald G.

2014-01-01

Currently, the only approved treatment for ischaemic stroke is tissue plasminogen activator, a clot-buster. This treatment can have dangerous consequences if not given within the first 4 h after stroke. Our group and others have shown progesterone to be beneficial in preclinical studies of stroke, but a progesterone dose-response and time-window study is lacking. We tested male Sprague-Dawley rats (12 months old) with permanent middle cerebral artery occlusion or sham operations on multiple measures of sensory, motor and cognitive performance. For the dose-response study, animals received intraperitoneal injections of progesterone (8, 16 or 32 mg/kg) at 1 h post-occlusion, and subcutaneous injections at 6 h and then once every 24 h for 7 days. For the time-window study, the optimal dose of progesterone was given starting at 3, 6 or 24 h post-stroke. Behavioural recovery was evaluated at repeated intervals. Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume. Both 8 and 16 mg/kg doses of progesterone produced attenuation of infarct volume compared with the placebo, and improved functional outcomes up to 3 weeks after stroke on locomotor activity, grip strength, sensory neglect, gait impairment, motor coordination and spatial navigation tests. In the time-window study, the progesterone group exhibited substantial neuroprotection as late as 6 h after stroke onset. Compared with placebo, progesterone showed a significant reduction in infarct size with 3- and 6-h delays. Moderate doses (8 and 16 mg/kg) of progesterone reduced infarct size and improved functional deficits in our clinically relevant model of stroke. The 8 mg/kg dose was optimal in improving motor, sensory and memory function, and this effect was observed over a large therapeutic time window. Progesterone shows promise as a potential therapeutic agent and should be examined for safety and efficacy in a clinical trial for ischaemic stroke. PMID:24374329

Diffusion-weighted MRI determined cerebral embolic infarction following transcatheter aortic valve implantation: assessment of predictive risk factors and the relationship to subsequent health status.

PubMed

Fairbairn, Timothy A; Mather, Adam N; Bijsterveld, Petra; Worthy, Gillian; Currie, Stuart; Goddard, Anthony J P; Blackman, Daniel J; Plein, Sven; Greenwood, John P

2012-01-01

'Silent' cerebral infarction and stroke are complications of transcatheter aortic valve implantation (TAVI). To assess the occurrence of cerebral infarction, identify predictive risk factors and examine the impact on patient health-related quality of life (HRQoL). Cerebral diffusion weighted MRI of 31 patients with aortic stenosis undergoing CoreValve TAVI was carried out. HRQoL was assessed at baseline and at 30 days by SF-12v2 and EQ5D questionnaires. New cerebral infarcts occurred in 24/31 patients (77%) and stroke in 2 (6%). Stroke was associated with a greater number and volume of cerebral infarcts. Age (r=0.37, p=0.042), severity of atheroma (arch and descending aorta; r=0.91, p<0.001, r=0.69, p=0.001, respectively) and catheterisation time (r=0.45, p=0.02) were predictors of the number of new cerebral infarcts. HRQoL improved overall: SF-12v2 physical component summary increased significantly (32.4±6.2 vs 36.5±7.2; p=0.03) with no significant change in mental component summary (43.5±11.7 vs. 43.1±14.3; p=0.85). The EQ5D score and Visual Analogue Scale showed no significant change (0.56±0.26 vs. 0.59±0.31; p=0.70, and 54.2±19 vs. 58.2±24; p=0.43). Multiple small cerebral infarcts occurred in 77% of patients with TAVI. The majority of infarcts were 'silent' with clinical stroke being associated with a both higher infarct number and volume. Increased age and the severity of aortic arch atheroma were independent risk factors for the development of new cerebral infarcts. Overall HRQoL improved and there was no association between the number of new cerebral infarcts and altered health status.

Computed Tomography Perfusion Improves Diagnostic Accuracy in Acute Posterior Circulation Stroke.

PubMed

Sporns, Peter; Schmidt, Rene; Minnerup, Jens; Dziewas, Rainer; Kemmling, André; Dittrich, Ralf; Zoubi, Tarek; Heermann, Philipp; Cnyrim, Christian; Schwindt, Wolfram; Heindel, Walter; Niederstadt, Thomas; Hanning, Uta

2016-01-01

Computed tomography perfusion (CTP) has a high diagnostic value in the detection of acute ischemic stroke in the anterior circulation. However, the diagnostic value in suspected posterior circulation (PC) stroke is uncertain, and whole brain volume perfusion is not yet in widespread use. We therefore studied the additional value of whole brain volume perfusion to non-contrast CT (NCCT) and CT angiography source images (CTA-SI) for infarct detection in patients with suspected acute ischemic PC stroke. This is a retrospective review of patients with suspected stroke in the PC in a database of our stroke center (n = 3,011) who underwent NCCT, CTA and CTP within 9 h after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and pc-ASPECTS locations of ischemia. Three imaging models - A (NCCT), B (NCCT + CTA-SI) and C (NCCT + CTA-SI + CTP) - were compared with regard to the misclassification rate relative to gold standard (infarction in follow-up imaging) using the McNemar's test. Of 3,011 stroke patients, 267 patients had a suspected stroke in the PC and 188 patients (70.4%) evidenced a PC infarct on follow-up imaging. The sensitivity of Model C (76.6%) was higher compared with that of Model A (21.3%) and Model B (43.6%). CTP detected significantly more ischemic lesions, especially in the cerebellum, posterior cerebral artery territory and thalami. Our findings in a large cohort of consecutive patients show that CTP detects significantly more ischemic strokes in the PC than CTA and NCCT alone. © 2016 S. Karger AG, Basel.

Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis.

PubMed

Dong, Mei-Xue; Hu, Qing-Chuan; Shen, Peng; Pan, Jun-Xi; Wei, You-Dong; Liu, Yi-Yun; Ren, Yi-Fei; Liang, Zi-Hong; Wang, Hai-Yang; Zhao, Li-Bo; Xie, Peng

2016-01-01

Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke. Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger's test were obtained to detect publication bias. We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate. This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA.

Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis

PubMed Central

Wei, You-Dong; Liu, Yi-Yun; Ren, Yi-Fei; Liang, Zi-Hong; Wang, Hai-Yang; Zhao, Li-Bo; Xie, Peng

2016-01-01

Background and Purpose Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke. Methods Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger’s test were obtained to detect publication bias. Results We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate. Conclusions This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA. PMID:27387385

Reproductive age modulates the impact of focal ischemia on the forebrain as well as the effects of estrogen treatment in female rats

PubMed Central

Selvamani, Amutha; Sohrabji, Farida

2009-01-01

While human observational studies and animal studies report a neuroprotective role for estrogen therapy in stroke, the multicenter placebo-controlled Women's Health Initiative (WHI) study concluded that hormone therapy increased the risk for stroke in postmenopausal women. The present study therefore tested the hypothesis that estrogen replacement would increase the severity of a stroke-like injury in females when this replacement occurs after a prolonged hypoestrogenic period, such as the menopause or reproductive senescence, but not when given to females that were normally cycling immediately prior to the hormone replacement. Two groups of female rats were used: multiparous females with normal but lengthened estrus cycles (mature adults), and older multiparous females currently in a persistent acyclic state (reproductive senescent). Animals were either used intact, or were bilaterally ovariectomized and immediately replaced with a 17β-estradiol pellet or control pellet. Animals were subject to a forelimb placing test (a test for sensorimotor deficit) and thereafter to middle cerebral artery occlusion (MCAo) by stereotaxic injection of the vasoconstrictive peptide endothelin-1, adjacent to the MCA. One week after stroke, behavioral tests were performed again. Cortical and striatal infarct volume, measured from brain slices, was significantly greater in intact reproductive senescent females as compared to intact mature adults. Furthermore, estrogen treatment to ovariectomized mature adult females significantly reduced the cortical infarct volume. Paradoxically, estrogen treatment to ovariectomized reproductive senescent females significantly increased cortical and striatal infarct volumes as compared to control pellet replaced senescent females. Significant post-stroke behavioral deficit was observed in all groups on the side contralateral to the lesion, while senescent females also exhibited deficits on the ipsilateral side, in the cross-midline forelimb placement test. Using an animal model that approximates the natural ovarian aging process, these findings strongly support the hypothesis that the effectiveness of estrogen therapy in protecting brain health may depend critically on the time of initiation with respect to a female's reproductive status. PMID:18829137

Randomized placebo controlled trial evaluating the safety and efficacy of single low-dose intracoronary insulin-like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI).

PubMed

Caplice, Noel M; DeVoe, Mary C; Choi, Janet; Dahly, Darren; Murphy, Theodore; Spitzer, Ernest; Van Geuns, Robert; Maher, Michael M; Tuite, David; Kerins, David M; Ali, Mohammed T; Kalyar, Imtiaz; Fahy, Eoin F; Khider, Wisam; Kelly, Peter; Kearney, Peter P; Curtin, Ronan J; O'Shea, Conor; Vaughan, Carl J; Eustace, Joseph A; McFadden, Eugene P

2018-06-01

Residual and significant postinfarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models, low-dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodeling effects. We studied the safety and efficacy of immediate post-PCI low-dose intracoronary IGF1 infusion in STEMI patients. Using a double-blind, placebo-controlled, multidose study design, we randomized 47 STEMI patients with significantly reduced (≤40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n = 15), 1.5 ng IGF1 (n = 16), or 15 ng IGF1 (n = 16). All received optimal medical therapy. Safety end points were freedom from hypoglycemia, hypotension, or significant arrhythmias within 1 hour of therapy. The primary efficacy end point was LVEF, and secondary end points were LV volumes, mass, stroke volume, and infarct size at 2-month follow-up, all assessed by magnetic resonance imaging. Treatment effects were estimated by analysis of covariance adjusted for baseline (24 hours) outcome. No significant differences in safety end points occurred between treatment groups out to 30 days (χ 2 test, P value = .77). There were no statistically significant differences in baseline (24 hours post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups, with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5 ng IGF1, treatment with 15 ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (P = .018), LV mass (P = .004), and stroke volume (P = .016). Late gadolinium enhancement (±SD) at 2 months was lower in 15 ng IGF1 (34.5 ± 29.6 g) compared to placebo (49.1 ± 19.3 g) or 1.5 ng IGF1 (47.4 ± 22.4 g) treated patients, although the result was not statistically significant (P = .095). In this pilot trial, low-dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose-dependent benefit on post-MI remodeling that may warrant further study. Copyright © 2018. Published by Elsevier Inc.

L-NAME reduces infarction, neurological deficit and blood-brain barrier disruption following cerebral ischemia in mice.

PubMed

Ding-Zhou, Li; Marchand-Verrecchia, Catherine; Croci, Nicole; Plotkine, Michel; Margaill, Isabelle

2002-12-20

The role of nitric oxide (NO) in the development of post-ischemic cerebral infarction has been extensively examined, but fewer studies have investigated its role in other outcomes. In the present study, we first determined the temporal evolution of infarct volume, NO production, neurological deficit and blood-brain barrier disruption in a model of transient focal cerebral ischemia in mice. We then examined the effect of the nonselective NO-synthase inhibitor N(omega)-nitro-L-arginine-methylester (L-NAME). L-NAME given at 3 mg/kg 3 h after ischemia reduced by 20% the infarct volume and abolished the increase in brain NO production evaluated by its metabolites (nitrites/nitrates) 48 h after ischemia. L-NAME with this protocol also reduced the neurological deficit evaluated by the grip test and decreased by 65% the extravasation of Evans blue, an index of blood-brain barrier breakdown. These protective activities of L-NAME suggest that NO has multiple deleterious effects in cerebral ischemia.

Automated quantification of myocardial infarction from MR images by accounting for partial volume effects: animal, phantom, and human study.

PubMed

Heiberg, Einar; Ugander, Martin; Engblom, Henrik; Götberg, Matthias; Olivecrona, Göran K; Erlinge, David; Arheden, Håkan

2008-02-01

Ethics committees approved human and animal study components; informed written consent was provided (prospective human study [20 men; mean age, 62 years]) or waived (retrospective human study [16 men, four women; mean age, 59 years]). The purpose of this study was to prospectively evaluate a clinically applicable method, accounting for the partial volume effect, to automatically quantify myocardial infarction from delayed contrast material-enhanced magnetic resonance images. Pixels were weighted according to signal intensity to calculate infarct fraction for each pixel. Mean bias +/- variability (or standard deviation), expressed as percentage left ventricular myocardium (%LVM), were -0.3 +/- 1.3 (animals), -1.2 +/- 1.7 (phantoms), and 0.3 +/- 2.7 (patients), respectively. Algorithm had lower variability than dichotomous approach (2.7 vs 7.7 %LVM, P < .01) and did not differ from interobserver variability for bias (P = .31) or variability (P = .38). The weighted approach provides automatic quantification of myocardial infarction with higher accuracy and lower variability than a dichotomous algorithm. (c) RSNA, 2007.

CMR imaging of edema in myocardial infarction using cine balanced steady-state free precession.

PubMed

Kumar, Andreas; Beohar, Nirat; Arumana, Jain Mangalathu; Larose, Eric; Li, Debiao; Friedrich, Matthias G; Dharmakumar, Rohan

2011-12-01

The aim of this study was to investigate the capabilities of balanced steady-state free precession (bSSFP) cardiac magnetic resonance imaging as a novel cine imaging approach for characterizing myocardial edema in animals and patients after reperfused myocardial infarction. Current cardiac magnetic resonance methods require 2 separate scans for assessment of myocardial edema and cardiac function. Mini-pigs (n = 13) with experimentally induced reperfused myocardial infarction and patients with reperfused ST-segment elevation myocardial infarction (n = 26) underwent cardiac magnetic resonance scans on days 2 to 4 post-reperfusion. Cine bSSFP, T2-weighted short TI inversion recovery (T2-STIR), and late gadolinium enhancement were performed at 1.5-T. Cine bSSFP and T2-STIR images were acquired with a body coil to mitigate surface coil bias. Signal, contrast, and the area of edema were compared. Additional patients (n = 10) were analyzed for the effect of microvascular obstruction on bSSFP. A receiver-operator characteristic analysis was performed to assess the accuracy of edema detection. An area of hyperintense bSSFP signal consistent with edema was observed in the infarction zone (contrast-to-noise ratio: 37 ± 13) in all animals and correlated well with the area of late gadolinium enhancement (R = 0.83, p < 0.01). In all patients, T2-STIR and bSSFP images showed regional hyperintensity in the infarction zone. Normalized contrast-to-noise ratios were not different between T2-STIR and bSSFP. On a slice basis, the volumes of hyperintensity on T2-STIR and bSSFP images correlated well (R = 0.86, p < 0.001), and their means were not different. When compared with T2-STIR, bSSFP was positive for edema in 25 of 26 patients (96% sensitivity) and was negative in all controls (100% specificity). All patients with microvascular obstruction showed a significant reduction of signal in the subendocardial infarction zone compared with infarcted epicardial tissue without microvascular obstruction (p < 0.05). Myocardial edema from ST-segment elevation myocardial infarction can be detected using cine bSSFP imaging with image contrast similar to T2-STIR. This new imaging approach allows evaluation of cardiac function and edema simultaneously, thereby reducing patient scan time and increasing efficiency. Further work is necessary to optimize edema contrast in bSSFP images. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

CT Perfusion in Acute Stroke: "Black Holes" on Time-to-Peak Image Maps Indicate Unsalvageable Brain.

PubMed

Meagher, Ruairi; Shankar, Jai Jai Shiva

2016-11-01

CT perfusion is becoming important in acute stroke imaging to determine optimal patient-management strategies. The purpose of this study was to examine the predictive value of time-to-peak image maps and, specifically, a phenomenon coined a "black hole" for assessing infarcted brain tissue at the time of scan. Acute stroke patients were screened for the presence of black holes and their follow-up imaging (noncontrast CT or MR) was reviewed to assess for infarcted brain tissue. Of the 23 patients with signs of acute ischemia on CT perfusion, all had black holes. The black holes corresponded with areas of infarcted brain on follow-up imaging (specificity 100%). Black holes demonstrated significantly lower cerebral blood volumes (P < .001) and cerebral blood flow (P < .001) compared to immediately adjacent tissue. Black holes on time-to-peak image maps represent areas of unsalvageable brain. Copyright © 2016 by the American Society of Neuroimaging.

MR images of mouse brain using clinical 3T MR scanner and 4CH-Mouse coil

NASA Astrophysics Data System (ADS)

Lim, Soo Mee; Park, Eun Mi; Lyoo, In Kyoon; Lee, Junghyun; Han, Bo Mi; Lee, Jeong Kyong; Lee, Su Bin

2015-07-01

Objectives: Although small-bore high-field magnets are useful for research in small rodent models,this technology, however, has not been easily accessible to most researchers. This current study, thus,tried to evaluate the usability of 4CH-Mouse coil (Philips Healthcare, Best, the Netherlands) forpreclinical investigations in clinical 3T MR scan environment. We evaluated the effects of ischemicpreconditioning (IP) in the mouse stroke model with clinical 3T MR scanner and 4CH-Mouse coil. Materials and Methods: Experiments were performed on male C57BL/6 mice that either received the IP or sham operation (control). Three different MR sequences including diffusion weighted images (DWI), T2-weighted images (T2WI), and fluid attenuated inversion recovery (FLAIR) were performed on the mouse brains following 24, 72 hours of middle cerebral artery occlusion (MCAO) and analyzed for infarct lesions. Results: The images showed that the IP-treated mouse brains had significantly smaller infarct volumes compared to the control group. Of the MR sequences employed, the T2WI showed the highest level of correlations with postmortem infarct volume measurements. Conclusions: The clinical 3T MR scanner turned out to have a solid potential as a practical tool for imaging small animal brains. MR sequences including DWI, T2WI, FLAIR were obtained with acceptable resolution and in a reasonable time constraint in evaluating a mouse stroke model brain.

Gated-SPECT myocardial perfusion imaging as a complementary technique to magnetic resonance imaging in chronic myocardial infarction patients.

PubMed

Cuberas-Borrós, Gemma; Pineda, Victor; Aguadé-Bruix, Santiago; Romero-Farina, Guillermo; Pizzi, M Nazarena; de León, Gustavo; Castell-Conesa, Joan; García-Dorado, David; Candell-Riera, Jaume

2013-09-01

The aim of this study was to compare magnetic resonance and gated-SPECT myocardial perfusion imaging in patients with chronic myocardial infarction. Magnetic resonance imaging and gated-SPECT were performed in 104 patients (mean age, 61 [12] years; 87.5% male) with a previous infarction. Left ventricular volumes and ejection fraction and classic late gadolinium enhancement viability criteria (<75% transmurality) were correlated with those of gated-SPECT (uptake >50%) in the 17 segments of the left ventricle. Motion, thickening, and ischemia on SPECT were analyzed in segments showing nonviable tissue or equivocal enhancement features (50%-75% transmurality). A good correlation was observed between the 2 techniques for volumes, ejection fraction (P<.05), and estimated necrotic mass (P<.01). In total, 82 of 264 segments (31%) with >75% enhancement had >50% single SPECT uptake. Of the 106 equivocal segments on magnetic resonance imaging, 68 (64%) had >50% uptake, 41 (38.7%) had normal motion, 46 (43.4%) had normal thickening, and 17 (16%) had ischemic criteria on SPECT. A third of nonviable segments on magnetic resonance imaging showed >50% uptake on SPECT. Gated-SPECT can be useful in the analysis of motion, thickening, and ischemic criteria in segments with questionable viability on magnetic resonance imaging. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Oleuropein, a natural extract from plants, offers neuroprotection in focal cerebral ischemia/reperfusion injury in mice.

PubMed

Yu, Hailong; Liu, Peipei; Tang, Hui; Jing, Jian; Lv, Xiang; Chen, Lanlan; Jiang, Li; Xu, Jun; Li, Jun

2016-03-15

Oleuropein (OLE) was found to have anti-inflammatory and anti-oxidant effects. The latest study has shown that it can resist myocardial injury that follows an acute myocardial infarction and can rescue impaired spinal nerve cells. In this study, we investigated the neuroprotective effects of OLE on cerebral ischemia and reperfusion injury in a middle cerebral artery occlusion model in mice.OLE (100 mg/kg) was injected intraperitoneally 1h before ischemia. We found that the volume of cerebral infarction was significantly reduced after 75 min of ischemia and 24 h of reperfusion compared with the I/R (ischemia/reperfusion) group. This protective function occurred in a dose-dependent manner. We also found that treatment with OLE could reduce the cerebral infarct volume. The neuroprotective effect was prolonged from 2 h to 4 h when we injected OLE intracerebroventricularly after reperfusion. We then found that OLE can decrease the level of cleavedcaspase-3, an important marker of apoptosis, in the ischemic mouse brain. Finally, we explored the role of OLE in providing anti-apoptotic effects through the increased expression of Bcl-2 and the decreased expression of Bax, which are important markers in apoptosis. As shown above, the function and safety of OLE in cardiovascular disease may indicate that it is a potential therapeutic for stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

An analysis of Methylenetetrahydrofolate reductase and Glutathione S-transferase omega-1 genes as modifiers of the cerebral response to ischemia

PubMed Central

Peddareddygari, Leema Reddy; Dutra, Ana Virginia; Levenstien, Mark A; Sen, Souvik; Grewal, Raji P

2009-01-01

Background Cerebral ischemia involves a series of reactions which ultimately influence the final volume of a brain infarction. We hypothesize that polymorphisms in genes encoding proteins involved in these reactions could act as modifiers of the cerebral response to ischemia and impact the resultant stroke volume. The final volume of a cerebral infarct is important as it correlates with the morbidity and mortality associated with non-lacunar ischemic strokes. Methods The proteins encoded by the methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase omega-1 (GSTO-1) genes are, through oxidative mechanisms, key participants in the cerebral response to ischemia. On the basis of these biological activities, they were selected as candidate genes for further investigation. We analyzed the C677T polymorphism in the MTHFR gene and the C419A polymorphism in the GSTO-1 gene in 128 patients with non-lacunar ischemic strokes. Results We found no significant association of either the MTHFR (p = 0.72) or GSTO-1 (p = 0.58) polymorphisms with cerebral infarct volume. Conclusion Our study shows no major gene effect of either the MTHFR or GSTO-1 genes as a modifier of ischemic stroke volume. However, given the relatively small sample size, a minor gene effect is not excluded by this investigation. PMID:19624857

Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and 18F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia

PubMed Central

Cockburn, Neil; Kovacs, Michael

2016-01-01

CT Perfusion (CTP) derived cerebral blood flow (CBF) thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to 18F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1) was injected into the brain of Duroc-Cross pigs (n = 11) through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of 18F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155–180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and 18F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min-1·100g-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion. PMID:27347877

Intracoronary Administration of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells Improves Myocardial Perfusion But Not Left Ventricle Function, in a Translational Model of Acute Myocardial Infarction.

PubMed

Bobi, Joaquim; Solanes, Núria; Fernández-Jiménez, Rodrigo; Galán-Arriola, Carlos; Dantas, Ana Paula; Fernández-Friera, Leticia; Gálvez-Montón, Carolina; Rigol-Monzó, Elisabet; Agüero, Jaume; Ramírez, José; Roqué, Mercè; Bayés-Genís, Antoni; Sánchez-González, Javier; García-Álvarez, Ana; Sabaté, Manel; Roura, Santiago; Ibáñez, Borja; Rigol, Montserrat

2017-05-03

Autologous adipose tissue-derived mesenchymal stem cells (ATMSCs) therapy is a promising strategy to improve post-myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long-term effects and the mechanisms involved in allogeneic ATMSCs administration on myocardial performance. Thirty-eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. After reperfusion, allogeneic ATMSCs or culture medium (vehicle) were intracoronarily administered. Follow-ups were performed at short (2 days after acute myocardial infarction vehicle-treated, n=10; ATMSCs-treated, n=9) or long term (60 days after acute myocardial infarction vehicle-treated, n=7; ATMSCs-treated, n=7). At short term, infarcted myocardium analysis showed reduced apoptosis in the ATMSCs-treated animals (48.6±6% versus 55.9±5.7% in vehicle; P =0.017); enhancement of the reparative process with up-regulated vascular endothelial growth factor, granulocyte macrophage colony-stimulating factor, and stromal-derived factor-1α gene expression; and increased M2 macrophages (67.2±10% versus 54.7±10.2% in vehicle; P =0.016). In long-term groups, increase in myocardial perfusion at the anterior infarct border was observed both on day-7 and day-60 cardiac magnetic resonance studies in ATMSCs-treated animals, compared to vehicle (87.9±28.7 versus 57.4±17.7 mL/min per gram at 7 days; P =0.034 and 99±22.6 versus 43.3±14.7 22.6 mL/min per gram at 60 days; P =0.0001, respectively). At day 60, higher vascular density was detected at the border zone in the ATMSCs-treated animals (118±18 versus 92.4±24.3 vessels/mm 2 in vehicle; P =0.045). Cardiac magnetic resonance-measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point. In this porcine acute myocardial infarction model, allogeneic ATMSCs-based therapy was associated with increased cardioprotective and reparative mechanisms and with better cardiac magnetic resonance-measured perfusion. No effect on left ventricular volumes or ejection fraction was observed. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Brain tissue volumes in the general elderly population. The Rotterdam Scan Study.

PubMed

Ikram, M Arfan; Vrooman, Henri A; Vernooij, Meike W; van der Lijn, Fedde; Hofman, Albert; van der Lugt, Aad; Niessen, Wiro J; Breteler, Monique M B

2008-06-01

We investigated how volumes of cerebrospinal fluid (CSF), grey matter (GM) and white matter (WM) varied with age, sex, small vessel disease and cardiovascular risk factors in the Rotterdam Scan Study. Participants (n=490; 60-90 years) were non-demented and 51.0% had hypertension, 4.9% had diabetes mellitus, 17.8% were current smoker and 54.0% were former smoker. We segmented brain MR-images into GM, normal WM, white matter lesion (WML) and CSF. Brain infarcts were rated visually. Volumes were expressed as percentage of intra-cranial volume. With increasing age, volumes of total brain, normal WM and total WM decreased; that of GM remained unchanged; and that of WML increased, in both men and women. Excluding persons with infarcts did not alter these results. Persons with larger load of small vessel disease had smaller brain volume, especially normal WM volume. Diastolic blood pressure, diabetes mellitus and current smoking were also related to smaller brain volume. In the elderly, higher age, small vessel disease and cardiovascular risk factors are associated with smaller brain volume, especially WM volume.

Relationship between left ventricular mechanics and low free triiodothyronine levels after myocardial infarction: a prospective study.

PubMed

Jankauskienė, Edita; Orda, Paulius; Barauskienė, Greta; Mickuvienė, Narseta; Brožaitienė, Julija; Vaškelytė, Jolanta Justina; Bunevičius, Robertas

2016-04-01

Low free triiodothyronine (fT3) levels following acute myocardial infarction (AMI) are associated with greater impairment in cardiac mechanics compared with patients with AMI who have normal values of thyroid hormones. The objectives are to investigate left ventricular (LV) function and mechanics during a 6-month follow-up after myocardial infarction and to evaluate their prognostic implication using two-dimensional (2D) echocardiography and 2D speckle-tracking echocardiography in patients with low fT3 levels. The study design is prospective cohort study. One hundred forty patients with first-onset AMI were grouped according to serum fT3 levels: low fT3 group (fT3 <3.2 pmol/L; n = 44) and control group (fT3 >3.2 pmol/L; n = 96). Low levels of fT3 were associated with greater LV diameters and LV end-diastolic volume, and decreased systolic LV function. Systolic apical and basal rotation, peak systolic global longitudinal strain and strain rate, and LV twist and torsion were significantly decreased in the low fT3 group. The prognostic implication for predicting low fT3 levels was evaluated using ROC analysis. LV end-diastolic diameter index is the most sensitive (94.12 %), but has low specificity (37.93 %; area = 0.659, p = 0.01). By contrast, LV end-systolic volume is the most specific (94.03 %), but has low sensitivity (26.32 %; area = 0.594, p = 0.04). Low fT3 levels are significantly associated with worse LV mechanics. Low fT3 levels are important for prediction of LV structure, function, rotation, and deformation parameters during the late post-myocardial infarction period.

Association of Left Atrial Enlargement with Cortical Infarction in Subjects with Patent Foramen Ovale.

PubMed

Lee, Mi Ji; Park, Sung-Ji; Yoon, Chang Hyo; Hwang, Ji-Won; Ryoo, Sookyung; Kim, Suk Jae; Kim, Gyeong-Moon; Chung, Chin-Sang; Lee, Kwang Ho; Bang, Oh Young

2016-09-01

Left atrial dysfunction has been reported in patients with patent foramen ovale (PFO). Here we investigated the role of left atrial dysfunction in the development of embolic stroke in patients with PFO. We identified consecutive patients with embolic stroke of undetermined sources except for PFO (PFO+ESUS). Healthy subjects with PFO served as controls (PFO+control). A stratified analysis by 10-year age group and an age- and sex- matching analysis were performed to compare echocardiographic markers between groups. In the PFO+ESUS group, infarct patterns of PFO-related stroke were determined (cortical vs. cortico-subcortical) and analyzed in correlation with left atrial function parameters. A total of 118 patients and 231 controls were included. The left atrial volume indices (LAVIs) of the PFO+ESUS patients were higher than those of the PFO+controls in age groups of 40-49, 50-59, and 60-69 years ( P <0.001, P =0.003, and P =0.027, respectively), and in the age- and sex-matched analysis ( P =0.001). In the PFO+ESUS patients, a higher (>28 mL/m 2 ) LAVI was more associated with the cortical infarct pattern ( P =0.043 for an acute infarction and P =0.024 for a chronic infarction, both adjusted for age and shunt amount). The degree of right-to-left shunting was not associated with infarct patterns, but with the posterior location of acute infarcts ( P =0.028). Left atrial enlargement was associated with embolic stroke in subjects with PFO. Left atrial physiology might contribute to the development of PFO-related stroke and need to be taken into consideration for optimal prevention of PFO-related stroke.

Treatment with the CC chemokine-binding protein Evasin-4 improves post-infarction myocardial injury and survival in mice.

PubMed

Braunersreuther, Vincent; Montecucco, Fabrizio; Pelli, Graziano; Galan, Katia; Proudfoot, Amanda E; Belin, Alexandre; Vuilleumier, Nicolas; Burger, Fabienne; Lenglet, Sébastien; Caffa, Irene; Soncini, Debora; Nencioni, Alessio; Vallée, Jean-Paul; Mach, François

2013-10-01

Chemokines trigger leukocyte trafficking and are implicated in cardiovascular disease pathophysiology. Chemokine-binding proteins, called "Evasins" have been shown to inhibit both CC and CXC chemokine-mediated bioactivities. Here, we investigated whether treatment with Evasin-3 (CXC chemokine inhibitor) and Evasin-4 (CC chemokine inhibitor) could influence post-infarction myocardial injury and remodelling. C57Bl/6 mice were submitted in vivo to left coronary artery permanent ligature and followed up for different times (up to 21 days). After coronary occlusion, three intraperitoneal injections of 10 μg Evasin-3, 1 μg Evasin-4 or equal volume of vehicle (PBS) were performed at 5 minutes, 24 hours (h) and 48 h after ischaemia onset. Both anti-chemokine treatments were associated with the beneficial reduction in infarct size as compared to controls. This effect was accompanied by a decrease in post-infarction myocardial leukocyte infiltration, reactive oxygen species release, and circulating levels of CXCL1 and CCL2. Treatment with Evasin-4 induced a more potent effect, abrogating the inflammation already at one day after ischaemia onset. At days 1 and 21 after ischaemia onset, both anti-chemokine treatments failed to significantly improve cardiac function, remodelling and scar formation. At 21-day follow-up, mouse survival was exclusively improved by Evasin-4 treatment when compared to control vehicle. In conclusion, we showed that the selective inhibition of CC chemokines (i.e. CCL5) with Evasin-4 reduced cardiac injury/inflammation and improved survival. Despite the inhibition of CXC chemokine bioactivities, Evasin-3 did not affect mouse survival. Therefore, early inhibition of CC chemokines might represent a promising therapeutic approach to reduce the development of post-infarction heart failure in mice.

Breviscapine confers a neuroprotective efficacy against transient focal cerebral ischemia by attenuating neuronal and astrocytic autophagy in the penumbra.

PubMed

Pengyue, Zhang; Tao, Guo; Hongyun, He; Liqiang, Yang; Yihao, Deng

2017-06-01

Breviscapine is a flavonoid derived from a traditional Chinese herb Erigerin breviscapus (Vant.) Hand-Mazz, and has been extensively used in clinical treatment for cerebral stroke in China, but the underlying pharmacological mechanisms are still unclear. In present study, we investigated whether breviscapine could confer a neuroprotection against cerebral ischemia injury by targeting autophagy mechanisms. A cerebral stroke model in Sprague-Dawley rats was prepared by middle cerebral artery occlusion (MCAO), rats were then randomly divided into 5 groups: MCAO+Bre group, rats were treated with breviscapine; MCAO+Tat-Beclin-1 group, animals were administrated with specific autophagy inducer Tat-Beclin-1; MCAO+Bre+Tat-Beclin-1 group, rats were treated with both breviscapine and Tat-Beclin-1, MCAO+saline group, rats received the same volume of physiological saline, and Sham surgery group. The autophagy levels in infarct penumbra were evaluated by western blotting, real-time PCR and immunofluorescence 7days after the insult. Meanwhile, infarct volume, brain water content and neurological deficit score were assessed. The results illustrated that the infarct volume, brain water content and neurofunctional deficiency were significantly reduced by 7days of breviscapine treatment in MCAO+Bre group, compared with those in MCAO+saline group. Meanwhile, the western blotting, quantitative PCR and immunofluorescence showed that the autophagy in both neurons and astrocytes at the penumbra were markedly attenuated by breviscapine admininstration. Moreover, these pharmacological effects of breviscapine could be counteracted by autophagy inducer Tat-Beclin-1. Our study suggests that breviscapine can provide a neuroprotection against transient focal cerebral ischemia, and this biological function is associated with attenuating autophagy in both neurons and astrocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Study of neuron-protective effect and mechanism of neuregulin1β against cerebral ischemia reperfusion-induced injury in rats].

PubMed

Ji, Y Q; Zhang, R; Teng, L; Li, H Y; Guo, Y L

2017-07-18

Objective: Thecurrent study is to explore the neuron-protective mechanism of neuregulin1β (NRG1β) in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) through inhibiting the c-Jun phosphorylation. Methods: After 24 h of MCAO/R (referring to Longa's method), neurobehavioral function was measured by modified neurological severity score (mNSS) test; the cerebral infarction volume was detected by triphenyltetrazolium chloride (TTC) staining; the blood brain barrier (BBB) permeability was measured by Evans Blue (EB); the neuron morphology of brain tissue was observed by Nissl stain; the ultra-structures of the neurons were observed by transmission electron microscopy (TEM); the apoptotic neurons were counted by in situ cell death detection kit colocalized with NeuN; the expressions of phospho-c-Jun was determined by immunofluorescent labeling and Western blot analysis. Results: Compared with the sham-operation rats, the rats receiving MCAO/R showed increased mNSS (9.7±1.2), cerebral infarction volume (41.4±3.0)%, permeability of BBB, deformation of neurons, ischemia-induced apoptosis (0.63±0.04), and enhanced expression of phospho-c-Jun protein (0.90±0.07) (all P <0.05). Our data indicated that NRG1β attenuated neurologic deficits (6.4±0.9), decreased the cerebral infarction volume (10.4±0.5), reduced EB extravasation (1.55±0.13) and the deformation of neurons, protected the ultra-structure of neurons, blocked ischemia-induced apoptosis (0.23±0.02), through down-regulated phospho-c-Jun expression (0.40±0.03) in MCAO/R rats ( P <0.05). Conclusion: NRG1β exerts neuron-protective effects against ischemia reperfusion-induced injury in rats through inhibiting the c-Jun phosphorylation.

Probucol plus cilostazol attenuate hypercholesterolemia‑induced exacerbation in ischemic brain injury via anti-inflammatory effects.

PubMed

Kim, Ji Hyun; Hong, Ki Whan; Bae, Sun Sik; Shin, Yong-Il; Choi, Byung Tae; Shin, Hwa Kyoung

2014-09-01

Probucol, a lipid-lowering agent with anti-oxidant properties, is involved in protection against atherosclerosis, while cilostazol, an antiplatelet agent, has diverse neuroprotective properties. In this study, we investigated the anti-inflammatory effects of probucol and cilostazol on focal cerebral ischemia with hypercholesterolemia. Apolipoprotein E (ApoE) knockout (KO) mice were fed a high-fat diet (HFD) with or without 0.3% probucol and/or 0.2% cilostazol for 10 weeks. To assess the protective effects of the combined therapy of probucol and cilostazol on ischemic injury, the mice received 40 min of middle cerebral artery occlusion (MCAO). Infarct volumes, neurobehavioral deficits and neuroinflammatory mediators were subsequently evaluated 48 h after reperfusion. Probucol alone and probucol plus cilostazol significantly decreased total- and low-density lipoprotein (LDL)-cholesterol in ApoE KO with HFD. MCAO resulted in significantly larger infarct volumes in ApoE KO mice provided with HFD compared to those fed a regular diet, although these volumes were significantly reduced in the probucol plus cilostazol group. Consistent with a smaller infarct size, probucol alone and the combined treatment of probucol and cilostazol improved neurological and motor function. In addition, probucol alone and probucol plus cilostazol decreased MCP-1 expression and CD11b and GFAP immuno-reactivity in the ischemic cortex. These findings suggested that the inhibitory effects of probucol plus cilostazol in MCP-1 expression in the ischemic brain with hypercholesterolemia allowed the identification of one of the mechanisms responsible for anti-inflammatory action. Probucol plus cilostazol may therefore serve as a therapeutic strategy for reducing the impact of stroke in hypercholesterolemic subjects.

Study on the effects of parecoxib on hypothalamus orexin neuron of cerebral infarction rats.

PubMed

Li, F-T; Yao, C-H; Yao, L; Huo, Z-F; Liu, J

2018-03-01

To explore the effect of parecoxib on cerebral infarction in rats and the regulatory mechanism on hypothalamus orexin neurons (orexin) and protein expression. 60 SD male rats were randomly divided into sham operation group, model group and treatment group (20 rats in each group). Cerebral infarction model was established by modified Longa method. Rats in the treatment group were given parecoxib (2.5 mg kg-1) in tail by intravenous injection, while both the sham operation group and the model group were given the equal volume of sterile PBS solution in the tail vein. Continuous intervention of 72h was carried out in the three groups. Immunofluorescence staining and Western blot were used to detect the expression of orexin neurons and orexin protein in the hypothalamus of rats, respectively. Immunofluorescence staining showed that the number of orexin positive cells in the model group was significantly less than that in the sham-operated group (p < 0.01). After treatment intervention, the number of orexin positive cells in the hypothalamus was significantly increased compared to that in model group (p < 0.01). Western blot analysis showed that compared with sham operation group, the expression of orexin in the hypothalamus of model group was significantly decreased (p < 0.01), whereas the expression of orexin protein was significantly elevated after parecoxib intervention (p < 0.01). Parecoxib plays a therapeutic effect on cerebral infarction by up-regulating the orexin neuron.

Caspase-3 inhibitor prevents the apoptosis of brain tissue in rats with acute cerebral infarction.

PubMed

Sun, Yuhua; Xu, Yuming; Geng, Lijiao

2015-07-01

The aim of the present study was to investigate the effect of the caspase-3 inhibitor z-DEVD-fmk on the apoptosis of the brain tissues of rats with acute cerebral infarction. Middle cerebral artery occlusion was used to establish a rat model of infarction, and the rats were randomly divided into a sham group (n=15), model group (n=15) and treatment group (n=15). z-DEVD-fmk (2.5 µg/kg) was injected into the intracranial artery of rats in the treatment group, while the same volume of phosphate-buffered saline solution was administered to the rats of the sham and model groups. After 48 h, all rats were sacrificed and their brain tissues were removed. The caspase-3 mRNA level, protein level and activity, brain cell apoptosis index and infarction scope of the three groups were analyzed. Neurological impairment was also assessed. At 48 h after model establishment, the caspase-3 mRNA and protein levels in the brain tissues of the model group were significantly higher than those of the sham group, and those in the treatment group were significantly lower than those in the model group (P<0.05); however, they remained significantly higher than those in the sham group. Caspase-3 activity in the model group was significantly higher than that in the sham group, and treatment with the caspase-3 inhibitor significantly reduced caspase-3 activity compared with that in the model group (P<0.05). The apoptosis index and infarction scope in the model and treatment groups were significantly increased compared with those in the sham group, and were significantly lower in the treatment group than in the model group (P<0.05). The neurological impairment of rats in the model and treatment groups was increased significantly compared with that in the sham group, and the treatment group exhibited a significantly lower level of neurological impairment than the model group (P<0.05). In conclusion, the caspase-3 inhibitor z-DEVD-fmk effectively inhibited apoptosis and delayed the necrosis of brain tissue cells in rats with acute cerebral infarction, and had certain protective effects on brain tissue.

NEUROIMAGING CHARACTERISTICS AND POST-STROKE FATIGUE WITHIN THE FIRST 6 MONTHS AFTER ISCHEMIC STROKES.

PubMed

Delva, M; Delva, I

2017-10-01

Aim - identify neuroimaging characteristics associated with different post-stroke fatigue (PSF) domains within first 6 months after ischemic strokes. There were enrolled in the study 107 patients with acute ischemic strokes. General PSF and certain PSF domains (global, physical, mental, motivational, activity-related) were measured by multidimensional fatigue inventory-20 (MFI-20) scale at hospital stay, in 1, 3 and 6 months after stroke occurrence. Brain MRI studies included cerebral infarct localization, planimetric measurements of infarct volumes, measurement of brain atrophy indexes (bifrontal, bicaudate, cortical atrophy indexes, width of third ventricle) and evaluation of leukoaraiosis severity, according to Fazekas scale. In univariate logistic regression analysis infarcts volumes as well as brain atrophy indexes were not significantly associated with risk of any PSF domain at any time points within first 6 months after ischemic strokes. On the other hand, it had been found reliable associations between subcortical infarcts and increased risk of PSF domains which are related just to physical activity (physical PSF, activity-related PSF) in 1 month after stroke onset and later, as well as reliable associations between infratentorial infarcts and risk of global PSF domain in 3 months after stroke and later. Moreover, it have been revealed significant direct associations between severity of white matter lesions and risk of mental PSF in 3 months after stroke onset and later. Subcortical infarcts may be risk factors for development of physical PSF domain, infratentorial infarcts - risk factors for development of global PSF domain, leukoaraiosis extension - risk factor for development of mental PSF domain but not early than 1 month after stroke occurrence.

Intra-thoracic fat volume is associated with myocardial infarction in patients with metabolic syndrome.

PubMed

Jolly, Umjeet S; Soliman, Abraam; McKenzie, Charles; Peters, Terry; Stirrat, John; Nevis, Immaculate; Brymer, Matthew; Joy, Tisha; Drangova, Maria; White, James A

2013-09-10

Visceral adiposity is increased in those with Metabolic Syndrome (MetS) and atherosclerotic disease burden. In this study we evaluate for associations between intra-thoracic fat volume (ITFV) and myocardial infarction (MI) in patients with MetS. Ninety-four patients with MetS, MI or both were identified from a cardiovascular CMR clinical registry. MetS was defined in accordance to published guidelines; where-as MI was defined as the presence of subendocardial-based injury on late gadolinium enhancement imaging in a coronary vascular distribution. A healthy control group was also obtained from the same registry. Patients were selected into the following groups: MetS+/MI- (N = 32), MetS-/MI + (N = 30), MetS+/MI + (N = 32), MetS-/MI- (N = 16). ITFV quantification was performed using signal threshold analysis of sequential sagittal CMR datasets (HASTE) and indexed to body mass index. The mean age of the population was 59.8 ± 12.5 years. MetS+ patients (N=64) demonstrated a significantly higher indexed ITFV compared to MetS- patients (p = 0.05). Patients in respective MetS-/MI-, MetS+/MI-, MetS-/MI+, and MetS+/MI + study groups demonstrated a progressive elevation in the indexed ITFV (22.3 ± 10.6, 28.6 ± 12.6, 30.6 ± 12.3, and 35.2 ± 1.4 ml/kg/m(2), (p = 0.002)). Among MetS+ patients those with MI showed a significantly higher indexed ITFV compared to those without MI (p = 0.02). ITFV is elevated in patients with MetS and incrementally elevated among those with evidence of prior ischemic myocardial injury. Accordingly, the quantification of ITFV may be a valuable marker of myocardial infarction risk among patients with MetS and warrants further investigation.

Influence of ezetimibe in addition to high-dose atorvastatin therapy on plaque composition in patients with ST-segment elevation myocardial infarction assessed by serial: Intravascular ultrasound with iMap: the OCTIVUS trial.

PubMed

Hougaard, Mikkel; Hansen, Henrik Steen; Thayssen, Per; Antonsen, Lisbeth; Junker, Anders; Veien, Karsten; Jensen, Lisette Okkels

2017-03-01

The aim of this study was to examine the influence of ezetimibe in addition to atorvastatin on plaque composition in patients with first-time ST-segment Elevation Myocardial Infarction treated with primary percutaneous intervention. Eighty-seven patients were randomized (1:1) to ezetimibe 10mg or placebo in addition to Atorvastatin 80mg. Intravascular ultrasound with iMap was performed at baseline and after 12months in a non-infarct-related artery. Primary endpoint was change in necrotic core (NC). Secondary endpoints were total atheroma volume (TAV) and percentage atheroma volume (PAV). NC did not change significantly: ezetimibe group 24.9 (11.9, 51.3) mm 3 to 24.9 (15.3, 54.5) mm 3 , p=0.76, placebo group 29.4 (16.3, 78.5) mm 3 to 32.0 (16.0, 88.7) mm 3 , p=0.30, (p=0.35 between groups). TAV was reduced in the ezetimibe group only: ezetimibe (200.0 (135.6, 311.9) mm 3 to 189.3 (126.4, 269.1) mm 3 , p<0.001) compared to placebo group (218.4 (163.5, 307.9) mm 3 to 212.2 (149.9, 394.8) mm 3 , p=0.07) (p=0.56 between groups). PAV was reduced in the ezetimibe group only (40.1±8.6% to 39.2±9.0%, p=0.036) compared to placebo group (43.3±9.4% to 42.2±10.7%, p=0.07), p=0.91 between groups. Ezetimibe in addition to atorvastatin therapy did not influence NC content, but was associated with regression of coronary atherosclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation.

PubMed

Tu, Hans T H; Campbell, Bruce C V; Christensen, Soren; Desmond, Patricia M; De Silva, Deidre A; Parsons, Mark W; Churilov, Leonid; Lansberg, Maarten G; Mlynash, Michael; Olivot, Jean-Marc; Straka, Matus; Bammer, Roland; Albers, Gregory W; Donnan, Geoffrey A; Davis, Stephen M

2015-06-01

Atrial fibrillation is associated with greater baseline neurological impairment and worse outcomes following ischemic stroke. Previous studies suggest that greater volumes of more severe baseline hypoperfusion in patients with history of atrial fibrillation may explain this association. We further investigated this association by comparing patients with and without atrial fibrillation on initial examination following stroke using pooled multimodal magnetic resonance imaging and clinical data from the Echoplanar Imaging Thrombolytic Evaluation Trial and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. Echoplanar Imaging Thrombolytic Evaluation Trial was a trial of 101 ischemic stroke patients randomized to intravenous tissue plasminogen activator or placebo, and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution was a prospective cohort of 74 ischemic stroke patients treated with intravenous tissue plasminogen activator at three to six hours following symptom onset. Patients underwent multimodal magnetic resonance imaging before treatment, at three to five days and three-months after stroke in Echoplanar Imaging Thrombolytic Evaluation Trial; before treatment, three to six hours after treatment and one-month after stroke in Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution. Patients were assessed with the National Institutes of Health Stroke Scale and the modified Rankin scale before treatment and at three-months after stroke. Patients were categorized into definite atrial fibrillation (present on initial examination), probable atrial fibrillation (history but no atrial fibrillation on initial examination), and no atrial fibrillation. Perfusion data were reprocessed with automated magnetic resonance imaging analysis software (RAPID, Stanford University, Stanford, CA, USA). Hypoperfusion volumes were defined using time to maximum delays in two-second increments from >4 to >8 s. Hemorrhagic transformation was classified according to the European Cooperative Acute Stroke Studies criteria. Of the 175 patients, 28 had definite atrial fibrillation, 30 probable atrial fibrillation, 111 no atrial fibrillation, and six were excluded due to insufficient imaging data. At baseline, patients with definite atrial fibrillation had more severe hypoperfusion (median time to maximum >8 s, volume 48 vs. 29 ml, P = 0.02) compared with patients with no atrial fibrillation. At outcome, patients with definite atrial fibrillation had greater infarct growth (median volume 47 vs. 8 ml, P = 0.001), larger infarcts (median volume 75 vs. 23 ml, P = 0.001), more frequent parenchymal hematoma grade hemorrhagic transformation (30% vs. 10%, P = 0.03), worse functional outcomes (median modified Rankin scale score 4 vs. 3, P = 0.03), and higher mortality (36% vs. 16%, P = 0·.3) compared with patients with no atrial fibrillation. Definite atrial fibrillation was independently associated with increased parenchymal hematoma (odds ratio = 6.05, 95% confidence interval 1.60-22.83) but not poor functional outcome (modified Rankin scale 3-6, odds ratio = 0.99, 95% confidence interval 0.35-2.80) or mortality (odds ratio = 2.54, 95% confidence interval 0.86-7.49) three-months following stroke, after adjusting for other baseline imbalances. Atrial fibrillation is associated with greater volumes of more severe baseline hypoperfusion, leading to higher infarct growth, more frequent severe hemorrhagic transformation and worse stroke outcomes. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Structural MRI Predictors of Late-Life Cognition Differ Across African Americans, Hispanics, and Whites.

PubMed

Zahodne, Laura B; Manly, Jennifer J; Narkhede, Atul; Griffith, Erica Y; DeCarli, Charles; Schupf, Nicole S; Mayeux, Richard; Brickman, Adam M

2015-01-01

Structural magnetic resonance imaging (MRI) provides key biomarkers to predict onset and track progression of Alzheimer's disease (AD). However, most published reports of relationships between MRI variables and cognition in older adults include racially, ethnically, and socioeconomically homogenous samples. Racial/ethnic differences in MRI variables and cognitive performance, as well as health, socioeconomic status and psychological factors, raise the possibility that brain-behavior relationships may be stronger or weaker in different groups. The current study tested whether MRI predictors of cognition differ in African Americans and Hispanics, compared with non-Hispanic Whites. Participants were 638 non-demented older adults (29% non-Hispanic White, 36% African American, 35% Hispanic) in the Washington Heights-Inwood Columbia Aging Project. Composite scores of memory, language, speed/executive functioning, and visuospatial function were derived from a neuropsychological battery. Hippocampal volume, regional cortical thickness, infarcts, and white matter hyperintensity (WMH) volumes were quantified with FreeSurfer and in-house developed procedures. Multiple-group regression analysis, in which each cognitive composite score was regressed onto MRI variables, demographics, and cardiovascular health, tested which paths differed across groups. Larger WMH volume was associated with worse language and speed/executive functioning among African Americans, but not among non-Hispanic Whites. Larger hippocampal volume was more strongly associated with better memory among non-Hispanic Whites compared with Hispanics. Cortical thickness and infarcts were similarly associated with cognition across groups. The main finding of this study was that certain MRI predictors of cognition differed across racial/ethnic groups. These results highlight the critical need for more diverse samples in the study of cognitive aging, as the type and relation of neurobiological substrates of cognitive functioning may be different for different groups.

Action of acetylstrophanthidin on experimental myocardial infarction.

NASA Technical Reports Server (NTRS)

Nola, G. T.; Pope, S. E.; Harrison, D. C.

1972-01-01

An experimental animal model with acute myocardial infarction of a size insufficient to produce profound heart failure or shock was used to study the effects of acute infarction on digitalis tolerance and the hemodynamic changes produced by moderate and large doses of acetylstrophanthidin. With acute myocardial infarction, digitalis toxic arrhythmias could be precipitated with significantly lower doses of digitalis than in animals without myocardial infarction. There was no precise correlation between the size of infarction and the toxic dose of glycoside. Coronary artery ligation produced a stable but relatively depressed circulatory state, as evidenced by lowered cardiac output and stroke volume and elevated systemic vascular resistance and left atrial mean pressure. When digitalis was infused, the following significant changes were observed at nontoxic doses: (1) elevation of aortic and left ventricular pressures; (2) further decline in cardiac output; and (3) decreased left atrial mean pressure.

Inhibition of Cathepsin B Alleviates Secondary Degeneration in Ipsilateral Thalamus After Focal Cerebral Infarction in Adult Rats.

PubMed

Zuo, Xialin; Hou, Qinghua; Jin, Jizi; Zhan, Lixuan; Li, Xinyu; Sun, Weiwen; Lin, Kunqin; Xu, En

2016-09-01

Secondary degeneration in areas beyond ischemic foci can inhibit poststroke recovery. The cysteine protease Cathepsin B (CathB) regulates cell death and intracellular protein catabolism. To investigate the roles of CathB in the development of secondary degeneration in the ventroposterior nucleus (VPN) of the ipsilateral thalamus after focal cerebral infarction, infarct volumes, immunohistochemistry and immunofluorescence, and Western blotting analyses were conducted in a distal middle cerebral artery occlusion (dMCAO) stroke model in adult rats. We observed marked neuron loss and gliosis in the ipsilateral thalamus after dMCAO, and the expression of CathB and cleaved caspase-3 in the VPN was significantly upregulated; glial cells were the major source of CathB. Although it had no effect on infarct volume, delayed intracerebroventricular treatment with the membrane-permeable CathB inhibitor CA-074Me suppressed the expression of CathB and cleaved caspase-3 in ipsilateral VPN and accordingly alleviated the secondary degeneration. These data indicate that CathB mediates a novel mechanism of secondary degeneration in the VPN of the ipsilateral thalamus after focal cortical infarction and suggest that CathB might be a therapeutic target for the prevention of secondary degeneration in patients after stroke. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Computed Tomography-Based Imaging of Voxel-Wise Lesion Water Uptake in Ischemic Brain: Relationship Between Density and Direct Volumetry.

PubMed

Broocks, Gabriel; Flottmann, Fabian; Ernst, Marielle; Faizy, Tobias Djamsched; Minnerup, Jens; Siemonsen, Susanne; Fiehler, Jens; Kemmling, Andre

2018-04-01

Net water uptake per volume of brain tissue may be calculated by computed tomography (CT) density, and this imaging biomarker has recently been investigated as a predictor of lesion age in acute stroke. However, the hypothesis that measurements of CT density may be used to quantify net water uptake per volume of infarct lesion has not been validated by direct volumetric measurements so far. The purpose of this study was to (1) develop a theoretical relationship between CT density reduction and net water uptake per volume of ischemic lesions and (2) confirm this relationship by quantitative in vitro and in vivo CT image analysis using direct volumetric measurements. We developed a theoretical rationale for a linear relationship between net water uptake per volume of ischemic lesions and CT attenuation. The derived relationship between water uptake and CT density was tested in vitro in a set of increasingly diluted iodine solutions with successive CT measurements. Furthermore, the consistency of this relationship was evaluated using human in vivo CT images in a retrospective multicentric cohort. In 50 edematous infarct lesions, net water uptake was determined by direct measurement of the volumetric difference between the ischemic and normal hemisphere and was correlated with net water uptake calculated by ischemic density measurements. With regard to in vitro data, water uptake by density measurement was equivalent to direct volumetric measurement (r = 0.99, P < 0.0001; mean ± SD difference, -0.29% ± 0.39%, not different from 0, P < 0.0001). In the study cohort, the mean ± SD uptake of water within infarct measured by volumetry was 44.7 ± 26.8 mL and the mean percent water uptake per lesion volume was 22.7% ± 7.4%. This was equivalent to percent water uptake obtained from density measurements: 21.4% ± 6.4%. The mean difference between percent water uptake by direct volumetry and percent water uptake by CT density was -1.79% ± 3.40%, which was not significantly different from 0 (P < 0.0001). Volume of water uptake in infarct lesions can be calculated quantitatively by relative CT density measurements. Voxel-wise imaging of water uptake depicts lesion pathophysiology and could serve as a quantitative imaging biomarker of acute infarct lesions.

Relative cerebral blood volume is associated with collateral status and infarct growth in stroke patients in SWIFT PRIME.

PubMed

Arenillas, Juan F; Cortijo, Elisa; García-Bermejo, Pablo; Levy, Elad I; Jahan, Reza; Goyal, Mayank; Saver, Jeffrey L; Albers, Gregory W

2017-01-01

We aimed to evaluate how predefined candidate cerebral perfusion parameters correlate with collateral circulation status and to assess their capacity to predict infarct growth in patients with acute ischemic stroke (AIS) eligible for endovascular therapy. Patients enrolled in the SWIFT PRIME trial with baseline computed tomography perfusion (CTP) scans were included. RAPID software was used to calculate mean relative cerebral blood volume (rCBV) in hypoperfused regions, and hypoperfusion index ratio (HIR). Blind assessments of collaterals were performed using CT angiography in the whole sample and cerebral angiogram in the endovascular group. Reperfusion was assessed on 27-h CTP; infarct volume was assessed on 27-h magnetic resonance imaging/CT scans. Logistic and rank linear regression models were conducted. We included 158 patients. High rCBV ( p = 0.03) and low HIR ( p = 0.03) were associated with good collaterals. A positive association was found between rCBV and better collateral grades on cerebral angiography ( p = 0.01). Baseline and 27-h follow-up CTP were available for 115 patients, of whom 74 (64%) achieved successful reperfusion. Lower rCBV predicted a higher infarct growth in successfully reperfused patients ( p = 0.038) and in the endovascular treatment group ( p = 0.049). Finally, rCBV and HIR may serve as markers of collateral circulation in AIS patients prior to endovascular therapy. Unique identifier: NCT0165746.

Flow dynamics and energy efficiency of flow in the left ventricle during myocardial infarction.

PubMed

Vasudevan, Vivek; Low, Adriel Jia Jun; Annamalai, Sarayu Parimal; Sampath, Smita; Poh, Kian Keong; Totman, Teresa; Mazlan, Muhammad; Croft, Grace; Richards, A Mark; de Kleijn, Dominique P V; Chin, Chih-Liang; Yap, Choon Hwai

2017-10-01

Cardiovascular disease is a leading cause of death worldwide, where myocardial infarction (MI) is a major category. After infarction, the heart has difficulty providing sufficient energy for circulation, and thus, understanding the heart's energy efficiency is important. We induced MI in a porcine animal model via circumflex ligation and acquired multiple-slice cine magnetic resonance (MR) images in a longitudinal manner-before infarction, and 1 week (acute) and 4 weeks (chronic) after infarction. Computational fluid dynamic simulations were performed based on MR images to obtain detailed fluid dynamics and energy dynamics of the left ventricles. Results showed that energy efficiency flow through the heart decreased at the acute time point. Since the heart was observed to experience changes in heart rate, stroke volume and chamber size over the two post-infarction time points, simulations were performed to test the effect of each of the three parameters. Increasing heart rate and stroke volume were found to significantly decrease flow energy efficiency, but the effect of chamber size was inconsistent. Strong complex interplay was observed between the three parameters, necessitating the use of non-dimensional parameterization to characterize flow energy efficiency. The ratio of Reynolds to Strouhal number, which is a form of Womersley number, was found to be the most effective non-dimensional parameter to represent energy efficiency of flow in the heart. We believe that this non-dimensional number can be computed for clinical cases via ultrasound and hypothesize that it can serve as a biomarker for clinical evaluations.

Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction.

PubMed

Liu, Xiaoli; Simpson, Jeremy A; Brunt, Keith R; Ward, Christopher A; Hall, Sean R R; Kinobe, Robert T; Barrette, Valerie; Tse, M Yat; Pang, Stephen C; Pachori, Alok S; Dzau, Victor J; Ogunyankin, Kofo O; Melo, Luis G

2007-07-01

We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long-term survival and prevention of postinfarction heart failure has not been determined. We assessed the effect of HO-1 gene delivery on long-term survival, myocardial function, and left ventricular (LV) remodeling 1 yr after myocardial infarction (MI) using echocardiographic imaging, pressure-volume (PV) analysis, and histomorphometric approaches. Two groups of Lewis rats were injected with 2 x 10(11) particles of AAV-LacZ (control) or AAV-human HO-1 (hHO-1) in the anterior-posterior apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and PV analysis of LV function were obtained at 2 wk and 12 mo after I/R. One year after acute MI, mortality was markedly reduced in the HO-1-treated animals compared with the LacZ-treated animals. PV analysis demonstrated significantly enhanced LV developed pressure, elevated maximal dP/dt, and lower end-diastolic volume in the HO-1 animals compared with the LacZ animals. Echocardiography showed a larger apical anterior-to-posterior wall ratio in HO-1 animals compared with LacZ animals. Morphometric analysis revealed extensive myocardial scarring and fibrosis in the infarcted LV area of LacZ animals, which was reduced by 62% in HO-1 animals. These results suggest that preemptive HO-1 gene delivery may be useful as a therapeutic strategy to reduce post-MI LV remodeling and heart failure.

Impact of timing of cranioplasty on hydrocephalus after decompressive hemicraniectomy in malignant middle cerebral artery infarction.

PubMed

Finger, Tobias; Prinz, Vincent; Schreck, Evelyn; Pinczolits, Alexandra; Bayerl, Simon; Liman, Thomas; Woitzik, Johannes; Vajkoczy, Peter

2017-02-01

Patients with malignant middle cerebral artery infarction frequently develop hydrocephalus after decompressive hemicraniectomy. Hydrocephalus itself and known shunt related complications after ventriculo-peritoneal shunt implantation may negatively impact patientś outcome. Here, we aimed to identify factors associated with the development of hydrocephalus after decompressive hemicraniectomy in malignant middle cerebral artery infarction. A total of 99 consecutive patients with the diagnosis of large hemispheric infarctions and the indication for decompressive hemicraniectomy were included. We retrospectively evaluated patient characteristics (gender, age and selected preoperative risk factors), stroke characteristics (side, stroke volume and existing mass effect) and surgical characteristics (size of the bone flap, initial complication rate, time to cranioplasty, complication rate following cranioplasty, type of implant, number of revision surgeries and mortality). Frequency of hydrocephalus development was 10% in our cohort. Patients who developed a hydrocephalus had an earlier time point of bone flap reimplantation compared to the control group (no hydrocephalus=164±104days, hydrocephalus=108±52days, p<0.05). Additionally, numbers of revision surgeries after cranioplasty was associated with hydrocephalus with a trend towards significance (p=0.08). Communicating hydrocephalus is frequent in patients with malignant middle cerebral artery infarction after decompressive hemicraniectomy. A later time point of cranioplasty might lead to a lower incidence of required shunting procedures in general as we could show in our patient cohort. Copyright © 2016 Elsevier B.V. All rights reserved.

Greater Cincinnati/Northern Kentucky Stroke Study: volume of first-ever ischemic stroke among blacks in a population-based study.

PubMed

Kissela, B; Broderick, J; Woo, D; Kothari, R; Miller, R; Khoury, J; Brott, T; Pancioli, A; Jauch, E; Gebel, J; Shukla, R; Alwell, K; Tomsick, T

2001-06-01

The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm(3). The volume of first-ever ischemic stroke in the population is not known. The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured. There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm(3) (interquartile range, 0.5 to 8.8 cm(3)). There was a significant relation between location of lesion and infarct size (P<0.001) and between volume and mechanism of stroke (P=0.001). The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.

A pilot study on the correlation of tongue manifestation with the site of cerebral infarction in patients with stroke.

PubMed

Liu, Ping; Gao, Li; Song, Jue-Xian; Zhao, Hai-Ping; Wu, Xiao-Guang; Xu, Chang-Min; Huang, Li-Yuan; Wang, Ping-Ping; Luo, Yu-Min

2014-11-01

To discuss the correlation of tongue manifestation with the site of cerebral infarction in patients with acute cerebral infarction. From March 2008 to February 2009, 200 cases of hospitalized patients with first unilateral cerebral infarction were chosen in the Department of Neurology, Xuanwu Hospital. The correlation of different tongue color, fur texture, fur color with the site of cerebral infarction was analyzed. The site of cerebral infarction in patients were compared between different tongue color by Chisquare test (P=0.314), and further correspondence analysis demonstrated that there was correlation between red tongue and cortical-subcortical infarction group. The site of cerebral infarction in patients were compared between thick fur group and thin fur group, cortical-subcortical infarction occurred more frequently in the former (P=0.0008). The site of cerebral infarction in patients were compared between dry fur group, moist fur group and smooth fur group, correspondence analysis demonstrated there was correlation between dry fur and cortical-subcortical group. The site of cerebral infarction in the patients were compared between white fur group, white-yellow fur group and yellow fur group (P=0.010), and correspondence analysis demonstrated there was correlation between white fur and brainstem infarction; white-yellow fur has relationship with cortical infarction; subcortical infarction was weakly related with white-yellow fur; there was closer relationship between yellow fur and cortical-subcortical infarction. The change of tongue manifestation was associated with the site of cerebral infarction in patients, providing a new combining site for diagnosing cerebrovascular diseases by integrative medicine.

MRI Assessment of Uterine Artery Patency and Fibroid Infarction Rates 6 Months after Uterine Artery Embolization with Nonspherical Polyvinyl Alcohol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Raj, E-mail: rajdas@nhs.net; Gonsalves, Michael; Vlahos, Ioannis

Purpose: We have observed significant rates of uterine artery patency after uterine artery embolization (UAE) with nonspherical polyvinyl alcohol (nsPVA) on 6 month follow-up MR scanning. The study aim was to quantitatively assess uterine artery patency after UAE with nsPVA and to assess the effect of continued uterine artery patency on outcomes. Methods: A single centre, retrospective study of 50 patients undergoing bilateral UAE for uterine leiomyomata was undertaken. Pelvic MRI was performed before and 6 months after UAE. All embolizations were performed with nsPVA. Outcome measures included uterine artery patency, uterine and dominant fibroid volume, dominant fibroid percentage infarction,more » presence of ovarian arterial collaterals, and symptom scores assessed by the Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL). Results: Magnetic resonance angiographic evidence of uterine artery recanalization was demonstrated in 90 % of the patients (64 % bilateral, 26 % unilateral) at 6 months. Eighty percent of all dominant fibroids demonstrated >90 % infarction. The mean percentage reduction in dominant fibroid volume was 35 %. No significant difference was identified between nonpatent, unilateral, and bilateral recanalization of the uterine arteries with regard to percentage dominant fibroid infarction or dominant fibroid volume reduction. The presence of bilaterally or unilaterally patent uterine arteries was not associated with inferior clinical outcomes (symptom score or UFS-QOL scores) at 6 months. Conclusion: The high rates of uterine artery patency challenge the current paradigm that nsPVA is a permanent embolic agent and that permanent uterine artery occlusion is necessary to optimally treat uterine fibroids. Despite high rates of uterine artery recanalization in this cohort, satisfactory fibroid infarction rates and UFS-QOL scores were achieved.« less

Cardioprotective Effect of Intermittent Fasting is Associated with an Elevation of Adiponectin Levels in Rats

PubMed Central

Wan, Ruiqian; Ahmet, Ismayil; Brown, Martin; Cheng, Aiwu; Kamimura, Naomi; Talan, Mark; Mattson, Mark P.

2009-01-01

It has been reported that dietary energy restriction, including intermittent fasting (IF), can protect heart and brain cells against injury and improve functional outcome in animal models of myocardial infarction and stroke. Here we report that IF improves glycemic control and protects the myocardium against ischemia-induced cell damage and inflammation in rats. Echocardiographic analysis of heart structural and functional variables revealed that IF attenuates the growth-related increase in posterior ventricular wall thickness, , end systolic and diastolic volumes, and reduces the ejection fraction. The size of the ischemic infarct 24 hours following permanent ligation of a coronary artery was significantly smaller, and markers of inflammation (infiltration of leukocytes in the area at risk and plasma IL-6 levels) were less, in IF rats compared to rats on the control diet. IF resulted in increased levels of circulating adiponectin prior to and after myocardial infarction. Because recent studies have shown that adiponectin can protect the heart against ischemic injury, our findings suggest a potential role for adiponectin as a mediator of the cardioprotective effect of IF. PMID:19423320

Long-term effects of brief hypoxia due to cardiac arrest: Hippocampal reductions and memory deficits.

PubMed

Stamenova, Vess; Nicola, Raneen; Aharon-Peretz, Judith; Goldsher, Dorith; Kapeliovich, Michael; Gilboa, Asaf

2018-05-01

To examine the effects of brief hypoxia (<7 min) due to cardiac arrest on the integrity of the brain and performance on memory and executive functions tasks. Patients after out-of-hospital cardiac arrest (CA) (n = 9), who were deemed neurologically intact on discharge, were compared to matched patients with myocardial infarction (MI) (n = 9). A battery of clinical and experimental memory and executive functions neuropsychological tests were administered and MRI scans for all patients were collected. Measures of subcortical and cortical volumes and cortical thickness were obtained using FreeSurfer. Manual segmentations of the hippocampus were also performed. APACHE-II scores were calculated based on metrics collected at admission to ICCU for all patients. Significant differences between the two groups were observed on several verbal memory tests. Both hippocampi were significantly reduced (p < 0.05) in the CA patients, relative to MI patients. Hippocampal subfields segmentation showed significantly reduced presubiculum volumes bilaterally. CA patients had on average 10% reduction in volumes bilaterally across hippocampal subfields. No cortical thickness differences survived correction. Significant correlations were observed in the CA group only between the hippocampal volumes and performance on verbal memory tasks, including recollection. Hippocampal volumes and several memory measures (but not other cognitive domains) were strongly correlated with APACHE-II scores on admission in the CA group, but not in the MI group CONCLUSIONS: Chronic patients with cardiac arrest who were discharged from hospital in "good neurological condition" showed an average of 10% reduction in hippocampal volume bilaterally and significant verbal memory deficits relative to matched controls with myocardial infarction, suggesting even brief hypoxic periods suffice to lead to specific hippocampal damage. Copyright © 2018 Elsevier B.V. All rights reserved.

Orthogonal design to sift the optimal parameter of Neiguan acupuncture for cerebral infarction

PubMed Central

Zhang, Yanan; Yang, Sha; Fan, Xiaonong; Wang, Shu; He, Nina; Li, Lingxin; Luo, Ding; Shi, Xuemin

2013-01-01

The individual difference and non-repeatability in acupuncture have not only restricted the development of acupuncture, but have also affected the specificity of acupoints. The present study used instruments to control needle depth, lifting and thrusting frequency, and the duration of acupuncture. Effects of the quantified acupuncture were observed at Neiguan (PC6) with different stimulation parameters. A frequency of 1, 2, or 3 Hz and duration of 5, 60, or 180 seconds were used to observe cerebral blood flow and ratio of infarct volume recovery. Results showed that stimulation at Neiguan with a frequency of 1 Hz and long duration of 180 seconds or 2/3 Hz and long duration of 5/60 seconds significantly increased cerebral blood flow and decreased the ratio of infarct volume. Interactions between frequency and duration play a critical role in quantified acupuncture therapy. PMID:25206575

Effect of baculovirus P35 protein on apoptosis in brain tissue of rats with acute cerebral infarction.

PubMed

Ji, J F; Ma, X H

2015-08-10

We explored the effect of baculovirus P35 protein on apoptosis in the brain tissue of rats with acute cerebral infarction (ACI). A rat model of middle cerebral artery infarction was created. The rats were randomly divided into sham, model, and treatment groups. Baculovirus P35 protein was injected into the intracranial arteries of the treatment group rats. The rats in the model group were given an equal volume of phosphate-buffered saline. The rats were sacrificed after 72 h and the brain tissue was separated. The levels of caspase-3, Bcl-2, and Bax mRNA, the brain cell apoptosis index, and the infarct size were determined. After 72 h, the levels of caspase-3 and Bax mRNA in the model and treatment groups were significantly greater than in the sham group, and the levels of Bcl-2 mRNA were significantly smaller (P < 0.05). The levels of caspase-3 and Bax mRNA were significantly lower in the treatment group than in the model group, and the level of Bcl-2 mRNA was significantly greater (P < 0.05). Compared with the sham group, the brain tissue apoptosis index and the cerebral infarction area increased significantly in the model and treatment groups (P < 0.05). The brain tissue apoptosis index and cerebral infarction area in the treatment group were significantly lower than in the model group (P < 0.05). Baculovirus P35 protein can effectively inhibit brain cell apoptosis in rats with ACI. It delayed apoptosis and necrosis in subjects with ACI tissue and had a protective effect on brain tissue.

Dl-3-n-butylphthalide protects the blood brain barrier of cerebral infarction by activating the Nrf-2/HO-1 signaling pathway in mice.

PubMed

Zhao, Y-J; Nai, Y; Ma, Q-S; Song, D-J; Ma, Y-B; Zhang, L-H; Mi, L-X

2018-04-01

The aim of this study was to explore whether Dl-3-n-butylphthalide (DBT) could protect blood-brain barrier (BBB) of mice with experimental cerebral infarction and the relevant mechanism. Adult male CD-1 mice were selected as the study objects. The permanent middle cerebral artery occlusion (MCAO) model was prepared by Longa's modified suture-occluded method. The mice were randomly divided into 3 groups: the sham operation group (Sham group), the cerebral infarction model group (CI group) and the DBT (120 mg/kg) intervention group (DBT group). Neurologic function deficits were evaluated by Longa's modified scoring method after 24 h of permanent MCAO. The wet and dry weight method was used for measuring water content in brain tissues. 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining method was applied to determine the volume of cerebral infarction. Changes in the protein and messenger ribonucleic acid (mRNA) expression levels of matrix metallopeptidase 9 (MMP-9), claudin-5, vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), NF-E2 related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) in ischemic brain tissues were detected using immunohistochemistry, Western blotting and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Ultrastructure changes in BBBs were observed under an electron microscope. DBT improved the neurologic function deficits of mice and reduced the infarction volume of mice with cerebral infarction. DBT alleviated edema and decreased the permeability of BBBs of mice with cerebral infarction. DBT down-regulated the expression of MMP-9 and up-regulated the expression of claudin-5 in brain tissues of mice with cerebral infarction. DBT increased the expressions of VEGF and GFAP. DBT improved the ultrastructure in capillary endothelial cells of BBBs and increased the expressions of Nrf-2 and HO-1. DBT may protect BBB by activating the Nrf-2/HO-1 signaling pathway, thus achieving its protective effect on the brain.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome.

PubMed

Naess, Halvor; Romi, Fredrik

2011-01-01

To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome

PubMed Central

Naess, Halvor; Romi, Fredrik

2011-01-01

Background: To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Methods: Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Results: Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Conclusion: Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis. PMID:21915166

Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: Occurrence and perfusion characteristics

PubMed Central

Sommer, Wieland H; Bollwein, Christine; Thierfelder, Kolja M; Baumann, Alena; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F; Plate, Annika; Straube, Andreas

2015-01-01

We aimed to investigate the overall prevalence and possible factors influencing the occurrence of crossed cerebellar diaschisis after acute middle cerebral artery infarction using whole-brain CT perfusion. A total of 156 patients with unilateral hypoperfusion of the middle cerebral artery territory formed the study cohort; 352 patients without hypoperfusion served as controls. We performed blinded reading of different perfusion maps for the presence of crossed cerebellar diaschisis and determined the relative supratentorial and cerebellar perfusion reduction. Moreover, imaging patterns (location and volume of hypoperfusion) and clinical factors (age, sex, time from symptom onset) resulting in crossed cerebellar diaschisis were analysed. Crossed cerebellar diaschisis was detected in 35.3% of the patients with middle cerebral artery infarction. Crossed cerebellar diaschisis was significantly associated with hypoperfusion involving the left hemisphere, the frontal lobe and the thalamus. The degree of the relative supratentorial perfusion reduction was significantly more pronounced in crossed cerebellar diaschisis-positive patients but did not correlate with the relative cerebellar perfusion reduction. Our data suggest that (i) crossed cerebellar diaschisis is a common feature after middle cerebral artery infarction which can robustly be detected using whole-brain CT perfusion, (ii) its occurrence is influenced by location and degree of the supratentorial perfusion reduction rather than infarct volume (iii) other clinical factors (age, sex and time from symptom onset) did not affect the occurrence of crossed cerebellar diaschisis. PMID:26661242

Protective effects of alkaloid extract from Leonurus heterophyllus on cerebral ischemia reperfusion injury by middle cerebral ischemic injury (MCAO) in rats.

PubMed

Liang, Hao; Liu, Ping; Wang, Yunshan; Song, Shuliang; Ji, Aiguo

2011-07-15

The neuronal damage following cerebral ischemia is a serious risk to stroke patients. The aim of this study was to investigate the neuroprotective effects of alkaloid extract from Leonurus heterophyllus (LHAE) on cerebral ischemic injury. After 24 h of reperfusion following ischemia for 2 h induced by middle cerebral artery occlusion (MCAO), some rats were intraperitoneally administered different doses of LHAE (3.6, 7.2, 14.4 mg/kg, respectively). Neurological examination was measured in all animals. Infarct volume, myeloperoxidase (MPO) activity, levels of nitrate/nitrite metabolite (NO) and apoptosis ratio of nerve fiber in brain were determined. The results showed that LHAE at 7.2 mg/kg or 14.4 mg/kg exerted significantly decreasing neurological deficit scores and reducing the infarct volume on rats with focal cerebral ischemic injury (p<0.05). At those dose, the MPO content were significantly decreased in ischemic brain as compared with model group (p<0.05). LHAE at 14.4 mg/kg significantly decreased the NO level compared with the model group (p<0.05). In addition, LHAE significantly decreased the apoptosis ratio of nerve fiber compared with the model group (p<0.05). This study suggests that LHAE may be used for treatment of ischemic stroke as a neuroprotective agent. Further studies are warranted to assess the efficacy and safety of LHAE in patients. Copyright © 2011 Elsevier GmbH. All rights reserved.

Long-term exposure to fine particulate matter, residential proximity to major roads and measures of brain structure.

PubMed

Wilker, Elissa H; Preis, Sarah R; Beiser, Alexa S; Wolf, Philip A; Au, Rhoda; Kloog, Itai; Li, Wenyuan; Schwartz, Joel; Koutrakis, Petros; DeCarli, Charles; Seshadri, Sudha; Mittleman, Murray A

2015-05-01

Long-term exposure to ambient air pollution is associated with cerebrovascular disease and cognitive impairment, but whether it is related to structural changes in the brain is not clear. We examined the associations between residential long-term exposure to ambient air pollution and markers of brain aging using magnetic resonance imaging. Framingham Offspring Study participants who attended the seventh examination were at least 60 years old and free of dementia and stroke were included. We evaluated associations between exposures (fine particulate matter [PM2.5] and residential proximity to major roadways) and measures of total cerebral brain volume, hippocampal volume, white matter hyperintensity volume (log-transformed and extensive white matter hyperintensity volume for age), and covert brain infarcts. Models were adjusted for age, clinical covariates, indicators of socioeconomic position, and temporal trends. A 2-μg/m(3) increase in PM2.5 was associated with -0.32% (95% confidence interval, -0.59 to -0.05) smaller total cerebral brain volume and 1.46 (95% confidence interval, 1.10 to 1.94) higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 (95% confidence interval, 0.01 to 0.19) greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter. Exposure to elevated levels of PM2.5 was associated with smaller total cerebral brain volume, a marker of age-associated brain atrophy, and with higher odds of covert brain infarcts. These findings suggest that air pollution is associated with insidious effects on structural brain aging even in dementia- and stroke-free persons. © 2015 American Heart Association, Inc.

Residual Myocardial Iron Following Intramyocardial Hemorrhage During the Convalescent Phase of Reperfused ST-Segment-Elevation Myocardial Infarction and Adverse Left Ventricular Remodeling.

PubMed

Bulluck, Heerajnarain; Rosmini, Stefania; Abdel-Gadir, Amna; White, Steven K; Bhuva, Anish N; Treibel, Thomas A; Fontana, Marianna; Ramlall, Manish; Hamarneh, Ashraf; Sirker, Alex; Herrey, Anna S; Manisty, Charlotte; Yellon, Derek M; Kellman, Peter; Moon, James C; Hausenloy, Derek J

2016-10-01

The presence of intramyocardial hemorrhage (IMH) in ST-segment-elevation myocardial infarction patients reperfused by primary percutaneous coronary intervention has been associated with residual myocardial iron at follow-up, and its impact on adverse left ventricular (LV) remodeling is incompletely understood and is investigated here. Forty-eight ST-segment-elevation myocardial infarction patients underwent cardiovascular magnetic resonance at 4±2 days post primary percutaneous coronary intervention, of whom 40 had a follow-up scan at 5±2 months. Native T1, T2, and T2* maps were acquired. Eight out of 40 (20%) patients developed adverse LV remodeling. A subset of 28 patients had matching T2* maps, of which 15/28 patients (54%) had IMH. Eighteen of 28 (64%) patients had microvascular obstruction on the acute scan, of whom 15/18 (83%) patients had microvascular obstruction with IMH. On the follow-up scan, 13/15 patients (87%) had evidence of residual iron within the infarct zone. Patients with residual iron had higher T2 in the infarct zone surrounding the residual iron when compared with those without. In patients with adverse LV remodeling, T2 in the infarct zone surrounding the residual iron was also higher than in those without (60 [54-64] ms versus 53 [51-56] ms; P=0.025). Acute myocardial infarct size, extent of microvascular obstruction, and IMH correlated with the change in LV end-diastolic volume (Pearson's rho of 0.64, 0.59, and 0.66, respectively; P=0.18 and 0.62, respectively, for correlation coefficient comparison) and performed equally well on receiver operating characteristic curve for predicting adverse LV remodeling (area under the curve: 0.99, 0.94, and 0.95, respectively; P=0.19 for receiver operating characteristic curve comparison). The majority of ST-segment-elevation myocardial infarction patients with IMH had residual myocardial iron at follow-up. This was associated with persistently elevated T2 values in the surrounding infarct tissue and adverse LV remodeling. IMH and residual myocardial iron may be potential therapeutic targets for preventing adverse LV remodeling in reperfused ST-segment-elevation myocardial infarction patients. © 2016 The Authors.

Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the General Population: The AGES-Reykjavik Study (Age Gene/Environment Susceptibility-Reykjavik Study).

PubMed

Sigurdsson, Sigurdur; Aspelund, Thor; Kjartansson, Olafur; Gudmundsson, Elias F; Jonsdottir, Maria K; Eiriksdottir, Gudny; Jonsson, Palmi V; van Buchem, Mark A; Gudnason, Vilmundur; Launer, Lenore J

2017-09-01

The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from longitudinal population studies is scarce. We investigated the incidence of infarcts in cortical, subcortical, cerebellar, and overall brain regions and how prevalent and incident infarcts associate with cognitive change and incident dementia. Participants (n=2612, 41% men, mean age 74.6±4.8) underwent brain magnetic resonance imaging for the assessment of infarcts and cognitive testing at baseline and on average 5.2 years later. Incident dementia was assessed according to the international guidelines. Twenty-one percent of the study participants developed new infarcts. The risk of incident infarcts in men was higher than the risk in women (1.8; 95% confidence interval, 1.5-2.3). Persons with both incident and prevalent infarcts showed steeper cognitive decline and had almost double relative risk of incident dementia (1.7; 95% confidence interval, 1.3-2.2) compared with those without infarcts. Persons with new subcortical infarcts had the highest risk of incident dementia compared with those without infarcts (2.6; 95% confidence interval, 1.9-3.4). Men are at greater risk of developing incident brain infarcts than women. Persons with incident brain infarcts decline faster in cognition and have an increased risk of dementia compared with those free of infarcts. Incident subcortical infarcts contribute more than cortical and cerebellar infarcts to incident dementia which may indicate that infarcts of small vessel disease origin contribute more to the development of dementia than infarcts of embolic origin in larger vessels. © 2017 American Heart Association, Inc.

Ventilatory Patterning in a Mouse Model of Stroke

PubMed Central

Koo, Brian B; Strohl, Kingman P; Gillombardo, Carl B; Jacono, Frank J

2010-01-01

Cheyne-Stokes respiration (CSR) is a breathing pattern characterized by waxing and waning of breath volume and frequency, and is often recognized following stroke, when causal pathways are often obscure. We used an animal model to address the hypothesis that cerebral infarction is a mechanism for producing breathing instability. Fourteen male A/J mice underwent either stroke (n=7) or sham (n=7) procedure. Ventilation was measured using whole body plethysmography. Respiratory rate (RR), tidal volume (VT) and minute ventilation (Ve) mean values and coefficient of variation were computed for ventilation and oscillatory behavior. In addition, the ventilatory data were computationally fit to models to quantify autocorrelation, mutual information, sample entropy and a nonlinear complexity index. At the same time post procedure, stroke when compared to sham animal breathing consisted of a lower RR and autocorrelation, higher coefficient of variation for VT and higher coefficient of variation for Ve. Mutual information and the nonlinear complexity index were higher in breathing following stroke which also demonstrated a waxing/waning pattern. The absence of stroke in the sham animals was verified anatomically. We conclude that ventilatory pattern following cerebral infarction demonstrated increased variability with increased nonlinear patterning and a waxing/waning pattern, consistent with CSR. PMID:20472101

Sex differences in ischemic stroke sensitivity are influenced by gonadal hormones, not by sex chromosome complement.

PubMed

Manwani, Bharti; Bentivegna, Kathryn; Benashski, Sharon E; Venna, Venugopal Reddy; Xu, Yan; Arnold, Arthur P; McCullough, Louise D

2015-02-01

Epidemiologic studies have shown sex differences in ischemic stroke. The four core genotype (FCG) mouse model, in which the testes determining gene, Sry, has been moved from Y chromosome to an autosome, was used to dissociate the effects of sex hormones from sex chromosome in ischemic stroke outcome. Middle cerebral artery occlusion (MCAO) in gonad intact FCG mice revealed that gonadal males (XXM and XYM) had significantly higher infarct volumes as compared with gonadal females (XXF and XYF). Serum testosterone levels were equivalent in adult XXM and XYM, as was serum estrogen in XXF and XYF mice. To remove the effects of gonadal hormones, gonadectomized FCG mice were subjected to MCAO. Gonadectomy significantly increased infarct volumes in females, while no change was seen in gonadectomized males, indicating that estrogen loss increases ischemic sensitivity. Estradiol supplementation in gonadectomized FCG mice rescued this phenotype. Interestingly, FCG male mice were less sensitive to effects of hormones. This may be due to enhanced expression of the transgene Sry in brains of FCG male mice. Sex differences in ischemic stroke sensitivity appear to be shaped by organizational and activational effects of sex hormones, rather than sex chromosomal complement.

Research of Sleep Disorders in Patients with Acute Cerebral Infarction.

PubMed

Chen, Xiaofang; Bi, Hongye; Zhang, Meiyun; Liu, Haiyan; Wang, Xueying; Zu, Ruonan

2015-11-01

The purpose of this study is to investigate the incidence of sleep disorders (SD), characteristic of cerebral infarction patients with different parts affected. The research selected 101 patients with a first occurrence of acute cerebral infarction as the experimental group, and 86 patients without cerebral infarction as controls. Polysomnography, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and US National Stroke Scale were assessed. Compared with control group, the incidence of SD was higher in experimental group (P < .05), and the incidence of SD in women was more frequent in experimental group (P < .05). There was no significant difference in the types of SD patients with acute cerebral infarction. In addition, the sleep quality of cerebral infarction patients with different parts affected was different: the sleep quality of left hemisphere infarction patients was poor compared with the right one, and the sleep quality of anterior circulation patients was poor compared with posterior circulation patients. Patients with thalamus infarction had a longer sleep time and a shorter sleep latency and stage 2 of non-rapid eye movement sleep compared with non-thalamus infarction group. The prevalence of SD was relatively high in acute cerebral infarction patients, and the detailed classification of acute cerebral infarction may provide a more effective therapeutic method and therefore relieve patients' pain and supply a better quality of sleep. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Absence of accelerated atherosclerotic disease progression after intracoronary infusion of bone marrow derived mononuclear cells in patients with acute myocardial infarction--angiographic and intravascular ultrasound--results from the TErapia Celular Aplicada al Miocardio Pilot study.

PubMed

Arnold, Roman; Villa, Adolfo; Gutiérrez, Hipólito; Sánchez, Pedro L; Gimeno, Federico; Fernández, Maria E; Gutiérrez, Oliver; Mota, Pedro; Sánchez, Ana; García-Frade, Javier; Fernández-Avilés, Francisco; San Román, Jose A

2010-06-01

We tried to evaluate a putative negative effect on coronary atherosclerosis in patients receiving intracoronary infusion of unfractionated bone marrow mononuclear cells (BMMC) following an acute ST-elevation myocardial infarction. Peripheral blood mononuclear cells or enriched CD133(+) BMMC have been associated with accelerated atherosclerosis of the distal segment of the infarct related artery (IRA). Thirty-seven patients with ST-elevation myocardial infarction from the TECAM pilot study underwent intracoronary infusion of autologous BMMC 9 +/- 3.1 days after onset of symptoms. We compared angiographic changes from baseline to 9 months of follow-up in the distal non-stented segment of the IRA, as well as in the contralateral coronary artery, with a matched control group. A subgroup of 15 treated patients underwent additional IVUS within the distal segment of the IRA. No difference between stem cell and control group were found regarding changes in minimum lumen diameter (0.006 +/- 0.42 vs 0.06 +/- 0.41 mm, P = ns) and the percentage of stenosis (-2.68 +/- 12.33% vs -1.78 +/- 8.75%, P = ns) at follow-up. Likewise, no differences were seen regarding changes in the contralateral artery (minimum lumen diameter -0.004 +/- 0.54 mm vs -0.06 +/- 0.35 mm, P = ns). In the intravascular ultrasound substudy, no changes were demonstrated comparing baseline versus follow-up in maximum area stenosis and plaque volume. In this pilot study, analysis of a subgroup of patients found that intracoronary injection of unfractionated BMMC in patients with acute ST-elevation myocardial infarction was not associated with accelerated atherosclerosis progression at mid term. Prospective, randomised studies in large cohorts with long-term angiographic and intravascular ultrasound follow-up are necessary to determine the safety of this therapy. Copyright 2010 Mosby, Inc. All rights reserved.

Migraine with aura and risk of silent brain infarcts and white matter hyperintensities: an MRI study

PubMed Central

Garde, Ellen; Blaabjerg, Morten; Nielsen, Helle H.; Krøigård, Thomas; Østergaard, Kamilla; Møller, Harald S.; Hjelmborg, Jacob; Madsen, Camilla G.; Iversen, Pernille; Kyvik, Kirsten O.; Siebner, Hartwig R.; Ashina, Messoud

2016-01-01

Abstract A small number of population-based studies reported an association between migraine with aura and risk of silent brain infarcts and white matter hyperintensities in females. We investigated these relations in a population-based sample of female twins. We contacted female twins ages 30–60 years identified through the population-based Danish Twin Registry. Based on questionnaire responses, twins were invited to participate in a telephone-based interview conducted by physicians. Headache diagnoses were established according to the International Headache Society criteria. Cases with migraine with aura, their co-twins, and unrelated migraine-free twins (controls) were invited to a brain magnetic resonance imaging scan performed at a single centre. Brain scans were assessed for the presence of infarcts, and white matter hyperintensities (visual rating scales and volumetric analyses) blinded to headache diagnoses. Comparisons were based on 172 cases, 34 co-twins, and 139 control subjects. Compared with control subjects, cases did not differ with regard to frequency of silent brain infarcts (four cases versus one control), periventricular white matter hyperintensity scores [adjusted mean difference (95% confidence interval): −0.1 (−0.5 to 0.2)] or deep white matter hyperintensity scores [adjusted mean difference (95% confidence interval): 0.1 (−0.8 to 1.1)] assessed by Scheltens’ scale. Cases had a slightly higher total white matter hyperintensity volume compared with controls [adjusted mean difference (95% confidence interval): 0.17 (−0.08 to 0.41) cm 3 ] and a similar difference was present in analyses restricted to twin pairs discordant for migraine with aura [adjusted mean difference 0.21 (−0.20 to 0.63)], but these differences did not reach statistical significance. We found no evidence of an association between silent brain infarcts, white matter hyperintensities, and migraine with aura. PMID:27190013

Epicardial infarct repair with bioinductive extracellular matrix promotes vasculogenesis and myocardial recovery.

PubMed

Mewhort, Holly E M; Turnbull, Jeannine D; Satriano, Alessandro; Chow, Kelvin; Flewitt, Jacqueline A; Andrei, Adin-Cristian; Guzzardi, David G; Svystonyuk, Daniyil A; White, James A; Fedak, Paul W M

2016-05-01

Infarcted myocardium can remodel after successful reperfusion, resulting in left ventricular dilation and heart failure. Epicardial infarct repair (EIR) using a bioinductive extracellular matrix (ECM) biomaterial is a novel surgical approach to promote endogenous myocardial repair and functional recovery after myocardial infarction. Using a pre-clinical porcine model of coronary ischemia-reperfusion, we assessed the effects of EIR on regional functional recovery, safety, and possible mechanisms of benefit. An ECM biomaterial (CorMatrix ECM) was applied to the epicardium after 75 minutes of coronary ischemia in a porcine model. Following ischemia-reperfusion injury, animals were randomly assigned in 2:1 fashion to EIR (n = 8) or sham treatment (n = 4). Serial cardiac magnetic resonance imaging was performed on normal (n = 4) and study animals at baseline (1 week) and 6 weeks after treatment. Myocardial function and tissue characteristics were assessed. Functional myocardial recovery was significantly increased by EIR compared with sham treatment (change in regional myocardial contraction at 6 weeks, 28.6 ± 14.0% vs 4.2 ± 13.5% wall thickening, p < 0.05). Animals receiving EIR had reduced adhesions compared with animals receiving sham treatment (1.44 ± 0.51 vs 3.08 ± 0.89, p < 0.05). Myocardial fibrosis was not increased, and EIR did not cause myocardial constriction, as left ventricular compliance by passive pressure distention at matched volumes was similar between groups (13.9 ± 4.0 mm Hg in EIR group vs 16.0 ± 5.2 mm Hg in sham group, p = 0.61). Animals receiving EIR showed evidence of vasculogenesis in the region of functional recovery. In addition to the beneficial effects of successful reperfusion, EIR using a bioinductive ECM enhances myocardial repair and functional recovery. Clinical translation of EIR early after myocardial infarction as an adjunct to surgical revascularization may be warranted in the future. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Overexpression of Human S100B Exacerbates Brain Damage and Periinfarct Gliosis After Permanent Focal Ischemia

PubMed Central

Mori, Takashi; Tan, Jun; Arendash, Gary W.; Koyama, Naoki; Nojima, Yoshiko; Town, Terrence

2009-01-01

Background and Purpose We have previously demonstrated that augmented and prolonged activation of astrocytes detrimentally influences both the subacute and chronic phases of cerebral ischemia. Furthermore, we have suggested that the astrocyte-derived protein S100B may be important in these pathogenic events. However, the causal relationship between S100B and exacerbation of brain damage in vivo remains to be elucidated. Methods Using transgenic mice overexpressing human S100B (Tg huS100B mice), we examined whether S100B plays a cardinal role in aggravation of brain damage after permanent middle cerebral artery occlusion (pMCAO). Results Tg huS100B mice had significantly larger infarct volumes and worse neurological deficits at any time point examined after pMCAO as compared with CD-1 background strain-matched control mice. Infarct volumes in Tg huS100B mice were significantly increased from 1 to 3 and 5 days after pMCAO (delayed infarct expansion), whereas those in control mice were not significantly altered. S100, glial fibrillary acidic protein, and Iba1 burdens in the periinfarct area were significantly increased through to 7 days after pMCAO in Tg huS100B mice, whereas those in control mice reached a plateau at 3 days after pMCAO. Conclusions These results provide genetic evidence that overexpression of human S100B acts to exacerbate brain damage and periinfarct reactive gliosis (astrocytosis and microgliosis) during the subacute phase of pMCAO. PMID:18451356

Down-regulated Na+/K+-ATPase activity in ischemic penumbra after focal cerebral ischemia/reperfusion in rats

PubMed Central

Huang, Hao; Chen, Yang-Mei; Zhu, Fei; Tang, Shi-Ting; Xiao, Ji-Dong; Li, Lv-Li; Lin, Xin-Jing

2015-01-01

This study was aimed to examine whether the Na+/K+ adenosine triphosphatase (Na+/K+-ATPase) activity in ischemic penumbra is associated with the pathogenesis of ischemia/reperfusion-induced brain injury. An experimental model of cerebral ischemia/reperfusion was made by transient middle cerebral artery occlusion (tMCAO) in rats and the changes of Na+/K+-ATPase activity in the ischemic penumbra was examined by Enzyme Assay Kit. Extensive infarction was observed in the frontal and parietal cortical and subcortical areas at 6 h, 24 h, 48 h, 3 d and 7 d after tMCAO. Enzyme Assay analyses revealed the activity of Na+/K+-ATPase was decreased in the ischemic penumbra of model rats after focal cerebral ischemia/reperfusion compared with sham-operated rats, and reduced to its minimum at 48 h, while the infarct volume was enlarged gradually. In addition, accompanied by increased brain water content, apoptosis-related bcl-2 and Bax proteins, apoptotic index and neurologic deficits Longa scores, but fluctuated the ratio of bcl-2/Bax. Correlation analysis showed that the infarct volume, apoptotic index, neurologic deficits Longa scores and brain water content were negatively related with Na+/K+-ATPase activity, while the ratio of bcl-2/Bax was positively related with Na+/K+-ATPase activity. Our results suggest that down-regulated Na+/K+-ATPase activity in ischemic penumbra might be involved in the pathogenesis of cerebral ischemia/reperfusion injury presumably through the imbalance ratio of bcl-2/Bax and neuronal apoptosis, and identify novel target for neuroprotective therapeutic intervention in cerebral ischemic disease. PMID:26722460

Effects on infarct size and left ventricular function of early intravenous injection of anistreplase in acute myocardial infarction. The APSIM Study Investigators.

PubMed

Bassand, J P; Bernard, Y; Lusson, J R; Machecourt, J; Cassagnes, J; Borel, E

1990-03-01

A total of 231 patients suffering from a first acute myocardial infarction were randomly allocated within 4 hours following the onset of symptoms either to anistreplase or anisoylated plasminogen streptokinase activator complex (APSAC), 30 U over 5 minutes, or to conventional heparin therapy, 5000 IU in bolus injection. Heparin was reintroduced in both groups 4 h after initial therapy at a dosage of 500 IU/kg per day. A total of 112 patients received anistreplase and 119 received heparin within a mean period of 188 +/- 62 min following the onset of symptoms. Infarct size was estimated from single photon emission computerized tomography and expressed in percentage of the total myocardial volume. The patency rate of the infarct-related artery was 77% in the anistreplase group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the anistreplase group than in the heparin group (6 absolute percentage point difference). A significant 31% reduction in infarct size was found in the anistreplase group (33% for the anterior wall infarction subgroup [p less than 0.05] and 16% for the inferior wall infarction subgroup, NS). A close inverse relation was found between the values of left ventricular ejection fraction and infarct size (r = -.73, p less than 0.01). In conclusion, early infusion of anistreplase in acute myocardial infarction produced a high early patency rate, a significant limitation of infarct size, and a significant preservation of left ventricular systolic function, mainly in the anterior wall infarctions.

Thyroid-stimulating hormone and adverse left ventricular remodeling following ST-segment elevation myocardial infarction.

PubMed

Reindl, Martin; Feistritzer, Hans-Josef; Reinstadler, Sebastian Johannes; Mueller, Lukas; Tiller, Christina; Brenner, Christoph; Mayr, Agnes; Henninger, Benjamin; Mair, Johannes; Klug, Gert; Metzler, Bernhard

2018-04-01

Adverse left ventricular remodeling is one of the major determinants of heart failure and mortality in patients surviving ST-segment elevation myocardial infarction (STEMI). The hypothalamic-pituitary-thyroid axis is a key cardiovascular regulator; however, the relationship between hypothalamic-pituitary-thyroid status and post-STEMI left ventricular remodeling is unclear. We aimed to investigate the association between thyroid-stimulating hormone concentrations and the development of left ventricular remodeling following reperfused STEMI. In this prospective observational study of 102 consecutive STEMI patients, thyroid-stimulating hormone levels were measured at the first day after infarction and 4 months thereafter. Cardiac magnetic resonance scans were performed within the first week as well as at 4 months follow-up to determine infarct characteristics, myocardial function and as primary endpoint left ventricular remodeling, defined as a 20% or greater increase in left ventricular end-diastolic volume. Patients with left ventricular remodeling ( n=15, 15%) showed significantly lower concentrations of baseline (1.20 [0.92-1.91] vs. 1.73 [1.30-2.60] mU/l; P=0.02) and follow-up (1.11 [0.86-1.28] vs. 1.51 [1.15-2.02] mU/l; P=0.002) thyroid-stimulating hormone. The association between baseline thyroid-stimulating hormone and left ventricular remodeling remained significant after adjustment for major clinical (peak high-sensitivity cardiac troponin T and C-reactive protein, heart rate; odds ratio (OR) 5.33, 95% confidence interval (CI) 1.52-18.63; P=0.01) and cardiac magnetic resonance predictors of left ventricular remodeling (infarct size, microvascular obstruction, ejection fraction; OR 4.59, 95% CI 1.36-15.55; P=0.01). Furthermore, chronic thyroid-stimulating hormone was related to left ventricular remodeling independently of chronic left ventricular remodeling correlates (infarct size, ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume; OR 9.22, 95% CI 1.69-50.22; P=0.01). Baseline and chronic thyroid-stimulating hormone concentrations following STEMI were independently associated with left ventricular remodeling, proposing a novel pathophysiological axis in the development of post-STEMI left ventricular remodeling.

Tissue Sodium Concentration in Myocardial Infarction in Humans: A Quantitative 23Na MR Imaging Study1

PubMed Central

Ouwerkerk, Ronald; Bottomley, Paul A.; Solaiyappan, Meiyappan; Spooner, Amy E.; Tomaselli, Gordon F.; Wu, Katherine C.; Weiss, Robert G.

2008-01-01

Purpose: To prospectively determine whether the absolute tissue sodium concentration (TSC) increases in myocardial infarctions (MIs) in humans and whether TSC is related to infarct size, infarct age, ventricular dysfunction, and/or electrophysiologic inducibility of ventricular arrhythmias. Materials and Methods: Delayed contrast material–enhanced 1.5-T hydrogen 1 (1H) magnetic resonance (MR) imaging was used to measure the size and location of nonacute MIs in 20 patients (18 men, two women; mean age, 63 years ± 9 [standard deviation]; age range, 48–82 years) examined at least 90 days after MI. End-systolic and end-diastolic volumes, ejection fraction, and left ventricle (LV) mass were measured with cine MR imaging. The TSC in normal, infarcted, and adjacent myocardial tissue was measured on sodium 23 (23Na) MR images coregistered with delayed contrast-enhanced 1H MR images. Programmed electric stimulation to induce monomorphic ventricular tachycardia (MVT) was used to assess arrhythmic potential, and myocardial TSC was compared between the inducible MVT and noninducible MVT patient groups. Results: The mean TSC for MIs (59 μmol/g wet weight ± 10) was 30% higher than that for noninfarcted (remote) LV regions (45 μmol/g wet weight ± 5, P < .001) and that for healthy control subjects, and TSC did not correlate with infarct age or functional and morphologic indices. The mean TSC for tissue adjacent to the MI (50 μmol/g wet weight ± 6) was intermediate between that for the MI and that for remote regions. The elevated TSC measured in the MI at 23Na MR imaging lacked sufficient contrast and spatial resolution for routine visualization of MI. Cardiac TSC did not enable differentiation between patients in whom MVT was inducible and those in whom it was not. Conclusion: Absolute TSC is measurable with 23Na MR imaging and is significantly elevated in human MI; however, TSC increase is not related to infarct age, infarct size, or global ventricular function. In regions adjacent to the MI, TSC is slightly increased but not to levels in the MI. © RSNA, 2008 PMID:18566171

ERic Acute StrokE Recanalization: A study using predictive analytics to assess a new device for mechanical thrombectomy.

PubMed

Siemonsen, Susanne; Forkert, Nils D; Bernhardt, Martina; Thomalla, Götz; Bendszus, Martin; Fiehler, Jens

2017-08-01

Aim and hypothesis Using a new study design, we investigate whether next-generation mechanical thrombectomy devices improve clinical outcomes in ischemic stroke patients. We hypothesize that this new methodology is superior to intravenous tissue plasminogen activator therapy alone. Methods and design ERic Acute StrokE Recanalization is an investigator-initiated prospective single-arm, multicenter, controlled, open label study to compare the safety and effectiveness of a new recanalization device and distal access catheter in acute ischemic stroke patients with symptoms attributable to acute ischemic stroke and vessel occlusion of the internal cerebral artery or middle cerebral artery. Study outcome The primary effectiveness endpoint is the volume of saved tissue. Volume of saved tissue is defined as difference of the actual infarct volume and the brain volume that is predicted to develop infarction by using an optimized high-level machine learning model that is trained on data from a historical cohort treated with IV tissue plasminogen activator. Sample size estimates Based on own preliminary data, 45 patients fulfilling all inclusion criteria need to complete the study to show an efficacy >38% with a power of 80% and a one-sided alpha error risk of 0.05 (based on a one sample t-test). Discussion ERic Acute StrokE Recanalization is the first prospective study in interventional stroke therapy to use predictive analytics as primary and secondary endpoint. Such trial design cannot replace randomized controlled trials with clinical endpoints. However, ERic Acute StrokE Recanalization could serve as an exemplary trial design for evaluating nonpivotal neurovascular interventions.

The effect of brain atrophy on outcome after a large cerebral infarction.

PubMed

Lee, Sang Hyung; Oh, Chang Wan; Han, Jung Ho; Kim, Chae-Yong; Kwon, O-Ki; Son, Young-Je; Bae, Hee-Joon; Han, Moon-Ku; Chung, Young Seob

2010-12-01

We retrospectively evaluated the effect of brain atrophy on the outcome of patients after a large cerebral infarct. Between June 2003 and Oct 2008, 134 of 2975 patients with stroke were diagnosed as having a large cerebral infarct. The mean age of the patients was 70 (21-95) y. The mean infarct volume was 223.6±95.2 cm(3) (46.0-491.0). The inter-caudate distance (ICD) was calculated as an indicator of brain atrophy by measuring the hemi-ICD of the intact side and then multiplying by two to account for brain swelling at the infarct site. The mean ICD was 18.0±4.8 mm (9.6-37.6). Forty-nine (36.6%) patients experienced a malignant clinical outcome (MCO) during management in the hospital. Thirty-one (23.1%) patients had a favourable functional outcome (FO) (modified Rankin scale (mRS) ≤3) and 49 (36.6%) had an acceptable functional outcome (AO) (mRS≤4) at 6 months after stroke onset. In the multivariate analysis, brain atrophy (ICD≥20 mm) had a significant and independent protective effect on MCO (p=0.003; OR=0.137; 95% CI 0.037 to 0.503). With respect to FO, the age and infarct volume reached statistical significance (p<0.001, OR=0.844, 95% CI 0.781 to 0.913; p=0.006, OR=0.987, 95% CI 0.977 to 0.996, respectively). Brain atrophy (ICD≥20 mm) was negatively associated only with AO (p=0.022; OR=0.164; 95% CI 0.035 to 0.767). Brain atrophy may have an association with clinical outcome after a large stroke by a trend of saving patients from an MCO but also by interfering with their functional recovery.

Neuroprotective effect of cathodal transcranial direct current stimulation in a rat stroke model.

PubMed

Notturno, Francesca; Pace, Marta; Zappasodi, Filippo; Cam, Etrugul; Bassetti, Claudio L; Uncini, Antonino

2014-07-15

Experimental focal brain ischemia generates in the penumbra recurrent depolarizations which spread across the injured cortex inducing infarct growth. Transcranial direct current stimulation can induce a lasting, polarity-specific, modulation of cortical excitability. To verify whether cathodal transcranial direct current stimulation could reduce the infarct size and the number of depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion technique. In the first experiment 12 ischemic rats received cathodal stimulation (alternating 15 min on and 15 min off) starting 45 min after middle cerebral artery occlusion and lasting 4 h. In the second experiment 12 ischemic rats received cathodal transcranial direct current stimulation with the same protocol but starting soon after middle cerebral artery occlusion and lasting 6 h. In both experiments controls were 12 ischemic rats not receiving stimulation. Cathodal stimulation reduced the infarct volume in the first experiment by 20% (p=0.002) and in the second by 30% (p=0.003). The area of cerebral infarction was smaller in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal stimulation reduced the number of depolarizations (p=0.023) and infarct volume correlated with the number of depolarizations (p=0.048). Our findings indicate that cathodal transcranial direct current stimulation exert a neuroprotective effect in the acute phase of stroke possibly decreasing the number of spreading depolarizations. These findings may have translational relevance and open a new avenue in neuroprotection of stroke in humans. Copyright © 2014. Published by Elsevier B.V.

Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: Occurrence and perfusion characteristics.

PubMed

Sommer, Wieland H; Bollwein, Christine; Thierfelder, Kolja M; Baumann, Alena; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F; Plate, Annika; Straube, Andreas; von Baumgarten, Louisa

2016-04-01

We aimed to investigate the overall prevalence and possible factors influencing the occurrence of crossed cerebellar diaschisis after acute middle cerebral artery infarction using whole-brain CT perfusion. A total of 156 patients with unilateral hypoperfusion of the middle cerebral artery territory formed the study cohort; 352 patients without hypoperfusion served as controls. We performed blinded reading of different perfusion maps for the presence of crossed cerebellar diaschisis and determined the relative supratentorial and cerebellar perfusion reduction. Moreover, imaging patterns (location and volume of hypoperfusion) and clinical factors (age, sex, time from symptom onset) resulting in crossed cerebellar diaschisis were analysed. Crossed cerebellar diaschisis was detected in 35.3% of the patients with middle cerebral artery infarction. Crossed cerebellar diaschisis was significantly associated with hypoperfusion involving the left hemisphere, the frontal lobe and the thalamus. The degree of the relative supratentorial perfusion reduction was significantly more pronounced in crossed cerebellar diaschisis-positive patients but did not correlate with the relative cerebellar perfusion reduction. Our data suggest that (i) crossed cerebellar diaschisis is a common feature after middle cerebral artery infarction which can robustly be detected using whole-brain CT perfusion, (ii) its occurrence is influenced by location and degree of the supratentorial perfusion reduction rather than infarct volume (iii) other clinical factors (age, sex and time from symptom onset) did not affect the occurrence of crossed cerebellar diaschisis. © The Author(s) 2015.

Developments in mechanical thrombectomy devices for the treatment of acute ischemic stroke.

PubMed

Mordasini, Pasquale; Gralla, Jan

2016-01-01

Several recent prospective randomized controlled trials of endovascular stroke therapy using latest generation thrombectomy devices, so called stent-retrievers, have shown significantly improved clinical outcome compared to the standard treatment with intra-venous thrombolysis using r-tPA alone. Despite some differences in inclusion criteria between these studies, all required non-invasive vessel imaging to proof occlusion of a major brain supplying vessel. Furthermore, in most studies additional imaging techniques were used to exclude patients with already established large cerebral infarction or unfavorable collateral or penumbral status. Patients with small infarct volume, severe neurological deficits and in whom thrombectomy can be initiated within the first 6 hours after symptom onset seem to benefit the most. Therefore, mechanical thrombectomy using stent-retrievers in addition to intra-venous thrombolysis is recommended for the treatment of acute ischemic stroke with proven major vessel occlusion in the anterior circulation.

Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging.

PubMed

Uemura, Takeshi; Watanabe, Kenta; Ishibashi, Misaki; Saiki, Ryotaro; Kuni, Kyoshiro; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

2016-04-29

We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of combined high-intensity aerobic interval training program and Mediterranean diet recommendations after myocardial infarction (INTERFARCT Project): study protocol for a randomized controlled trial.

PubMed

Maldonado-Martín, Sara; Jayo-Montoya, Jon Ander; Matajira-Chia, Tatiana; Villar-Zabala, Beatriz; Goiriena, Juan José; Aispuru, G Rodrigo

2018-03-02

Exercise therapy has long been used for rehabilitation purposes after myocardial infarction (MI) and the benefit of regular physical exercise is also well-established. High-intensity interval training (HIIT) has been proposed to be more effective than continuous exercise for improving exercise capacity and health-related adaptations to low-volume (LV) and HIIT are also known. Furthermore, the Mediterranean diet (Mediet) has been widely reported to be a model of healthy eating for its contribution to a favorable health status and a better quality of life, reducing overall mortality. This study will investigate the effects of different HIIT programs (high-volume [HV] vs LV) and Mediet recommendations in clinical condition, cardiorespiratory fitness, biomarkers, ventricular function, and perception of quality of life after MI, and compared to an attention control group that is recommended to Mediet and physical activity without supervision sessions. In this randomized controlled trial, cardiorespiratory fitness, anthropometry, central and peripheral cardiovascular variables, biochemical and nutritional condition, and quality of life will be assessed before and after 16 weeks of intervention in 177 participants diagnosed with MI type 1. All participants will be randomly (1:1:1) assigned to the attention control group or two exercise groups (Mediet recommendations plus supervised aerobic exercise two days/week: (1) HV (40 min) HIIT group and (2) LV (20 min) HIIT group. This study will be the first clinical trial comparing the effects of two different volumes of HIIT programs with Mediet recommendations for people after MI. The results of this study will provide good evidence for physical rehabilitation in this population. ClinicalTrials.gov, NCT02876952 . Registered on 24 August 2016.

Neuroprotective effect of p-coumaric acid in mice with cerebral ischemia reperfusion injuries.

PubMed

Sakamula, Romgase; Thong-Asa, Wachiryah

2018-06-01

Cerebral ischemia reperfusion (IR) is associated with neuronal death, which leads to disability and cognitive decline. The pathomechanism occurs because ischemia is exacerbated during the reperfusion period. Neuronal damage susceptibility depends on the affected brain areas and the duration of ischemia. Prevention and supplementation to neurons may help them endure during IR and further benefit them in rehabilitation. We investigated the protective effect of p-coumaric acid (PC) on cerebral IR injuries in mice. We randomly divided 30 male ICR mice into 3 groups of Sham (received vehicle and not induced IR), Control-IR (received vehicle and induced IR) and PC-IR (received 100 mg/kg PC and induced IR). We orally administered vehicle or 100 mg/kg of p-coumaric acid for 2 weeks before inducing the cerebral IR injuries by using 30 min of a bilateral common carotid artery occlusion followed by a 45-min reperfusion. We induced the IR condition in the Control-IR and PC-IR groups but not the Sham group, and only the PC-IR group received p-coumaric acid. After IR induction, we sacrificed all the mice and collected their brain tissues to evaluate their oxidative statuses, whole brain infarctions and vulnerable neuronal deaths. We studied the whole-brain infarction volume by 2, 3, 5-triethyltetrazoliumchloride staining of sections. We performed a histological investigation of the vulnerable neuronal population in the dorsal hippocampus by staining brain sections with 0.1% cresyl violet. The results indicated that IR caused significant increases in calcium and malondialdehyde (MDA) levels, whole brain infarction volume and hippocampal neuronal death. Pretreatment with p-coumaric acid significantly reduced MDA levels, whole-brain infarction volume and hippocampal neuronal death together and increased catalase and superoxide dismutase activities. We conclude here that pretreating animals with p-coumaric acid can prevent IR-induced brain oxidative stress, infarction size and neuronal vulnerability to death in cerebral IR injuries.

Prominent hypointense veins on susceptibility weighted image in the cat brain with acute infarction: DWI, SWI, and PWI.

PubMed

Kim, Yong-Woo; Kim, Hak Jin; Choi, Seon Hee; Kim, Dong Chan

2014-10-01

The multiple prominent hypointense veins on susceptibility-weighted imaging (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. Venous side is the unknown area in the hemodynamics of brain infarction. To evaluate the venous aspect in acute brain infarction through an animal study. The acute infarction in cat brains was induced with a bolus infusion of 0.25 mL of triolein through one side of the common carotid artery. The magnetic resonance (MR) images, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, SW, and perfusion-weighted (PWI) images, were obtained serially at 2 h (n = 17), 1 day (n = 11), and 4 days (n = 4) after triolein infusion. The obtained MR images were evaluated qualitatively and quantitatively. For qualitative assessment, the signal intensity of the serial MR images was evaluated. The presence or absence and the location with serial changes of infarction were identified on DWI and ADC map images. The presence or absence of prominent hypointense veins and the serial changes of cortical veins were also evaluated on SWI. Quantitative assessment was performed by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit times (MTT) of the lesions with those of the contralateral normal side calculated on PWI. The serial changes of rCBV, rCBF, and MTT ratio were also evaluated. Acute infarction in the first and second medial gyrus of lesion hemisphere was found by qualitative evaluation of DWI and ADC map images. On the serial evaluation of SWI, the cortical veins of cat brain with infarction were obscured at 2 h and then re-appeared at 1 day. The hemorrhage transformation and prominent hypointense veins were seen at 4 days on SWI. The quantitative evaluation revealed increased MTT ratios and decreased rCBV and rCBF ratios on PWIs in the acute infarction of cat brain. The prominent hypointense veins on SWI were seen in the half of the acute infarction at 4 days. The prominent hypointense veins on SWI may have good agreement with the increased MTT ratio. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Human Dental Pulp Stem Cells Are More Effective Than Human Bone Marrow-Derived Mesenchymal Stem Cells in Cerebral Ischemic Injury.

PubMed

Song, Miyeoun; Lee, Jae-Hyung; Bae, Jinhyun; Bu, Youngmin; Kim, Eun-Cheol

2017-06-09

We compared the therapeutic effects and mechanism of transplanted human dental pulp stem cells (hDPSCs) and human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in a rat stroke model and an in vitro model of ischemia. Rats were intravenously injected with hDPSCs or hBM-MSCs 24 h after middle cerebral artery occlusion (MCAo), and both groups showed improved functional recovery and reduced infarct volume versus control rats, but the hDPSC group showed greater reduction in infarct volume than the hBM-MSC group. The positive area for the endothelial cell marker was greater in the lesion boundary areas in the hDPSC group than in the hBM-MSC group. Administration of hDPSCs to rats with stroke significantly decreased reactive gliosis, as evidenced by the attenuation of MCAo-induced GFAP+/nestin+ and GFAP+/Musashi-1+ cells, compared with hBM-MSCs. In vivo findings were confirmed by in vitro data illustrating that hDPSCs showed superior neuroprotective, migratory, and in vitro angiogenic effects in oxygen-glucose deprivation (OGD)-injured human astrocytes (hAs) versus hBM-MSCs. Comprehensive comparative bioinformatics analyses from hDPSC- and hBM-MSC-treated in vitro OGD-injured hAs were examined by RNA sequencing technology. In gene ontology and KEGG pathway analyses, significant pathways in the hDPSC-treated group were the MAPK and TGF-β signaling pathways. Thus, hDPSCs may be a better cell therapy source for ischemic stroke than hBM-MSCs.

Preclinical drug evaluation for combination therapy in acute stroke using systematic review, meta-analysis, and subsequent experimental testing

PubMed Central

O'Collins, Victoria E; Macleod, Malcolm R; Cox, Susan F; Van Raay, Leena; Aleksoska, Elena; Donnan, Geoffrey A; Howells, David W

2011-01-01

There is some evidence that in animal models of acute ischaemic stroke, combinations of neuroprotective agents might be more efficacious than the same agents administered alone. Hence, we developed pragmatic, empirical criteria based on therapeutic target, cost, availability, efficacy, administration, and safety to select drugs for testing in combination in animal models of acute stroke. Magnesium sulphate, melatonin, and minocycline were chosen from a library of neuroprotective agents, and were tested in a more ‘realistic' model favoured by the STAIR (Stroke Therapy Academic Industry Roundtable). Outcome was assessed with infarct volume, neurologic score, and two newly developed scales measuring general health and physiologic homeostasis. Owing to the failure to achieve neuroprotection in aged, hypertensive animals with drug delivery at 3 hours, the bar was lowered in successive experiments to determine whether neuroprotection could be achieved under conditions more conducive to recovery. Testing in younger animals showed more favourable homeostasis and general health scores than did testing in older animals, but infarct volume and neurologic scores did not differ with age, and treatment efficacy was again not shown. Testing with shorter occlusions resulted in smaller infarct volumes; nevertheless, treatment efficacy was still not observed. It was concluded that this combination, in these stroke models, was not effective. PMID:20978519

Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of ERK activity in ovariectomized mice.

PubMed

Wang, Shiquan; Wei, Haidong; Cai, Min; Lu, Yan; Hou, Wugang; Yang, Qianzi; Dong, Hailong; Xiong, Lize

2014-01-01

Stroke has severe consequences in postmenopausal women. As replacement therapy of estrogen have various adverse effects and the undermined outcomes. Genistein, a natural phytoestrogen, has been suggested to be a potential neuroprotective agent for such stroke patients. However, the role of genistein and its underlying mechanism in ovariectomized mice has not yet been evaluated. In the present study, ovariectomized mice were treated with genistein (10 mg/kg) or vehicle daily for two weeks before developing transient cerebral ischemia (middle cerebral artery occlusion). The neurological manifestation was evaluated, and infarct volumes were demonstrated by 2,3,5-triphenyltetrazolium chloride staining at 24 h after reperfusion. In addition, phosphorylation of extracellular signal-regulated kinase (ERK) was detected by Western blotting and immunofluorescence staining, and cellular apoptosis was evaluated in the ischemic penumbra. We found that treatment with genistein reduced infarct volumes, improved neurological outcomes and attenuated cellular apoptosis at 24 h after reperfusion. ERK1/2 showed increased phosphorylation by genistein treatment after reperfusion, and an ERK1/2 inhibitor U0126 abolished this protective effect of genistein in terms of infarct volumes, neurological scores and cellular apoptosis. Our findings indicate that treatment with genistein can reduce the severity of subsequent stroke episodes, and that this beneficial function is associated with ERK activation.

Spinal Cord Infarction in Clinical Neurology: A Review of Characteristics and Long-Term Prognosis in Comparison to Cerebral Infarction.

PubMed

Romi, Fredrik; Naess, Halvor

2016-01-01

Spinal cord stroke is rare accounting for 0.3-1% of all strokes and is classified into upper (cervical) and lower (thoracolumbar) strokes. Patients present with severe deficits but later often show good functional improvement. On admission, younger age, male gender, hypertension, diabetes mellitus and elevated blood glucose indicate more severe spinal cord strokes. Treatment of these risk factors is essential in the acute phase. Biphasic spinal cord strokes are seen in one-fifth of the patients. These present with acute or transient sensory spinal cord deficits often preceded by radiating pain between the shoulders, and should be considered and treated as imminent spinal cord strokes. Spinal cord infarction patients are younger and more often women compared to cerebral infarction patients. Traditional cerebrovascular risk factors are less relevant in spinal cord infarction. Spinal cord infarction patients are more likely to be discharged home and show better improvement after initial treatment compared to cerebral infarction patients. On long-term follow-up, spinal cord infarction patients have lower mortality and higher emotional well-being scores than cerebral infarction patients. Despite more chronic pain, the frequency of re-employment is higher among spinal cord infarction patients compared to cerebral infarction patients who are more often afflicted with cognitive function deficits. © 2016 S. Karger AG, Basel.

Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

PubMed

Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

2015-10-22

Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of engraftment of superparamagnetic iron oxide-labeled mesenchymal stem cells using three-dimensional reconstruction of magnetic resonance imaging in photothrombotic cerebral infarction models of rats.

PubMed

Shim, Jaehyun; Kwak, Byung Kook; Jung, Jisung; Park, Serah

2015-01-01

To evaluate engraftment by visualizing the location of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) three-dimensionally in photothrombotic cerebral infarction (PTCI) models of rats. Magnetic resonance imaging (MRI) of an agarose block containing superparamagnetic iron oxide (SPIO)-labeled hBM-MSCs was performed using a 3.0-T MRI, T2-(T2WI), T2(*)-(T2(*)WI), and susceptibility-weighted images (SWI). PTCI was induced in 6 rats, and 2.5 × 10(5) SPIO-labeled hBM-MSCs were infused through the ipsilateral internal carotid artery (ICA group) or tail vein (IV group). MRI was performed on days 1, 3, 7, and 14 after stem cell injection. Dark signal regions were confirmed using histology. Three-dimensional MRI reconstruction was performed using the clinical workflow solution to evaluate the engraftment of hBM-MSCs. Volumetric analysis of the engraftment was also performed. The volumes of SPIO-labeled hBM-MSCs in the phantom MRI were 129.3, 68.4, and 25.9 µL using SWI, T2(*)WI, and T2WI, respectively. SPIO-labeled hBM-MSCs appeared on day 1 after injection, encircling the cerebral infarction from the ventral side. Dark signal regions matched iron positive cells and human origin (positive) cells. The volume of the engraftment was larger in the ICA group on days 1, 3, and 7, after stem cell injection (p < 0.05 on SWI). SWI was the most sensitive MRI pulse sequence (p < 0.05). The volume of infarction decreased until day 14. The engraftment of SPIO-labeled hBM-MSCs can be visualized and evaluated three-dimensionally in PTCI models of rats. The engraftment volume was larger in the ICA group than IV group on early stage within one week.

Real-time three-dimensional echocardiographic study of left ventricular function after infarct exclusion surgery for ischemic cardiomyopathy

NASA Technical Reports Server (NTRS)

Qin, J. X.; Shiota, T.; McCarthy, P. M.; Firstenberg, M. S.; Greenberg, N. L.; Tsujino, H.; Bauer, F.; Travaglini, A.; Hoercher, K. J.; Buda, T.;

Upregulation of heme oxygenase-1 protected against brain damage induced by transient cerebral ischemia-reperfusion injury in rats.

PubMed

Lu, Xiufang; Gu, Renjun; Hu, Weimin; Sun, Zhitang; Wang, Gaiqing; Wang, Li; Xu, Yuming

2018-06-01

The aim of the present study was to identify the effect of heme oxygenase (HO)-1 gene on cerebral ischemia-reperfusion injury. Sprague-Dawley rats were divided randomly into four groups: Sham group, vehicle group, empty adenovirus vector (Ad) group and recombinant HO-1 adenovirus (Ad-HO-1) transfection group. Rats in the vehicle, Ad and Ad-HO-1 groups were respectively injected with saline, Ad or Ad-HO-1 for 3 days prior to cerebral ischemia-reperfusion injury. Subsequently, the middle cerebral artery occlusion method was used to establish the model of cerebral ischemia-reperfusion injury. Following the assessment of neurological function, rats were sacrificed, and the infarction volume and apoptotic index in rat brains were measured. Furthermore, the protein expression levels of HO-1 in brain tissues were detected using western blot analysis. Results indicated that the neurological score of the Ad-HO-1 group was significantly increased compared with the Ad or vehicle groups, respectively (P<0.001). The volume of cerebral infarction and the index score of neuronal apoptosis in the vehicle and Ad groups was significantly increased compared with the Ad-HO-1 group (P<0.01). The death of neuronal cells following cerebral ischemia-reperfusion injury reduced remarkably induced by over-expression of HO-1. These findings suggest a neuroprotective role of HO-1 against brain injury induced by transient cerebral ischemia-reperfusion injury.

Imaging predictors of poststroke depression: methodological factors in voxel-based analysis

PubMed Central

Gozzi, Sophia A; Wood, Amanda G; Chen, Jian; Vaddadi, Krishnarao; Phan, Thanh G

2014-01-01

Objective The purpose of this study was to explore the relationship between lesion location and poststroke depression using statistical parametric mapping. Methods First episode patients with stroke were assessed within 12 days and at 1-month poststroke. Patients with an a priori defined cut-off score of 11 on the Hospital Anxiety and Depression Scale (HADS) at follow-up were further assessed using the Mini-International Neuropsychiatric Interview (MINI) to confirm a clinical diagnosis of major or minor depression in accordance with Diagnostic and Statistical Manual-IV (DSM-IV) inclusion criteria. Participants were included if they were aged 18–85 years, proficient in English and eligible for MRI. Patients were excluded if they had a confounding diagnosis such as major depressive disorder at the time of admission, a neurodegenerative disease, epilepsy or an imminently life-threatening comorbid illness, subarachnoid or subdural stroke, a second episode of stroke before follow-up and/or a serious impairment of consciousness or language. Infarcts observed on MRI scans were manually segmented into binary images, linearly registered into a common stereotaxic coordinate space. Using statistical parametric mapping, we compared infarct patterns in patients with stroke with and without depression. Results 27% (15/55 patients) met criteria for depression at follow-up. Mean infarct volume was 19±53 mL and National Institute of Health Stroke Scale (NIHSS) at Time 1 (within 12 days of stroke) was 4±4, indicating a sample of mild strokes. No voxels or clusters were significant after a multiple comparison correction was applied (p>0.05). Examination of infarct maps showed that there was minimal overlap of infarct location between patients, thus invalidating the voxel comparison analysis. Conclusions This study provided inconclusive evidence for the association between infarcts in a specific region and poststroke depression. PMID:25001395

Clinical Predictors of Attention and Executive Functioning Outcomes in Children After Perinatal Arterial Ischemic Stroke.

PubMed

Bosenbark, Danielle D; Krivitzky, Lauren; Ichord, Rebecca; Vossough, Arastoo; Bhatia, Aashim; Jastrzab, Laura E; Billinghurst, Lori

2017-04-01

Children with perinatal arterial ischemic stroke (PAIS) are at risk for later neurocognitive and behavioral deficits, yet the clinical predictors of these outcomes are understudied. We examined the influence of clinical and infarct characteristics on attention and executive functioning in children following PAIS. Forty children born at term (≥37 weeks' gestation) with PAIS (28 with neonatal arterial ischemic stroke and 12 with presumed PAIS) underwent a comprehensive neuropsychological battery at age three to 16 years (median age 7.2 years; 58% male) to assess attention and executive functioning. Parents also completed questionnaires regarding real-world functioning. Clinical variables including perinatal stroke subtype, infarct characteristics (location, laterality, and volume), and the presence of comorbid epilepsy were ascertained from the medical record. Presumed PAIS, larger infarct volume, and comorbid epilepsy negatively influenced the performance on attention and executive functioning measures. These clinical variables were also associated with greater functional problems on parent reports, including a higher frequency of attention-deficit/hyperactivity disorder symptoms and greater difficulties in some subdomains of executive functioning. Infarct location and laterality were not associated with performance measures or parental report of functioning. Although all children with PAIS are at risk for later deficits in attention and executive functioning, those with presumed PAIS, larger infarct size, and comorbid epilepsy appear to be the most vulnerable. As they approach and reach school age, these children should undergo neuropsychological assessment to ensure timely implementation of therapeutic interventions and behavioral strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Thrombectomy in patients ineligible for iv tPA (THRILL).

PubMed

Bendszus, Martin; Thomalla, Götz; Knauth, Michael; Hacke, Werner; Bonekamp, Susanne; Fiehler, Jens

2015-08-01

A relevant proportion of patients with acute ischemic stroke are ineligible for intravenous thrombolysis with recombinant tissue plasminogen activator. Mechanical thrombectomy offers a treatment alternative for these patients; however, only few data are available on its safety and efficacy. The aim of this study was to compare safety and efficacy of stent retrievers as device class with best medical care alone in acute stroke patients with large intracranial vessel occlusion in the anterior circulation who are not eligible for intravenous thrombolysis with recombinant tissue plasminogen activator up to eight-hours of symptom onset. 'Thrombectomy in patients ineligible for iv tPA' is a prospective, open-label, blinded end-point, binational (Germany and Austria), two-arm, randomized, controlled, post-market study. Primary end-point is the modified Rankin Score shift analysis 90 days (±14) after stroke. Secondary end-points are excellent neurological outcomes (modified Rankin Score ≤ 1), good neurological outcomes (modified Rankin Score ≤ 2 or National Institutes of Health Stroke Scale improvement ≥ 10), difference between predicted infarct volume and actual core infarct volume (computed tomography or magnetic resonance imaging) at 30 (±6) h post-ictus, successful recanalization (thrombolysis in cerebral infarction score 2b or 3), functional health status 90 (±14) days after stroke (European Quality of Life-5 Dimensions) as well as common safety end-points (adverse event, serious adverse event, symptomatic intracranial haemorrhage at 30 (±6) h, death, or dependency). Whether mechanical thrombectomy in patients with acute ischemic stroke who are not eligible for intravenous thrombolysis with recombinant tissue plasminogen activator improves clinical outcomes is unclear. 'Thrombectomy in patients ineligible for iv tPA' may change clinical practice by providing evidence of an effective and safe treatment for such patients. © 2015 World Stroke Organization.

Nicotinamide Adenine Dinucleotide (NAD+) and Nicotinamide: Sex Differences in Cerebral Ischemia

PubMed Central

Siegel, Chad S.; McCullough, Louise D.

2013-01-01

Background Previous literature suggests that cell death pathways activated after cerebral ischemia differ between the sexes. While caspase-dependent mechanisms predominate in the female brain, caspase-independent cell death induced by activation of Poly (ADP-ribose) polymerase (PARP) predominates in the male brain. PARP-1 gene deletion decreases infarction volume in the male brain, but paradoxically increases damage in PARP-1 knockout females. Purpose This study examined stroke induced changes in NAD+, a key energy molecule involved in PARP-1 activation in both sexes. Methods Mice were subjected to Middle Cerebral Artery Occlusion and NAD+ levels were assessed. Caspase-3 activity and nuclear translocation was assessed 6 hours after ischemia. In additional cohorts, Nicotinamide (500mg/kg i.p.) a precursor of NAD+ or vehicle was administered and infarction volume was measured 24 hours after ischemia. Results Males have higher baseline NAD+ levels than females. Significant stroke-induced NAD+ depletion occurred in males and ovariectomized females but not in intact females. PARP-1 deletion prevented the stroke induced loss in NAD+ in males, but worsened NAD+ loss in PARP-1 deficient females. Preventing NAD+ loss with nicotinamide reduced infarct in wild-type males and PARP-1 knockout mice of both sexes, with no effect in WT females. Caspase-3 activity was significantly increased in PARP-1 knockout females compared to males and wild-type females, this was reversed with nicotinamide. Conclusions Sex differences exist in baseline and stroke-induced NAD+ levels. Nicotinamide protected males and PARP knockout mice, but had minimal effects in the wild-type female brain. This may be secondary to differences in energy metabolism between the sexes. PMID:23403179

IL-4 Is Required for Sex Differences in Vulnerability to Focal Ischemia in Mice.

PubMed

Xiong, Xiaoxing; Xu, Lijun; Wei, Liang; White, Robin E; Ouyang, Yi-Bing; Giffard, Rona G

2015-08-01

Interleukin (IL)-4 protects from middle cerebral artery occlusion in male mice. Females generally show less injury in response to the same ischemic challenge, but the underlying mechanisms are not fully understood. We tested the importance of IL-4 in female protection using IL-4 knockout (KO) mice. IL-4 KO and wild-type (WT) mice of both sexes were subjected to middle cerebral artery occlusion. Infarct volume was assessed by triphenyltetrazolium chloride staining and neurobehavioral outcome by neuroscore. T cell proliferation was assessed after Concanavalin A exposure. Ischemic brain immune cell populations were analyzed by fluorescence-activated cell sorting and immunostaining. Infarction in WT females during estrus and proestrus phases was significantly smaller than in males; neurological score was better. Infarction volume was larger and neurological score worse in IL-4 KO compared with WT in both sexes, with no sex difference. Proliferation of T cells was inhibited in WT females with higher proliferation and no sex difference in IL-4 KO. Macrophage numbers and total T cells in the ischemic hemisphere were lower in WT females, and monocytes increased markedly in IL-4 KOs with no sex difference. The reduced macrophage infiltration in WT-females was predominantly M2. Loss of IL-4 increased CD68+ and iNOS+ cells and reduced YM1+ and Arg1+ cells in both sexes. IL-4 is required for female neuroprotection during the estrus phase of the estrus cycle. Protected WT females show a predominance of M2-activated microglia/macrophages and reduced inflammatory infiltration. Increasing macrophage M2 polarization, with or without added inhibition of infiltration, may be a new approach to stroke treatment. © 2015 American Heart Association, Inc.

Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

PubMed Central

Reichert, Karla; Pereira do Carmo, Helison Rafael; Galluce Torina, Anali; Diógenes de Carvalho, Daniela; Carvalho Sposito, Andrei; de Souza Vilarinho, Karlos Alexandre; da Mota Silveira-Filho, Lindemberg; Martins de Oliveira, Pedro Paulo

2016-01-01

Purpose Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Methods Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. Results End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Conclusion Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events. PMID:27880844

Influence of manual thrombus aspiration on left ventricular diastolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

PubMed

Ilić, Ivan; Stanković, Ivan; Vidaković, Radosav; Janićijević, Aleksandra; Cerović, Milivoje; Jovanović, Vladimir; Aleksić, Aleksandar; Obradović, Gojko; Nikolajević, Ivica; Kafedzić, Srdjan; Milicević, Dusan; Kusić, Jovana; Putniković, Biljana; Nesković, Aleksandar N

2016-01-01

Data on effects of thrombus aspiration on left ventricular diastolic function in ST-elevation myocardial infarction (STEMI) population are scarce. We sought to compare echocardiographic indices of the diastolic function and outcomes in STEMI patients treated with and without manual thrombus aspiration, in an academic, high-volume percutaneous coronary intervention (PCI) center. A total of 433 consecutive patients who underwent primary PCI in 2011-2012 were enrolled in the study. Patients were not eligible for the study if they already suffered a myocardial infarction, had been previously revascularized, received thrombolytics, presented with cardiogenic shock, had significant valvular disease, atrial fibrillation or had previously implanted pacemaker. Comprehensive echocardiogram was performed within 48 hours. During follow-up patients'status was assessed by an office visit or telephone interview. Patients treated with thrombus aspiration (TA+, n=216) had similar baseline characteristics as those without thrombus aspiration (TA-, n = 217). Groups had similar total ischemic time (319 ± 276 vs. 333 ± 372 min; p = 0.665), but TA+ group had higher maximum values of troponin I (39.5 ± 30.5 vs. 27.6 ± 26.9 ng/ml; p < 0.001). The echocardiography revealed similar left ventricular volumes and systolic function, but TA+ group had significantly higher incidence of E/e' > 15, as a marker of severe diastolic dysfunction' (TA+ 23.1% vs. TA- 15.2%; p = 0.050). During average follow-up of 14 ± 5 months, major adverse cardiac/cerebral events occurred at the similar rate (log rank p = 0.867). Thrombus aspiration is associated with a greater incidence of severe diastolic dysfunction in unselected STEMI patients treated with primary PCI, but it doesn't influence the incidence of major adverse cardiovascular events.

Cholinergic stimulation with pyridostigmine improves autonomic function in infarcted rats.

PubMed

de La Fuente, Raquel N; Rodrigues, Bruno; Moraes-Silva, Ivana C; Souza, Leandro E; Sirvente, Raquel; Mostarda, Cristiano; De Angelis, Kátia; Soares, Pedro P; Lacchini, Silvia; Consolim-Colombo, Fernanda; Irigoyen, Maria-Cláudia

2013-09-01

In the present study we evaluated the effects of short-term pyridostigmine bromide (0.14 mg/mL) treatment started early after myocardial infarction (MI) on left ventricular (LV) and autonomic functions in rats. Male Wistar rats were divided into control, pyridostigmine, infarcted and infarcted + pyridostigmine-treated groups. Pyridostigmine was administered in the drinking water, starting immediately after MI or sham operation, for 11 days. Left ventricular function was evaluated indirectly by echocardiography and directly by LV catheterization. Cardiovascular autonomic control was evaluated by baroreflex sensitivity (BRS), heart rate variability (HRV) and pharmacological blockade. All evaluations started after 7 days pyridostigmine treatment and were finalized after 11 days treatment. Pyridostigmine prevented the impairment of +dP/dT and reduced the MI area in infarcted + pyridostigmine compared with infarcted rats (7 ± 3% vs 17 ± 4%, respectively). Mean blood pressure was restored in infarcted + pyridostigmine compared with infarcted rats (103 ± 3 vs 94 ± 3 mmHg, respectively). In addition, compared with the infarcted group, pyridostigmine improved BRS, as evaluated by tachycardic (1.6 ± 0.2 vs 2.5 ± 0.2 b.p.m./mmHg, respectively) and bradycardic (-0.42 ± 0.01 vs -1.9 ± 0.1 b.p.m./mmHg) responses, and reduced the low frequency/high frequency ratio of HRV (0.81 ± 0.11 vs 0.24 ± 0.14, respectively). These improvements are probably associated with increased vagal tone and reduced sympathetic tone in infarcted + pyridostigmine compared with infarcted rats. In conclusion, the data suggest that short-term pyridostigmine treatment started early after MI can improve BRS, HRV and parasympathetic and sympathetic tone in experimental rats. These data may have potential clinical implications because autonomic markers have prognostic significance after MI. © 2013 Wiley Publishing Asia Pty Ltd.

Infarct size in primary angioplasty without on-site cardiac surgical backup versus transferal to a tertiary center: a single photon emission computed tomography study.

PubMed

Knaapen, Paul; de Mulder, Maarten; van der Zant, Friso M; Peels, Hans O; Twisk, Jos W R; van Rossum, Albert C; Cornel, Jan H; Umans, Victor A W M

2009-02-01

Primary percutaneous coronary intervention (PCI) performed in large community hospitals without cardiac surgery back-up facilities (off-site) reduces door-to-balloon time compared with emergency transferal to tertiary interventional centers (on-site). The present study was performed to explore whether off-site PCI for acute myocardial infarction results in reduced infarct size. One hundred twenty-eight patients with acute ST-segment elevation myocardial infarction were randomly assigned to undergo primary PCI at the off-site center (n = 68) or to transferal to an on-site center (n = 60). Three days after PCI, (99m)Tc-sestamibi SPECT was performed to estimate infarct size. Off-site PCI significantly reduced door-to-balloon time compared with on-site PCI (94 +/- 54 versus 125 +/- 59 min, respectively, p < 0.01), although symptoms-to-treatment time was only insignificantly reduced (257 +/- 211 versus 286 +/- 146 min, respectively, p = 0.39). Infarct size was comparable between treatment centers (16 +/- 15 versus 14 +/- 12%, respectively p = 0.35). Multivariate analysis revealed that TIMI 0/1 flow grade at initial coronary angiography (OR 3.125, 95% CI 1.17-8.33, p = 0.023), anterior wall localization of the myocardial infarction (OR 3.44, 95% CI 1.38-8.55, p < 0.01), and development of pathological Q-waves (OR 5.07, 95% CI 2.10-12.25, p < 0.01) were independent predictors of an infarct size > 12%. Off-site PCI reduces door-to-balloon time compared with transferal to a remote on-site interventional center but does not reduce infarct size. Instead, pre-PCI TIMI 0/1 flow, anterior wall infarct localization, and development of Q-waves are more important predictors of infarct size.

Dragon's blood dropping pills have protective effects on focal cerebral ischemia rats model.

PubMed

Xin, Nian; Yang, Fang-Ju; Li, Yan; Li, Yu-Juan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Deng, Yu-Lin

2013-12-15

Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (p<0.01) and reduce cerebral infarct volume of focal cerebral ischemia rats remarkably (p<0.05-0.01). Meanwhile, each group could alleviate cerebral water content and cerebral index (p<0.05-0.01) and regulate oxidative stress of focal cerebral ischemia rats obviously (p<0.05-0.01). Activities of middle group corresponded with that treated with positive control drug. The results obtained here showed that Dragon's blood dropping pills had protective effects on focal cerebral ischemia rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

Nicotinamide attenuates the ischemic brain injury-induced decrease of Akt activation and Bad phosphorylation.

PubMed

Koh, Phil-Ok

2011-07-08

Nicotinamide protects cortical neuronal cells against cerebral ischemic injury through activation of various cytoprotective mechanisms. Here, this study confirmed the neuroprotective effects of nicotinamide in focal cerebral ischemic injury and investigated whether nicotinamide modulates a crucial survival pathway, Akt and its downstream targets. Adult male rats were treated with vehicle or nicotinamide (500 mg/kg) 2h after the onset of middle cerebral artery occlusion (MCAO). Brains were collected 24h after MCAO and infarct volumes were analyzed. Nicotinamide significantly reduced the infarct volume in the cerebral cortex. Potential activation was measured by phosphorylation of PDK1 at Ser(241), Akt at Ser(473), and Bad at Ser(136) using Western blot analysis. Nicotinamide prevented the injury-induced decrease of pPDK1, pAkt, and pBad levels. 14-3-3 levels were not different between vehicle- and nicotinamide-treated animals. However, pBad and 14-3-3 interaction levels decreased during MCAO, but were maintained in the presence of nicotinamide, compared to levels in control animals. These findings suggest that nicotinamide attenuates cell death due to focal cerebral ischemic injury and that neuroprotective effects are mediated through the Akt signaling pathway, thus enhancing neuronal survival. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Correlation of symptom depression levels with mean platelet volume rate on patients of acute coronary syndrome

NASA Astrophysics Data System (ADS)

Hasugian, L.; Hanum, H.; Hanida, W.; Safri, Z.

2018-03-01

Patients with Depression and the acute coronary syndrome (ACS) is rarely detected, although in some studies say that depression can worsen cardiovascularly and increase mortality. From research, Canan F et al found that increasing levels of Mean platelet volume (MPV) as a risk factor for atherosclerosis and MPV was higher in patients with depression compared with patients without depression. In this study used observational methods of measurement of cross-sectional data. Research began in November 2015 - May 2016 against General Hospital inpatients H. Adam Malik Medan. There are 64 patients with a diagnosis of ACS were given quieter Beck Depression Inventory (BDI), then calculated a score of BDI patients and MPV levels were seen when they first entered the hospital before being given treatment. Patients answered quieter on days 3-7 after diagnosis ACS. ACS Patients were divided into 3 groups: acute myocardial infarction with ST elevation, acute myocardial infarction with non-ST elevation and unstable angina pectoris. The level of depression is grouped into not depression, mild depression, moderate depression and severe depression. Statistically significant with p-value<0.05Based on the linear correlation analysis, it was found a positive correlation with r=0.542. And the relationship is statistically significant with p-value 0.000003.

Sex-dependent effects of G protein-coupled estrogen receptor activity on outcome after ischemic stroke.

PubMed

Broughton, Brad R S; Brait, Vanessa H; Kim, Hyun Ah; Lee, Seyoung; Chu, Hannah X; Gardiner-Mann, Chantelle V; Guida, Elizabeth; Evans, Megan A; Miller, Alyson A; Arumugam, Thiruma V; Drummond, Grant R; Sobey, Christopher G

2014-03-01

Experimental studies indicate that estrogen typically, but not universally, has a neuroprotective effect in stroke. Ischemic stroke increases membrane-bound G protein-coupled estrogen receptor (GPER) distribution and expression in the brain of male but not female mice. We hypothesized that GPER activation may have a greater neuroprotective effect in males than in females after stroke. Vehicle (dimethyl sulfoxide), a GPER agonist (G-1, 30 μg/kg), or a GPER antagonist (G-15, 300 μg/kg) were administered alone or in combination to young or aged male mice, or young intact or ovariectomized female mice, 1 hour before or 3 hours after cerebral ischemia-reperfusion. Some mice were treated with a combination of G-1 and the pan-caspase inhibitor, quinoline-Val-Asp(Ome)-CH2-O-phenoxy (Q-VD-OPh), 1 hour before stroke. We evaluated functional and histological end points of stroke outcome up to 72 hours after ischemia-reperfusion. In addition, apoptosis was examined using cleaved caspase-3 immunohistochemistry. Surprisingly, G-1 worsened functional outcomes and increased infarct volume in males poststroke, in association with an increased expression of cleaved caspase-3 in peri-infarct neurons. These effects were blocked by G-15 or Q-VD-OPh. Conversely, G-15 improved functional outcomes and reduced infarct volume after stroke in males, whether given before or after stroke. In contrast to findings in males, G-1 reduced neurological deficit, apoptosis, and infarct volume in ovariectomized females, but had no significant effect in intact females. Future therapies for acute stroke could exploit the modulation of GPER activity in a sex-specific manner.

Remote Zone Extracellular Volume and Left Ventricular Remodeling in Survivors of ST-Elevation Myocardial Infarction.

PubMed

Carberry, Jaclyn; Carrick, David; Haig, Caroline; Rauhalammi, Samuli M; Ahmed, Nadeem; Mordi, Ify; McEntegart, Margaret; Petrie, Mark C; Eteiba, Hany; Hood, Stuart; Watkins, Stuart; Lindsay, Mitchell; Davie, Andrew; Mahrous, Ahmed; Ford, Ian; Sattar, Naveed; Welsh, Paul; Radjenovic, Aleksandra; Oldroyd, Keith G; Berry, Colin

2016-08-01

The natural history and pathophysiological significance of tissue remodeling in the myocardial remote zone after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. Extracellular volume (ECV) in myocardial regions of interest can now be measured with cardiac magnetic resonance imaging. Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [British Heart Foundation Magnetic Resonance Imaging in Acute ST-Segment Elevation Myocardial Infarction study]). Cardiac magnetic resonance was performed at 1.5 Tesla at 2 days and 6 months post STEMI. T1 modified Look-Locker inversion recovery mapping was performed before and 15 minutes after contrast (0.15 mmol/kg gadoterate meglumine) in 140 patients at 2 days post STEMI (mean age: 59 years, 76% male) and in 131 patients at 6 months post STEMI. Remote zone ECV was lower than infarct zone ECV (25.6±2.8% versus 51.4±8.9%; P<0.001). In multivariable regression, left ventricular ejection fraction was inversely associated with remote zone ECV (P<0.001), and diabetes mellitus was positively associated with remote zone ECV (P=0.010). No ST-segment resolution (P=0.034) and extent of ischemic area at risk (P<0.001) were multivariable associates of the change in remote zone ECV at 6 months (ΔECV). ΔECV was a multivariable associate of the change in left ventricular end-diastolic volume at 6 months (regression coefficient [95% confidence interval]: 1.43 (0.10-2.76); P=0.036). ΔECV is implicated in the pathophysiology of left ventricular remodeling post STEMI, but because the effect size is small, ΔECV has limited use as a clinical biomarker of remodeling. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02072850. © 2016 The Authors.

Remote Zone Extracellular Volume and Left Ventricular Remodeling in Survivors of ST-Elevation Myocardial Infarction

PubMed Central

Carberry, Jaclyn; Carrick, David; Haig, Caroline; Rauhalammi, Samuli M.; Ahmed, Nadeem; Mordi, Ify; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Hood, Stuart; Watkins, Stuart; Lindsay, Mitchell; Davie, Andrew; Mahrous, Ahmed; Ford, Ian; Sattar, Naveed; Welsh, Paul; Radjenovic, Aleksandra; Oldroyd, Keith G.

2016-01-01

The natural history and pathophysiological significance of tissue remodeling in the myocardial remote zone after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. Extracellular volume (ECV) in myocardial regions of interest can now be measured with cardiac magnetic resonance imaging. Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [British Heart Foundation Magnetic Resonance Imaging in Acute ST-Segment Elevation Myocardial Infarction study]). Cardiac magnetic resonance was performed at 1.5 Tesla at 2 days and 6 months post STEMI. T1 modified Look-Locker inversion recovery mapping was performed before and 15 minutes after contrast (0.15 mmol/kg gadoterate meglumine) in 140 patients at 2 days post STEMI (mean age: 59 years, 76% male) and in 131 patients at 6 months post STEMI. Remote zone ECV was lower than infarct zone ECV (25.6±2.8% versus 51.4±8.9%; P<0.001). In multivariable regression, left ventricular ejection fraction was inversely associated with remote zone ECV (P<0.001), and diabetes mellitus was positively associated with remote zone ECV (P=0.010). No ST-segment resolution (P=0.034) and extent of ischemic area at risk (P<0.001) were multivariable associates of the change in remote zone ECV at 6 months (ΔECV). ΔECV was a multivariable associate of the change in left ventricular end-diastolic volume at 6 months (regression coefficient [95% confidence interval]: 1.43 (0.10–2.76); P=0.036). ΔECV is implicated in the pathophysiology of left ventricular remodeling post STEMI, but because the effect size is small, ΔECV has limited use as a clinical biomarker of remodeling. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT02072850. PMID:27354423

Treatment of experimental stroke with IL-10-producing B-cells reduces infarct size and peripheral and CNS inflammation in wild-type B-cell-sufficient mice

PubMed Central

Bodhankar, Sheetal; Chen, Yingxin; Vandenbark, Arthur A.; Murphy, Stephanie J.; Offner, Halina

2014-01-01

Clinical stroke induces inflammatory processes leading to cerebral and splenic injury and profound peripheral immunosuppression. IL-10 expression is elevated during major CNS diseases and limits inflammation in the brain. Recent evidence demonstrated that absence of B-cells led to larger infarct volumes and CNS damage after middle cerebral artery occlusion (MCAO) that could be prevented by transfer of IL-10+ B-cells. The purpose of this study was to determine if the beneficial immunoregulatory effects on MCAO of the IL-10+ B-cell subpopulation also extends to B-cell-sufficient mice that would better represent stroke subjects. CNS inflammation and infarct volumes were evaluated in male C57BL/6J (WT) mice that received either RPMI or IL-10+ B-cells and underwent 60 min of middle cerebral artery occlusion (MCAO) followed by 96 hours of reperfusion. Transfer of IL-10+ B-cells markedly reduced infarct volume in WT recipient mice when given 24 hours prior to or 4 hours after MCAO. B-cell protected MCAO mice had increased regulatory subpopulations in the periphery, reduced numbers of activated, inflammatory T-cells, decreased infiltration of T-cells and a less inflammatory milieu in the ischemic hemispheres of the IL-10+ B-cell-treated group. Moreover, transfer of IL-10+ B-cells 24 hours before MCAO led to a significant preservation of regulatory immune subsets in the IL-10+ B-cell protected group presumably indicating their role in immunomodulatory mechanisms, post-stroke. Our studies are the first to demonstrate a major immunoregulatory role for IL-10+ regulatory B-cells in preventing and treating MCAO in WT mice and also implicating their potential role in attenuating complications due to post-stroke immunosuppression. PMID:24374817

Protective effect of hexane extracts of Uncaria sinensis against photothrombotic ischemic injury in mice.

PubMed

Park, Sun Haeng; Kim, Ji Hyun; Park, Se Jin; Bae, Sun Sik; Choi, Young Whan; Hong, Jin Woo; Choi, Byung Tae; Shin, Hwa Kyoung

2011-12-08

Uncaria sinensis (US) has been used in traditional Korean medicine to treat vascular disease and to relieve various neurological symptoms. Scientific evidence related to the effectiveness or action mechanism of US on cerebrovascular disease has not been examined experimentally. Here, we investigated the cerebrovascular protective effect of US extracts on photothrombotic ischemic injury in mice. US hexane extracts (HEUS), ethyl acetate extracts (EAEUS) and methanol extracts (MEUS) were administered intraperitoneally 30 min before ischemic insults. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, neurological score and the activation of Akt and eNOS in ischemic brain. HEUS more significantly reduced infarct volume and edema than did EAEUS and MEUS following photothrombotic cortical occlusion. HEUS produced decreased infarct volume and edema size, and improved neurological function in a concentration-dependent manner (10, 50, and 100 mg/kg). However, HEUS did not reduce brain infarction in eNOS KO mice, suggesting that the protective effect of HEUS is primarily endothelium-dependent. Furthermore, HEUS (10-300 μg/ml) produced a concentration-dependent relaxation in mouse aorta and rat basilar artery, which was not seen in eNOS KO mouse aorta, suggesting that HEUS cause vasodilation via an eNOS-dependent mechanism. This correlated with increased phosphorylation of Akt and eNOS in the brains of HEUS-treated mice. HEUS prevent cerebral ischemic damage by regulating Akt/eNOS signaling. US, herbal medicine, may be the basis of a novel strategy for the therapy of stroke. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A simple brain atrophy measure improves the prediction of malignant middle cerebral artery infarction by acute DWI lesion volume.

PubMed

Beck, Christoph; Kruetzelmann, Anna; Forkert, Nils D; Juettler, Eric; Singer, Oliver C; Köhrmann, Martin; Kersten, Jan F; Sobesky, Jan; Gerloff, Christian; Fiehler, Jens; Schellinger, Peter D; Röther, Joachim; Thomalla, Götz

2014-06-01

In patients with malignant middle cerebral artery infarction (MMI) decompressive surgery within 48 h improves functional outcome. In this respect, early identification of patients at risk of developing MMI is crucial. While the acute diffusion weighted imaging (DWI) lesion volume was found to predict MMI with high predictive values, the potential impact of preexisting brain atrophy on the course of space-occupying middle cerebral artery (MCA) infarction and the development of MMI remains unclear. We tested the hypothesis that the combination of the acute DWI lesion volume with simple measures of brain atrophy improves the early prediction of MMI. Data from a prospective, multicenter, observational study, which included patients with acute middle cerebral artery main stem occlusion studied by MRI within 6 h of symptom onset, was analyzed retrospectively. The development of MMI was defined according to the European randomized controlled trials of decompressive surgery. Acute DWI lesion volume, as well as brain and cerebrospinal fluid volume (CSF) were delineated. The intercaudate distance (ICD) was assessed as a linear brain atrophy marker by measuring the hemi-ICD of the intact hemisphere to account for local brain swelling. Binary logistic regression analysis was used to identify significant predictors of MMI. Cut-off values were determined by Classification and Regression Trees analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the resulting models were calculated. Twenty-one (18 %) of 116 patients developed a MMI. Malignant middle cerebral artery infarctions patients had higher National Institutes of Health Stroke Scale scores on admission and presented more often with combined occlusion of the internal carotid artery and MCA. There were no differences in brain and CSF volume between the two groups. Diffusion weighted imaging lesion volume was larger (p < 0.001), while hemi-ICD was smaller (p = 0.029) in MMI patients. Inclusion of hemi-ICD improved the prediction of MMI. Best cut-off values to predict the development of MMI were DWI lesion volume > 87 ml and hemi-ICD ≤ 9.4 mm. The addition of hemi-ICD to the decision tree strongly increased PPV (0.93 vs. 0.70) resulting in a reduction of false positive findings from 7/23 (30 %) to 1/15 (7 %), while there were only slight changes in specificity, sensitivity and NPV. The absolute number of correct classifications increased by 4 (3.4 %). The integration of hemi-ICD as a linear marker of brain atrophy, that can easily be assessed in an emergency setting, may improve the prediction of MMI by lesion volume based predictive models.

Plaque shift and distal embolism in patients with acute myocardial infarction: a volumetric intravascular ultrasound analysis from the HORIZONS-AMI trial.

PubMed

Wu, Xiaofan; Maehara, Akiko; He, Yong; Xu, Kai; Oviedo, Carlos; Witzenbichler, Bernhard; Lansky, Alexandra J; Dressler, Ovidiu; Parise, Helen; Stone, Gregg W; Mintz, Gary S

2013-08-01

Vessel expansion and axial plaque redistribution or distal plaque embolization contribute to the increase in lumen dimensions after stent implantation. Preintervention and postintervention grayscale volumetric intravascular ultrasound was used to study 43 de novo native coronary lesions treated with TAXUS or Express bare metal stents in the HORIZONS-AMI Trial. There was a decrease in lesion segment plaque + media (P + M) volume (-19.5 ± 22.2 mm(3) ) that was associated with a decrease in overall analysis segment (lesion plus 5 mm long proximal and distal reference segments) P + M volume (-17.5 ± 21.0 mm(3) ) that was greater than the shift of plaque from the lesion to the proximal and distal reference segments (1.9 ± 4.5 mm(3) , P < 0.0001). Overall analysis segment P + M volume decreased more in the angiographic thrombus (+) versus the thrombus (-) group (27.4 ± 23.4 vs. -8.9 ± 14.3 mm(3) , P = 0.003), whereas plaque shift to the reference segments showed no significant difference between the two groups (1.5 ± 5.2 vs. 2.3 ± 3.9 mm(3) , P = 0.590). Compared with the angiographic thrombus (-) group, patients in the thrombus (+) group more often developed no reflow (25% vs. 0%, P = 0.012) and had a higher preintervention CK-MB (P = 0.011), postintervention CK-MB (P < 0.001), and periprocedural (post-PCI minus pre-PCI) elevation of CK-MB (P = 0.001). In acute myocardial infarction lesions, there was a marked poststenting reduction in overall plaque volume that was significantly greater in patients with angiographic thrombus than without thrombus and may have explained a greater periprocedural rise in CK-MB. © 2013 Wiley Periodicals, Inc.

A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice.

PubMed

Ronca, Richard D; Myers, Alyssa M; Ganea, Doina; Tuma, Ronald F; Walker, Ellen A; Ward, Sara Jane

2015-10-01

We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size. Mice received three injections of the CB2 selective agonist O-1966 or vehicle 1h prior to and 2 and 5days following induction of stroke. Infarct size was assessed at 1, 3, or 7days post-injury and learning and memory effects of injury and O-1966 treatment were assessed on days 6 and 7 using a novel object recognition task and an operant acquisition and retention procedure. O-1966 treated mice had significantly smaller infarct volumes compared with vehicle treated mice. Photoinjury was also associated with a significant memory impairment on day 7 post-injury, and this deficit was reversed with O-1966 treatment. Surprisingly, sham-operated mice receiving O-1966 treatment showed a significant learning deficit in both the recognition and operant tasks compared with vehicle treated sham mice. We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia, but may dysregulate glial or neuronal function of learning and memory circuits in the absence of injury and/or inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

The neuroprotective effects of intravascular low level laser irradiation on cerebral ischemia rats

NASA Astrophysics Data System (ADS)

Qiu, Yongming; Lu, Zhaofeng; Wang, Zhongguang; Jiang, Jiyao

2005-07-01

The effects of intravascular low level laser irradiation of He-Ne on rat MCAo-induced cerebral injury were studied. The results showed that control rats (subjected to MCAo injury without laser treatment) at 7d exhibited striatal and cortical brain infarction in the right hemisphere from approximately 3 to 11mm from the front pole. the total infarct volume in this group was 34.5+/-8.1mm3. For experimental rats (with laser management), the total infarct volume was 29.0+/-9.0mm3. P was gained less than 0.05. The neurological score of control group was 4.7+/-0.6 and it was 5.2+/-1.0 in experimental group, comparison by statistical analysis showed P less than 0.05. The cerebral pathological damages in the control group were more severe than in experimental group. We concluded that the intravascular low level laser irradiation has no remarked complication and is helpful to reduce ischemic damage. There is clinically potential for the application of intravascular He-Ne low level laser irradiation in ischemia stroke.

Infarct size, left ventricular function, and prognosis in women compared to men after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: results from an individual patient-level pooled analysis of 10 randomized trials.

PubMed

Kosmidou, Ioanna; Redfors, Björn; Selker, Harry P; Thiele, Holger; Patel, Manesh R; Udelson, James E; Magnus Ohman, E; Eitel, Ingo; Granger, Christopher B; Maehara, Akiko; Kirtane, Ajay; Généreux, Philippe; Jenkins, Paul L; Ben-Yehuda, Ori; Mintz, Gary S; Stone, Gregg W

2017-06-01

Studies have reported less favourable outcomes in women compared with men after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI). Whether sex-specific differences in the magnitude or prognostic impact of infarct size or post-infarction cardiac function explain this finding is unknown. We pooled patient-level data from 10 randomized primary PCI trials in which infarct size was measured within 1 month (median 4 days) by either cardiac magnetic resonance imaging or technetium-99m sestamibi single-photon emission computed tomography. We assessed the association between sex, infarct size, and left ventricular ejection fraction (LVEF) and the composite rate of death or heart failure (HF) hospitalization within 1 year. Of 2632 patients with STEMI undergoing primary PCI, 587 (22.3%) were women. Women were older than men and had a longer delay between symptom onset and reperfusion. Infarct size did not significantly differ between women and men, and women had higher LVEF. Nonetheless, women had a higher 1-year rate of death or HF hospitalization compared to men, and while infarct size was a strong independent predictor of 1-year death or HF hospitalization (P < 0.0001), no interaction was present between sex and infarct size or LVEF on the risk of death or HF hospitalization. In this large-scale, individual patient-level pooled analysis of patients with STEMI undergoing primary PCI, women had a higher 1-year rate of death or HF hospitalization compared to men, a finding not explained by sex-specific differences in the magnitude or prognostic impact of infarct size or by differences in post-infarction cardiac function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Impaired Cerebral Autoregulation Is Associated with Brain Atrophy and Worse Functional Status in Chronic Ischemic Stroke

PubMed Central

Aoi, Mikio C.; Hu, Kun; Lo, Men-Tzung; Selim, Magdy; Olufsen, Mette S.; Novak, Vera

2012-01-01

Dynamic cerebral autoregulation (dCA) is impaired following stroke. However, the relationship between dCA, brain atrophy, and functional outcomes following stroke remains unclear. In this study, we aimed to determine whether impairment of dCA is associated with atrophy in specific regions or globally, thereby affecting daily functions in stroke patients. We performed a retrospective analysis of 33 subjects with chronic infarctions in the middle cerebral artery territory, and 109 age-matched non-stroke subjects. dCA was assessed via the phase relationship between arterial blood pressure and cerebral blood flow velocity. Brain tissue volumes were quantified from MRI. Functional status was assessed by gait speed, instrumental activities of daily living (IADL), modified Rankin Scale, and NIH Stroke Score. Compared to the non-stroke group, stroke subjects showed degraded dCA bilaterally, and showed gray matter atrophy in the frontal, parietal and temporal lobes ipsilateral to infarct. In stroke subjects, better dCA was associated with less temporal lobe gray matter atrophy on the infracted side ( = 0.029), faster gait speed ( = 0.018) and lower IADL score (0.002). Our results indicate that better dynamic cerebral perfusion regulation is associated with less atrophy and better long-term functional status in older adults with chronic ischemic infarctions. PMID:23071639

Combining MRI With PET for Partial Volume Correction Improves Image-Derived Input Functions in Mice

NASA Astrophysics Data System (ADS)

Evans, Eleanor; Buonincontri, Guido; Izquierdo, David; Methner, Carmen; Hawkes, Rob C.; Ansorge, Richard E.; Krieg, Thomas; Carpenter, T. Adrian; Sawiak, Stephen J.

2015-06-01

Accurate kinetic modelling using dynamic PET requires knowledge of the tracer concentration in plasma, known as the arterial input function (AIF). AIFs are usually determined by invasive blood sampling, but this is prohibitive in murine studies due to low total blood volumes. As a result of the low spatial resolution of PET, image-derived input functions (IDIFs) must be extracted from left ventricular blood pool (LVBP) ROIs of the mouse heart. This is challenging because of partial volume and spillover effects between the LVBP and myocardium, contaminating IDIFs with tissue signal. We have applied the geometric transfer matrix (GTM) method of partial volume correction (PVC) to 12 mice injected with 18F - FDG affected by a Myocardial Infarction (MI), of which 6 were treated with a drug which reduced infarction size [1]. We utilised high resolution MRI to assist in segmenting mouse hearts into 5 classes: LVBP, infarcted myocardium, healthy myocardium, lungs/body and background. The signal contribution from these 5 classes was convolved with the point spread function (PSF) of the Cambridge split magnet PET scanner and a non-linear fit was performed on the 5 measured signal components. The corrected IDIF was taken as the fitted LVBP component. It was found that the GTM PVC method could recover an IDIF with less contamination from spillover than an IDIF extracted from PET data alone. More realistic values of Ki were achieved using GTM IDIFs, which were shown to be significantly different (p <; 0.05) between the treated and untreated groups.

An experimental investigation of bubble splitting through multiple bifurcations

NASA Astrophysics Data System (ADS)

Bull, Joseph L.; Eshpuniyani, Brijesh; Fowlkes, J. Brian

2004-11-01

A bench top vascular bifurcation model is used to investigate the splitting of long bubbles in a series of liquid-filled bifurcations. These experiments are motivated by a gas embolotherapy technique for the potential treatment of cancer by using gas emboli to infarct tumors. The gas bubbles originate as perfluorocarbon droplets that are small enough to pass through capillaries and are injected into the bloodstream. Low intensity ultrasound is used to track their motion, and they are vaporized at the desired location for treatment via high intensity ultrasound to produce gas bubbles whose volumes are approximately 125 to 150 times the droplet volume. Achieving complete tumor necrosis requires infarction of most of the tumor. Understanding the transport and splitting of the gas bubbles, which can be long enough to extend through more than one bifurcation, is necessary to design delivery strategies. The current experiments investigate the behavior of a bubble as it passes through a series of two geometrically symmetric bifurcations, for different values of effective Bond number, which depends on gravity and the positioning of the bifurcation, capillary number, and bubble volume. The experiments are designed to match the Reynolds, Bond and capillary numbers to the physiological values for arterioles, and to provide guidance in achieving uniform tumor infarction. This work is supported by NSF grant BES-0301278 and NIH grant EB003541-01.

Effects of intravenous dimethyl sulfoxide on ischemia evolution in a rat permanent occlusion model

PubMed Central

Bardutzky, Juergen; Meng, Xianjun; Bouley, James; Duong, Timothy Q; Ratan, Rajiv; Fisher, Marc

2010-01-01

Dimethyl sulfoxide (DMSO) has a variety of biological actions that suggest efficacy as a neuroprotectant. We (1) tested the neuroprotective potential of DMSO at different time windows on infarct size using 2,3,5-triphenyltetrazolium staining and (2) investigated the effects of DMSO on ischemia evolution using quantitative diffusion and perfusion imaging in a permanent middle cerebral artery occlusion (MCAO) model in rats. In experiment 1, DMSO treatment (1.5 g/kg intravenously over 3 h) reduced infarct volume 24 h after MCAO by 65% (P<0.00001) when initiated 20 h before MCAO, by 44% (P=0.0006) when initiated 1 h after MCAO, and by 17% (P=0.11) when started 2 h after MCAO. Significant infarct reduction was also observed after a 3-day survival in animals treated 1 h after MCAO (P=0.005). In experiment 2, treatment was initiated 1 h after MCAO and maps for cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were acquired before treatment and then every 30 mins up to 4 h. Cerebral blood flow characteristics and CBF-derived lesion volumes did not differ between treated and untreated animals, whereas the ADC-derived lesion volume essentially stopped progressing during DMSO treatment, resulting in a persistent diffusion/perfusion mismatch. This effect was mainly observed in the cortex. Our data suggest that DMSO represents an interesting candidate for acute stroke treatment. PMID:15744247

Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

PubMed

Luo, Da; Hu, Huihui; Qin, Zhiliang; Liu, Shan; Yu, Xiaomei; Ma, Ruisong; He, Wenbo; Xie, Jing; Lu, Zhibing; He, Bo; Jiang, Hong

2017-12-01

Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing. Copyright © 2017 Elsevier B.V. All rights reserved.

Natural history of the spontaneous reperfusion of human cerebral infarcts as assessed by 99mTc HMPAO SPECT

PubMed Central

Bowler, J; Wade, J; Jones, B; Nijran, K; Steiner, T

1998-01-01

OBJECTIVE—Little is known about the effect of spontaneous reperfusion of human cerebral infarcts. Single photon emission computerised tomography (SPECT) data were analysed from a study using 99Tcm HMPAO (99Tcm hexamethylpropyleneamine oxime) in human cerebral infarction for the frequency of reperfusion and to see if it affected infarct size, oedema, haemorrhagic transformation, or functional outcome.
METHODS—Fifty sequential cases of ischaemic stroke were studied with 124 99Tcm HMPAO SPECT at around one day, one week, and three months after stroke along with detailed clinical and functional assessments.
RESULTS—Visually apparent reperfusion occurred in 14 of 50 patients (28%) with a mean delay of 5.8 days and reperfusion was seen in seven others in whom it was identified on the basis of changes in perfusion deficit volume. It occurred in 13 of 23 embolic events but only in three of 23 other events. In only two cases did spontaneous reperfusion occur early enough to preserve tissue or function. Reperfusion did not otherwise reduce infarct size, or improve clinical or functional outcome, and was not associated with oedema but an association with haemorrhagic transformation was suggested. Reperfusion significantly decreased the apparent perfusion defect as measured by SPECT one week from the ictus, but was mostly non-nutritional and transient. The mean volume of tissue preserved by nutritional reperfusion was 10 cm3, but this was unequally distributed between cases. Late washout of 99Tcm HMPAO from areas of hyperaemic reperfusion may be a good prognostic marker but is a rare phenomenon and too insensitive to be of general applicability.
CONCLUSIONS—Spontaneous reperfusion after cerebral infarction occurs in 42% of cases within the first week but is associated with clinical improvement in only 2%. It has few adverse consequences although it may be associated with haemorrhagic transformation.

 PMID:9436735

Very Mild Hypothermia (35°C) Postischemia Reduces Infarct Volume and Blood/Brain Barrier Breakdown Following tPA Treatment in the Mouse.

PubMed

Cechmanek, Brian K; Tuor, Ursula I; Rushforth, David; Barber, Philip A

2015-12-01

Reperfusion therapies for stroke diminish in effectiveness and safety as time to treatment increases. Hypothermia neuroprotection for stroke is established, but its clinical translation has been hampered by uncertainties regarding optimal temperature and complications associated with moderate hypothermia. Also, hypothermia targeting temperatures of 32-33°C is associated with clinical and logistical problems related to induction and adverse side effects. We hypothesized that ischemic damage and tPA-exacerbated blood/brain barrier (BBB) breakdown produced following 30 minutes of middle cerebral artery occlusion and either 1 hour of saline or tPA infusion would be reduced by treatment with very mild cooling of 1.5°C for 48 hours followed by 24 hours of gradual rewarming. Infarct volume was reduced by 29.6% (p<0.001) and 41.9% (p<0.001) in hypothermic-tPA (Hypo_tPA)-treated and hypothermic-saline (Hypo_Sal)-treated animals compared to normothermic-tPA (Norm_tPA) and saline (Norm_Sal)-treated animals, respectively. Hypothermia also reduced IgG extravasation in tPA-treated, but not saline-treated groups compared to their normothermic controls (p<0.001). The ipsilateral-contralateral changes in optical density for IgG extravasation were 18.4% greater in the Norm_tPA than Norm_Sal (p<0.001) group. The ipsilateral-contralateral changes in optical density for IgG extravasation were reduced by 17.8% (p<0.001) in the Hypo_tPA compared to Norm_tPA group. No significant mean difference in IgG extravasation was seen between Hypo_tPA and Hypo_Sal groups (p>0.05). Very modest hypothermia to reduce the BBB breakdown could improve the availability and safety of reperfusion treatments for stroke.

The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury.

PubMed

Zhang, Qingxiu; Cheng, Hongyu; Rong, Rong; Yang, Hui; Ji, Qiuhong; Li, Qingjie; Rong, Liangqun; Hu, Gang; Xu, Yun

2015-12-01

The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD-93 knockout (PSD-93 KO) mice (C57BL/6 genetic background) and wild-type (WT) littermates were randomly divided into sham and ischemia/reperfusion (I/R) group. The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) suture method. RT-PCR was used to detect the mRNA expression of IL-6, IL-10, Cox-2, iNOS, and TNF-α4h following reperfusion. Infarct volume at different time points after I/R was analyzed using 2,3,5-triphenyl tetrazolium staining, and neurological damage score (neurological severity scores, NSS) was used to evaluate the effect of PSD-93 gene knockout on the MCAO-induced neurological injury. In WT mice, early I/R injury led to the increase in the mRNA expression of proinflammatory cytokines IL-6, Cox-2, iNOS, and TNF-α that coincided with the decrease in the expression of anti-inflammatory cytokine IL-10, as compared to the sham group (P < 0.05). This effect was markedly attenuated by depleting PSD-93 levels by gene knockout. As compared to sham group, in PSD-93 KO mice I/R4h led to downregulation of Cox-2 and iNOS expression, and increase in the mRNA levels of IL-10 (P < 0.05). In addition, following MCAO, PSD-93 KO mice exhibited improved NSS and reduced infarct volumes, as compared with WT animals. PSD-93 knockout may play a neuroprotective role by mediating the early release of inflammatory cytokines induced by cerebral ischemia.

Time-of-Day Dependent Neuronal Injury After Ischemic Stroke: Implication of Circadian Clock Transcriptional Factor Bmal1 and Survival Kinase AKT.

PubMed

Beker, Mustafa Caglar; Caglayan, Berrak; Yalcin, Esra; Caglayan, Ahmet Burak; Turkseven, Seyma; Gurel, Busra; Kelestemur, Taha; Sertel, Elif; Sahin, Zafer; Kutlu, Selim; Kilic, Ulkan; Baykal, Ahmet Tarik; Kilic, Ertugrul

2018-03-01

Occurrence of stroke cases displays a time-of-day variation in human. However, the mechanism linking circadian rhythm to the internal response mechanisms against pathophysiological events after ischemic stroke remained largely unknown. To this end, temporal changes in the susceptibility to ischemia/reperfusion (I/R) injury were investigated in mice in which the ischemic stroke induced at four different Zeitgeber time points with 6-h intervals (ZT0, ZT6, ZT12, and ZT18). Besides infarct volume and brain swelling, neuronal survival, apoptosis, ischemia, and circadian rhythm related proteins were examined using immunohistochemistry, Western blot, planar surface immune assay, and liquid chromatography-mass spectrometry tools. Here, we present evidence that midnight (ZT18; 24:00) I/R injury in mice resulted in significantly improved infarct volume, brain swelling, neurological deficit score, neuronal survival, and decreased apoptotic cell death compared with ischemia induced at other time points, which were associated with increased expressions of circadian proteins Bmal1, PerI, and Clock proteins and survival kinases AKT and Erk-1/2. Moreover, ribosomal protein S6, mTOR, and Bad were also significantly increased, while the levels of PRAS40, negative regulator of AKT and mTOR, and phosphorylated p53 were decreased at this time point compared to ZT0 (06:00). Furthermore, detailed proteomic analysis revealed significantly decreased CSKP, HBB-1/2, and HBA levels, while increased GNAZ, NEGR1, IMPCT, and PDE1B at midnight as compared with early morning. Our results indicate that nighttime I/R injury results in less severe neuronal damage, with increased neuronal survival, increased levels of survival kinases and circadian clock proteins, and also alters the circadian-related proteins.

Association Between Prolonged Seizures and Malignant Middle Cerebral Artery Infarction in Children With Acute Ischemic Stroke.

PubMed

Andrade, Andrea; Bigi, Sandra; Laughlin, Suzanne; Parthasarathy, Sujatha; Sinclair, Adriane; Dirks, Peter; Pontigon, Ann Marie; Moharir, Mahendranath; Askalan, Rand; MacGregor, Daune; deVeber, Gabrielle

2016-11-01

Malignant middle cerebral artery infarct syndrome is a potentially fatal complication of stroke that is poorly understood in children. We studied the frequency, associated characteristics, and outcomes of this condition in children. Children, aged two months to 18 years with acute middle cerebral artery infarct diagnosed at our center between January 2005 and December 2012 were studied. Associations with malignant middle cerebral artery infarct syndrome were sought, including age, seizures, neurological deficit severity (Pediatric National Institute of Health Stroke Severity Score), stroke etiology, fever, blood pressure, blood glucose, infarct location, infarct volume (modified pediatric Alberta Stroke Program Early Computed Tomography Score), and arterial occlusion. Death and neurological outcomes were determined. Among 66 children with middle cerebral artery stroke, 12 (18%) developed malignant middle cerebral artery infarct syndrome, fatal in three. Prolonged seizures during the first 24 hours (odds ratio, 25.51; 95% confidence interval, 3.10 to 334.81; P = 0.005) and a higher Pediatric National Institute of Health Stroke Severity Score (odds ratio, 1.22; 95% confidence interval, 1.08 to 1.45; P = 0.006) were independently associated with malignant middle cerebral artery infarct syndrome. All children aged greater than two years with a Pediatric National Institute of Health Stroke Severity Score ≥8 and initial seizures ≥5 minutes duration developed malignant middle cerebral artery infarct syndrome (100%). Malignant middle cerebral artery infarct syndrome affects nearly one in five children with acute middle cerebral artery stroke. Children with higher Pediatric National Institute of Health Stroke Severity Scores and prolonged initial seizures are at greatly increased risk for malignant middle cerebral artery infarct syndrome. Children with middle cerebral artery infarcts warrant intensive neuroprotective management and close monitoring to enable early referral for hemicraniectomy surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Prospective Evaluation of 18F-Fluorodeoxyglucose Uptake in Postischemic Myocardium by Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging as a Prognostic Marker of Functional Outcome.

PubMed

Rischpler, Christoph; Dirschinger, Ralf J; Nekolla, Stephan G; Kossmann, Hans; Nicolosi, Stefania; Hanus, Franziska; van Marwick, Sandra; Kunze, Karl P; Meinicke, Alexander; Götze, Katharina; Kastrati, Adnan; Langwieser, Nicolas; Ibrahim, Tareq; Nahrendorf, Matthias; Schwaiger, Markus; Laugwitz, Karl-Ludwig

2016-04-01

The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI (18)F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of (18)F-FDG positron emission tomography/magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. We prospectively enrolled 49 patients with ST-segment-elevation myocardial infarction and performed (18)F-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, (99m)Tc-sestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of (18)F-FDG-uptake and late gadolinium enhancement showed substantial overlap (κ=0.66), whereas quantitative analysis demonstrated that (18)F-FDG extent exceeded late gadolinium enhancement extent (33.2±16.2% left ventricular myocardium versus 20.4±10.6% left ventricular myocardium, P<0.0001) and corresponded to the area at risk (r=0.87, P<0.0001). The peripheral blood count of CD14(high)/CD16(+) monocytes correlated with the infarction size and (18)F-FDG signal extent (r=0.53, P<0.002 and r=0.42, P<0.02, respectively). (18)F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar, and the standardized uptake valuemean was associated with left ventricular functional outcome independent of infarct size (Δ ejection fraction: P<0.04, Δ end-diastolic volume: P<0.02, Δ end-systolic volume: P<0.005). In this study, the intensity of (18)F-FDG uptake in the myocardium after acute myocardial infarction correlated inversely with functional outcome at 6 months. Thus, (18)F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury. © 2016 American Heart Association, Inc.

Variations in the use of emergency PCI for the treatment of re-infarction following intravenous fibrinolytic therapy: impact on outcomes in HERO-2.

PubMed

Edmond, J J; French, J K; Aylward, P E G; Wong, C K; Stewart, R A H; Williams, B F; De Pasquale, C G; O'connell, R L; Van den Berg, K; Van de Werf, F J; Simes, R J; White, H D

2007-06-01

Patients who suffer re-infarction during initial hospitalization for ST-elevation myocardial infarction (STEMI) have decreased survival compared to patients without re-infarction, so treatment of re-infarction may influence survival. To determine whether the utilization of reperfusion therapies varied within 12 h of re-infarction and was associated with 30-day mortality, we studied 552 patients with re-infarction of 17,073 patients with STEMI enrolled in HERO-2 in five regions (Russia, Eastern Europe, Western Countries, Asia, and Latin America). Patients presenting within 6 h of symptom-onset were randomized to receive either bivalirudin or unfractionated heparin intravenously just prior to streptokinase. Re-infarction occurred in 2.8 and 3.6% of bivalirudin and heparin treated patients, respectively (P = 0.004), but treatment assignment did not influence mortality after re-infarction. Patients with re-infarction had a higher 30-day mortality than those without re-infarction (24 vs. 10%; P < 0.001 by Cox model). Within 12 h of re-infarction, fibrinolytic therapy was administered to 12.0 and 8.2% underwent percutaneous coronary intervention (PCI); these two treatments were more frequently utilized in patients from Western countries (n = 112), compared to patients from other countries (n = 440) (34.8 and 16.1% compared to 6.1 and 6.1%, respectively, P < 0.001). Mortality was 15% in patients receiving reperfusion therapy for re-infarction and 27% for those with conservative management, hazard ratio (HR) 0.53 (95% CI 0.32-0.88), P = 0.01. In multiple Cox regression analysis which included adjustment for clinical variables and randomized treatment assignment, 30-day mortality after re-infarction varied by region (highest Latin America 29%, lowest Western countries 15%; P = 0.01). Other independent prognostic factors included age, time from randomization to re-infarction, and Killip class at randomization. The HR for PCI treatment of re-infarction was 0.18 [(95% CI 0.04-0.76), P = 0.02] in analyses which excluded deaths within 12 h. Treatment of re-infarction with reperfusion therapies was markedly under-utilized, especially in non-western countries. PCI for re-infarction, in particular, was associated with a lower 30-day mortality, which may reflect both patient selection and effects of treatment.

SERIAL ULTRASOUND EVALUATION OF INTRAMYOCARDIAL STRAIN AFTER REPERFUSED MYOCARDIAL INFARCTION REVEALS THAT REMOTE ZONE DYSSYNCHRONY DEVELOPS IN CONCERT WITH LEFT VENTRICULAR REMODELING

PubMed Central

Li, Yinbo; Garson, Christopher D.; Xu, Yaqin; Helm, Patrick A.; Hossack, John A.; French, Brent A.

2011-01-01

This study noninvasively evaluated the development of left ventricular (LV) dyssynchrony following reperfused myocardial infarction (MI) in mice using an ultrasonic speckle-tracking method. Eight C57BL/6J mice were assessed by high-resolution echocardiography at baseline and at eight time-points following MI. Images were acquired at 1mm elevational intervals encompassing the entire LV to determine chamber volumes and radial strain. Receiver-operating characteristic (ROC) analysis of regional radial strain was used to segment the three-dimensional (3-D) LV into infarct, adjacent and remote zones. This in vivo segmentation was correlated to histologic infarct size (R = 0.89, p < 0.01) in a short-axis, slice-by-slice comparison. The onset of dyssynchrony during LV remodeling was assessed by standard deviation of time to peak radial strain in the infarct, adjacent and remote zones. It was discovered that the form of LV dyssynchrony that develops in the remote zone late after MI does so in concert with the progression of LV remodeling (R = 0.70, p < 0.05). PMID:21640480

Determinants of the distribution and severity of hypoperfusion in patients with ischemic stroke.

PubMed

Bang, O Y; Saver, J L; Alger, J R; Starkman, S; Ovbiagele, B; Liebeskind, D S

2008-11-25

In acute cerebral ischemia, two variables characterize the extent of hypoperfusion: the volume of hypoperfused tissue and the intensity of hypoperfusion within these regions. We evaluated the determinants of the intensity of hypoperfusion within oligemic regions among patients who were eligible for recanalization therapy for acute ischemic stroke. We analyzed data, including pretreatment diffusion-weighted imaging (DWI) and perfusion-weighted imaging, on 119 patients with acute middle cerebral artery infarctions. The intensity of hypoperfusion within oligemic regions was characterized by the hypoperfusion intensity ratio (HIR), defined as the volume of tissue with severe hypoperfusion (Tmax > or = 8 seconds) divided by the volume of tissue with any hypoperfusion (Tmax > or = 2 seconds). Based on the DWI data, we divided the patients into four stroke phenotypes: large cortical, small (< 1 cm diameter) cortical, border-zone, and deep pattern. The mean (SD) volume of severe hypoperfusion was 54.6 (52.5) mL, and that of any hypoperfusion was 140.8 (81.3) mL. The HIR ranged widely, from 0.002 to 0.974, with a median of 0.35 (interquartile range 0.13-0.60). The volume of any hypoperfusion did not predict the intensity of hypoperfusion within the affected region (r = 0.10, p = 0.284). Angiographic collateral flow grade was associated with HIRs (p value for trend = 0.019) and differed among DWI lesion patterns. In multivariate analysis, diastolic pressure on admission (odds ratio 0.959, 95% CI 0.922-0.998) and DWI pattern of deep infarcts (odds ratio 18.004 compared with large cortical pattern, 95% CI 1.855-173.807) were independently associated with a low HIR. The intensity of hypoperfusion within an oligemic field is largely independent of the size of the oligemia region. Predictors of lesser intensity of hypoperfusion are lower diastolic blood pressure and presence of a deep diffusion-weighted imaging lesion pattern.

A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology.

PubMed

Alosco, Michael L; Sugarman, Michael A; Besser, Lilah M; Tripodis, Yorghos; Martin, Brett; Palmisano, Joseph N; Kowall, Neil W; Au, Rhoda; Mez, Jesse; DeCarli, Charles; Stein, Thor D; McKee, Ann C; Killiany, Ronald J; Stern, Robert A

2018-01-01

White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been postulated to be a core feature of Alzheimer's disease. Clinicopathological studies are needed to elucidate and confirm this possibility. This study examined: 1) the association between antemortem WMH and autopsy-confirmed Alzheimer's disease neuropathology (ADNP), 2) the relationship between WMH and dementia in participants with ADNP, and 3) the relationships among cerebrovascular disease, WMH, and ADNP. The sample included 82 participants from the National Alzheimer's Coordinating Center's Data Sets who had quantitated volume of WMH from antemortem FLAIR MRI and available neuropathological data. The Clinical Dementia Rating (CDR) scale (from MRI visit) operationalized dementia status. ADNP+ was defined by moderate to frequent neuritic plaques and Braak stage III-VI at autopsy. Cerebrovascular disease neuropathology included infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy. 60/82 participants were ADNP+. Greater volume of WMH predicted increased odds for ADNP (p = 0.037). In ADNP+ participants, greater WMH corresponded with increased odds for dementia (CDR≥1; p = 0.038). WMH predicted cerebral amyloid angiopathy, microinfarcts, infarcts, and lacunes (ps < 0.04). ADNP+ participants were more likely to have moderate-severe arteriolosclerosis and cerebral amyloid angiopathy compared to ADNP-participants (ps < 0.04). This study found a direct association between total volume of WMH and increased odds for having ADNP. In patients with Alzheimer's disease, FLAIR MRI WMH may be able to provide key insight into disease severity and progression. The association between WMH and ADNP may be explained by underlying cerebrovascular disease.

[An evaluation of clinical characteristics and prognosis of brain-stem infarction in diabetics].

PubMed

Lu, Zheng-qi; Li, Hai-yan; Hu, Xue-qiang; Zhang, Bing-jun

2011-01-01

To analyze the relationship between diabetics and the onset, clinical outcomes and prognosis of brainstem infarction, and to evaluate the impact of diabetes on brainstem infarction. Compare 172 cases of acute brainstem infarction in patients with or without diabetes. Analyze the associated risk factors of patients with brain-stem infarction in diabetics by multi-variate logistic regression analysis. Compare the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin scale (mRS) Score, pathogenetic condition and the outcome of the two groups in different times. The systolic blood pressure (SBP), TG, LDL-C, apolipoprotein B (Apo B), glutamyl transpeptidase (γ-GT), fibrinogen (Fb), fasting blood glucose (FPG) and glycosylated hemoglobin(HbA1c)in diabetic group were higher than those in non-diabetic group, which was statistically significant (P < 0.05). From multi-variate logistic regression analysis, γ-GT, Apo B and FPG were the risk predictors of diabetes with brainstem infarction(OR = 1.017, 4.667 and 3.173, respectively), while HDL-C was protective (OR = 0.288). HbA1c was a risk predictor of severity for acute brainstem infarction (OR = 1.299), while Apo A was beneficial (OR = 0.212). Compared with brain-stem infarction in non-diabetic group, NIHSS score and intensive care therapy of diabetic groups on the admission had no statistically significance, while the NIHSS score on discharge and the outcome at 6 months' of follow-up were statistically significant. Diabetes is closely associated with brainstem infarction. Brainstem infarction with diabetes cause more rapid progression, poorer prognosis, higher rates of mortality as well as disability and higher recurrence rate of cerebral infarction.

Comparison of neointimal hyperplasia with drug-eluting stents versus bare metal stents in patients undergoing intracoronary bone-marrow mononuclear cell transplantation following acute myocardial infarction.

PubMed

Villa, Adolfo; Arnold, Roman; Sánchez, Pedro L; Gimeno, Federico; Ramos, Benigno; Cantero, Teresa; Fernández, Maria Eugenia; Sanz, Ricardo; Gutiérrez, Oliver; Mota, Pedro; García-Frade, Javier; San Román, José Alberto; Fernández-Avilés, Francisco

2009-06-15

The aims of this study were to assess the safety of drug-eluting stent (DES) use and to compare the incidence of in-stent restenosis (ISR) and neointimal hyperplasia formation according to the type of stent implanted (DES vs bare-metal stents [BMS]) in patients who underwent intracoronary bone marrow mononuclear cell transplantation after acute ST elevation myocardial infarction. Fifty-nine patients with successfully revascularized ST elevation myocardial infarction (37 using BMS and 22 using DES) underwent paired angiographic examinations at baseline and 6 to 9 months after the intracoronary injection of 91 million +/- 56 million autologous bone marrow mononuclear cells. A subgroup of 30 patients also underwent serial intravascular ultrasound examinations. Off-line angiographic assessment showed 4 cases of binary ISR, primarily in BMS (3 cases), and no major adverse cardiac events were associated with stent type (mean follow-up period 41 +/- 10 months). At follow-up, angiographic late luminal loss was significantly lower in patients with DES than in those patients with BMS (0.35 +/- 0.66 vs 0.71 +/- 0.38 mm, p = 0.011). Multivariate analysis identified the use of DES (beta = -0.32, 95% confidence interval [CI] -0.57 to -0.26, p = 0.03) and a smaller baseline reference vessel diameter (beta = 0.29, 95% CI 0.04 to 0.54, p = 0.02) as independent predictors of lower late loss. Moreover, intravascular ultrasound showed a significant reduction of in-stent neointimal hyperplasia formation related to DES use compared with BMS use (Delta neointimal hyperplasia volume 5.4 mm(3) [95% CI 2.7 to 28.1] vs 35.9 mm(3) [95% CI 22.0 to 43.6], p = 0.035). In conclusion, these findings suggest that the use of DES is safe and may prevent ISR and neointimal hyperplasia formation in patients who undergo intracoronary bone marrow mononuclear cell transplantation after a successfully revascularized ST elevation myocardial infarction.

Prognostic significance of infarct core pathology revealed by quantitative non-contrast in comparison with contrast cardiac magnetic resonance imaging in reperfused ST-elevation myocardial infarction survivors.

PubMed

Carrick, David; Haig, Caroline; Rauhalammi, Sam; Ahmed, Nadeem; Mordi, Ify; McEntegart, Margaret; Petrie, Mark C; Eteiba, Hany; Hood, Stuart; Watkins, Stuart; Lindsay, Mitchell; Mahrous, Ahmed; Ford, Ian; Tzemos, Niko; Sattar, Naveed; Welsh, Paul; Radjenovic, Aleksandra; Oldroyd, Keith G; Berry, Colin

2016-04-01

To assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI). We performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (mean ± SD age 59 ± 12 years, 74% male) who underwent CMR 2 days and 6 months post-myocardial infarction (n = 267). Native T1 was measured in myocardial regions of interest (n = 288). Adverse remodelling was defined as an increase in left ventricular (LV) end-diastolic volume ≥20% at 6 months. All-cause death or first heart failure hospitalization was a pre-specified outcome that was assessed during follow-up (median duration 845 days). One hundred and sixty (56%) patients had a hypo-intense infarct core disclosed by native T1. In multivariable regression, infarct core native T1 was inversely associated with adverse remodelling [odds ratio (95% confidence interval (CI)] per 10 ms reduction in native T1: 0.91 (0.82, 0.00); P = 0.061). Thirty (10.4%) of 288 patients died or experienced a heart failure event and 13 of these events occurred post-discharge. Native T1 values (ms) within the hypo-intense infarct core (n = 160 STEMI patients) were inversely associated with the risk of all-cause death or first hospitalization for heart failure post-discharge (for a 10 ms increase in native T1: hazard ratio 0.730, 95% CI 0.617, 0.863; P < 0.001) including after adjustment for left ventricular ejection fraction, infarct core T2 and myocardial haemorrhage. The prognostic results for microvascular obstruction were similar. Infarct core native T1 represents a novel non-contrast CMR biomarker with potential for infarct characterization and prognostication in STEMI survivors. Confirmatory studies are warranted. CLINICALTRIALS. NCT02072850. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Patent Foramen Ovale in Patients with Cerebral Infarction: A Transesophageal Echocradigraphy Study

NASA Technical Reports Server (NTRS)

Petty, George W.; Khandheria, Bijoy K.; Chu, Chu-Pin; Sicks, JoRean D.; Whisnant, Jack P.

1997-01-01

Patent foramen ovale was detected in 37 patients (32%). Mean age was similar in those with (60 years) and those without (64 years) PFO. Patent foramen ovale was more frequent among men (39%) than women (20%, P=.03). Patients with PFO had a lower frequency of atrial fibrillation, diabetes me!litus, hypertension, and peripheral vascular disease compared with those without PFO. There was no difference in frequency of the following characteristics in patients with PFO compared with those without PFO: pulmonary embolus, chronic obstructive pulmonary disease, pulmonary hypertension, peripheral embolism, prior cerebral infarction, nosocomial cerebral infarction, Valsalva maneuver at the time of cerebral infarction, recent surgery, or hemorrhagic transformation of cerebral infarction. Patent foramen ovale was found in 22 (40%) of 55 patients with infarcts of uncertain cause and in 15 (25%) of 61 with infarcts of known cause (cardioembolic, 21%; large vessel atherostenosis, 25%; lacune, 40%) (P=.08). When the analysis was restricted to patients who underwent Valsalva maneuver, PFO with right to left or bidirectional shunt was found in 19 (50%) of 38 patients with infarcts of uncertain cause and in 6 (20%) of 30 with infarcts of known cause (P=.Ol). Conclusion: Although PFO was over-represented in patients with infarcts of uncertain cause in our and other studies, it has a high frequency among patients with cerebral infarction of all types. The relation between PFO and stroke requires further study.

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct.

PubMed

Nogueira, Raul G; Jadhav, Ashutosh P; Haussen, Diogo C; Bonafe, Alain; Budzik, Ronald F; Bhuva, Parita; Yavagal, Dileep R; Ribo, Marc; Cognard, Christophe; Hanel, Ricardo A; Sila, Cathy A; Hassan, Ameer E; Millan, Monica; Levy, Elad I; Mitchell, Peter; Chen, Michael; English, Joey D; Shah, Qaisar A; Silver, Frank L; Pereira, Vitor M; Mehta, Brijesh P; Baxter, Blaise W; Abraham, Michael G; Cardona, Pedro; Veznedaroglu, Erol; Hellinger, Frank R; Feng, Lei; Kirmani, Jawad F; Lopes, Demetrius K; Jankowitz, Brian T; Frankel, Michael R; Costalat, Vincent; Vora, Nirav A; Yoo, Albert J; Malik, Amer M; Furlan, Anthony J; Rubiera, Marta; Aghaebrahim, Amin; Olivot, Jean-Marc; Tekle, Wondwossen G; Shields, Ryan; Graves, Todd; Lewis, Roger J; Smith, Wade S; Liebeskind, David S; Saver, Jeffrey L; Jovin, Tudor G

2018-01-04

The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00). Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).

Structural MRI markers of brain aging early after ischemic stroke.

PubMed

Werden, Emilio; Cumming, Toby; Li, Qi; Bird, Laura; Veldsman, Michele; Pardoe, Heath R; Jackson, Graeme; Donnan, Geoffrey A; Brodtmann, Amy

2017-07-11

To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. First-ever stroke was associated with smaller hippocampal volume ( p = 0.025) and greater WMH volume ( p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke ( p = 0.017) and controls ( p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls ( p = 0.056), but the association became significant after further adjustment for atrial fibrillation ( p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction.

PubMed

Yoon, Young-Sup; Park, Jong-Seon; Tkebuchava, Tengiz; Luedeman, Corinne; Losordo, Douglas W

2004-06-29

There has been a rapid increase in the number of clinical trials using unselected bone marrow (BM) cells or the mononuclear fraction of BM cells for treating ischemic heart diseases. Thus far, no significant deleterious effects or complications have been reported in any studies using BM-derived cells for treatment of various cardiac diseases. Seven-week-old female Fisher-344 rats underwent surgery to induce acute myocardial infarction and were randomized into 3 groups of 16 rats, each receiving intramyocardial injection of either 7x10(5) DiI-labeled total BM cells (TBMCs), the same number of DiI-labeled, clonally expanded BM multipotent stem cells, or the same volume of phosphate-buffered saline in the peri-infarct area. Echocardiography 2 weeks after cell transplantation indicated intramyocardial calcification in 4 of 14 surviving rats (28.5%) in the TBMC group. Histological examination with hematoxylin and eosin staining and von Kossa staining confirmed the presence of extensive intramyocardial calcification. Alkaline phosphatase staining revealed strong positivity surrounding the calcified area suggestive of ongoing osteogenic activity. Fluorescent microscopic examination revealed that acellular calcific areas were surrounded by DiI-labeled TBMCs, suggesting the direct involvement of transplanted TBMCs in myocardial calcification. In contrast, in hearts receiving equal volumes of saline or BM multipotent stem cells delivered in the same manner, there was no evidence of calcification. These results demonstrate that direct transplantation of unselected BM cells into the acutely infarcted myocardium may induce significant intramyocardial calcification.

Injectable Microsphere Gel Progressively Improves Global Ventricular Function, Regional Contractile Strain, and Mitral Regurgitation after Myocardial Infarction

PubMed Central

McGarvey, Jeremy R; Kondo, Norihiro; Witschey, Walter RT; Takebe, Manabu; Aoki, Chikashi; Burdick, Jason A.; Spinale, Francis G; Gorman, Joseph H; Pilla, James J; Gorman, Robert C

2014-01-01

Background There is continued need for therapies which reverse or abate the remodeling process following myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model. Methods Twenty five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into four groups: one week treatment, one week control, four week treatment, and four week control. Following infarction, animals received either twenty 150μl calcium hydroxyapatite gel or saline injections within the infarct. At their respective timepoints, echocardiograms, cardiac MRI, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content. Results Global and regional LV function were depressed in all infarcted subjects at one week compared to healthy controls. By four weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared to infarcted controls (EF 48.5±1.9% vs. 38.0±1.7%, p<0.01). Similarly, regional borderzone radial contractile strain (16.3±1.5% vs. 11.2±1.5%, p=0.04), MR grade (0.4±0.2 vs. 1.2±0.2, p=0.04), and infarct thickness (7.8±0.5mm vs. 4.5±0.2mm, p<0.01) were improved at this timepoint in the treatment group compared to infarct controls. Conclusions Calcium hydroxyapatite injection following MI progressively improves global LV function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is viable alternative in the current management of heart failure. PMID:25524397

Cardiac magnetic resonance based evaluation of aortic stiffness and epicardial fat volume in patients with hypertension, diabetes mellitus, and myocardial infarction.

PubMed

Homsi, Rami; Sprinkart, Alois M; Gieseke, Juergen; Meier-Schroers, Michael; Yuecel, Seyrani; Fischer, Stefan; Nadal, Jennifer; Dabir, Darius; Luetkens, Julian A; Kuetting, Daniel L; Schild, Hans H; Thomas, Daniel K

2018-01-01

Background Aortic stiffness and epicardial fat relate to cardiovascular risk. Their relationship with each other and their role with hypertension, diabetes mellitus (DM), and myocardial infarction (MI) can be evaluated by cardiac magnetic resonance (CMR). Purpose To explore an association between aortic stiffness and epicardial as well as paracardial fat volume (EFV and ParaFV, respectively) in hypertensive patients and to relate the results to the presence of DM and MI. Material and Methods A total of 156 hypertensive and 20 non-hypertensive participants were examined at 1.5 Tesla. A 2D-velocity-encoded sequence was acquired to assess aortic pulse wave velocity (PWV in m/s) as a measure of aortic stiffness. A 3D-Dixon sequence was used to determine EFV and ParaFV. Results PWV correlated with EFV (R = 0.474; P < 0.001), but not with ParaFV. Fat volumes (in mL/m 2 ) and PWV were lower in non-hypertensive controls compared to hypertensive patients. EFV and PWV were significantly higher in diabetic hypertensive patients without MI (n = 19; PWV: 10.4 ± 2.9; EFV: 92.5 ± 19.3) compared to hypertension-only patients (n = 84 [no DM or MI]; EFV: 64.8 ± 25.1, PWV: 9.0 ± 2.6; P < 0.05). Logistic regression analysis showed a significant association between the presence of a MI and a higher EFV ( P < 0.05), but not with PWV ( P = 0.060) or ParaFV ( P = 0.375). Conclusion A relationship between aortic stiffness and EFV was found in hypertensive patients. Both were increased in the presence of DM; however, only EFV was increased in the presence of MI. This may relate to the PWV lowering effect of the antihypertensive medication used by hypertensive patients and underscores the benefit of EFV assessment in this regard.

Delayed administration of parecoxib, a specific COX-2 inhibitor, attenuated postischemic neuronal apoptosis by phosphorylation Akt and GSK-3β.

PubMed

Ye, Zhi; Wang, Na; Xia, Pingping; Wang, E; Yuan, Yajing; Guo, Qulian

2012-02-01

Parecoxib is a recently described novel COX-2 inhibitor whose functional significance and neuroprotective mechanisms remain elusive. Therefore, in this study, we aimed to investigate whether delayed administration of parecoxib inhibited mitochondria-mediated neuronal apoptosis induced by ischemic reperfusion injury via phosphorylating Akt and its downstream target protein, glycogen synthase kinase 3β (GSK-3β). Adult male Sprague-Dawley rats were administered parecoxib (10 or 30 mg kg(-1), IP) or isotonic saline twice a day starting 24 h after middle cerebral artery occlusion (MCAO) for three consecutive days. Cerebral infarct volume, apoptotic neuron, caspase-3 immunoreactivity and the protein expression of p-Akt, p-GSK-3β and Cytochrome C in cerebral ischemic cortex were evaluated at 96 h after reperfusion. Parecoxib significantly diminished infarct volume and attenuated neuron apoptosis in a dose-independent manner, compared with MCAO group alone. Increased p-Akt and p-GSK-3β was observed in the ischemic penumbra of parecoxib group after stroke. Moreover, parecoxib also reduced the release of Cytochrome C from mitochondrial into cytosol and attenuated the caspase-3 immunoreactivity in the penumbra. Taken together, these results suggested that parecoxib ameliorated postischemic mitochondria-mediated neuronal apoptosis induced by focal cerebral ischemia in rats and this neuroprotective potential is involved in phosphorylation of Akt and GSK-3β.

Comparison of the anti-apoptotic effects of 15- and 35-minute suspended moxibustion after focal cerebral ischemia/reperfusion injury.

PubMed

Xiao, Ai-Jiao; He, Lin; Ouyang, Xin; Liu, Jie-Min; Chen, Ming-Ren

2018-02-01

Heat-sensitive suspended moxibustion has a neuroprotective effect against focal cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. The duration of heat-sensitive suspended moxibustion (usually from 30 minutes to 1 hour) is longer than traditional suspended moxibustion (usually 15 minutes). However, the effects of 15- and 35-minute suspended moxibustion in rats with cerebral ischemia/reperfusion injury are poorly understood. In this study, we performed 15- or 35-minute suspended moxibustion at acupoint Dazhui (GV14) in an adult rat model of focal cerebral ischemia/reperfusion injury. Infarct volume was evaluated with the 2,3,5-triphenyltetrazolium chloride assay. Histopathological changes and neuronal apoptosis at the injury site were assessed by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Caspase-9 and caspase-3 expression at the injury site was detected using immunofluorescent staining. Bax and Bcl-2 expression at the injury site was assessed using western blot assay. In the 35-minute moxibustion group, infarct volume was decreased, neuronal apoptosis was reduced, caspase-9, caspase-3 and Bax expression was lower, and Bcl-2 expression was increased, compared with the 15-minute moxibustion group. Our findings show that 35-minute moxibustion has a greater anti-apoptotic effect than 15-minute moxibustion after focal cerebral ischemia/reperfusion injury.

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment.

PubMed

Padroni, Marina; Bernardoni, Andrea; Tamborino, Carmine; Roversi, Gloria; Borrelli, Massimo; Saletti, Andrea; De Vito, Alessandro; Azzini, Cristiano; Borgatti, Luca; Marcello, Onofrio; d'Esterre, Christopher; Ceruti, Stefano; Casetta, Ilaria; Lee, Ting-Yim; Fainardi, Enrico

2016-01-01

The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS ≤ 2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment

PubMed Central

Padroni, Marina; Bernardoni, Andrea; Tamborino, Carmine; Roversi, Gloria; Borrelli, Massimo; Saletti, Andrea; De Vito, Alessandro; Azzini, Cristiano; Borgatti, Luca; Marcello, Onofrio; d’Esterre, Christopher; Ceruti, Stefano; Casetta, Ilaria; Lee, Ting-Yim; Fainardi, Enrico

2016-01-01

Introduction The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. Methods 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. Results Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. Conclusions Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size. PMID:26824672

Diabetes increases mortality after myocardial infarction by oxidizing CaMKII

PubMed Central

Luo, Min; Guan, Xiaoqun; Luczak, Elizabeth D.; Lang, Di; Kutschke, William; Gao, Zhan; Yang, Jinying; Glynn, Patric; Sossalla, Samuel; Swaminathan, Paari D.; Weiss, Robert M.; Yang, Baoli; Rokita, Adam G.; Maier, Lars S.; Efimov, Igor R.; Hund, Thomas J.; Anderson, Mark E.

2013-01-01

Diabetes increases oxidant stress and doubles the risk of dying after myocardial infarction, but the mechanisms underlying increased mortality are unknown. Mice with streptozotocin-induced diabetes developed profound heart rate slowing and doubled mortality compared with controls after myocardial infarction. Oxidized Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic patients compared with that in nondiabetic patients after myocardial infarction. Streptozotocin-treated mice had increased pacemaker cell ox-CaMKII and apoptosis, which were further enhanced by myocardial infarction. We developed a knockin mouse model of oxidation-resistant CaMKIIδ (MM-VV), the isoform associated with cardiovascular disease. Streptozotocin-treated MM-VV mice and WT mice infused with MitoTEMPO, a mitochondrial targeted antioxidant, expressed significantly less ox-CaMKII, exhibited increased pacemaker cell survival, maintained normal heart rates, and were resistant to diabetes-attributable mortality after myocardial infarction. Our findings suggest that activation of a mitochondrial/ox-CaMKII pathway contributes to increased sudden death in diabetic patients after myocardial infarction. PMID:23426181

Cardiovascular progenitor-derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure.

PubMed

Kervadec, Anaïs; Bellamy, Valérie; El Harane, Nadia; Arakélian, Lousineh; Vanneaux, Valérie; Cacciapuoti, Isabelle; Nemetalla, Hany; Périer, Marie-Cécile; Toeg, Hadi D; Richart, Adèle; Lemitre, Mathilde; Yin, Min; Loyer, Xavier; Larghero, Jérôme; Hagège, Albert; Ruel, Marc; Boulanger, Chantal M; Silvestre, Jean-Sébastien; Menasché, Philippe; Renault, Nisa K E

2016-06-01

Cell-based therapies are being explored as a therapeutic option for patients with chronic heart failure following myocardial infarction. Extracellular vesicles (EV), including exosomes and microparticles, secreted by transplanted cells may orchestrate their paracrine therapeutic effects. We assessed whether post-infarction administration of EV released by human embryonic stem cell-derived cardiovascular progenitors (hESC-Pg) can provide equivalent benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate similar endogenous pathways. Mice underwent surgical occlusion of their left coronary arteries. After 2-3 weeks, 95 mice included in the study were treated with hESC-Pg, EV, or Minimal Essential Medium Alpha Medium (alpha-MEM; vehicle control) delivered by percutaneous injections under echocardiographic guidance into the peri-infarct myocardium. functional and histologic end-points were blindly assessed 6 weeks later, and hearts were processed for gene profiling. Genes differentially expressed between control hearts and hESC-Pg-treated and EV-treated hearts were clustered into functionally relevant pathways. At 6 weeks after hESC-Pg administration, treated mice had significantly reduced left ventricular end-systolic (-4.20 ± 0.96 µl or -7.5%, p = 0.0007) and end-diastolic (-4.48 ± 1.47 µl or -4.4%, p = 0.009) volumes compared with baseline values despite the absence of any transplanted hESC-Pg or human embryonic stem cell-derived cardiomyocytes in the treated mouse hearts. Equal benefits were seen with the injection of hESC-Pg-derived EV, whereas animals injected with alpha-MEM (vehicle control) did not improve significantly. Histologic examination suggested a slight reduction in infarct size in hESC-Pg-treated animals and EV-treated animals compared with alpha-MEM-treated control animals. In the hESC-Pg-treated and EV-treated groups, heart gene profiling identified 927 genes that were similarly upregulated compared with the control group. Among the 49 enriched pathways associated with these up-regulated genes that could be related to cardiac function or regeneration, 78% were predicted to improve cardiac function through increased cell survival and/or proliferation or DNA repair as well as pathways related to decreased fibrosis and heart failure. In this post-infarct heart failure model, either hESC-Pg or their secreted EV enhance recovery of cardiac function and similarly affect cardiac gene expression patterns that could be related to this recovery. Although the mechanisms by which EV improve cardiac function remain to be determined, these results support the idea that a paracrine mechanism is sufficient to effect functional recovery in cell-based therapies for post-infarction-related chronic heart failure. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Synergistic cardioprotective effects of rAAV9-CyclinA2 combined with fibrin glue in rats after myocardial infarction.

PubMed

Cao, Wen; Chang, Ya-Fei; Zhao, Ai-Chao; Chen, Bang-Dang; Liu, Fen; Ma, Yi-Tong; Ma, Xiang

2017-08-01

The present study aimed to investigate the protective effects of rAAV9-CyclinA2 combined with fibrin glue (FG) in vivo in rats after myocardial infarction (MI). Ninety male Sprague-Dawley rats were randomized into 6 groups (15 in each group): sham, MI, rAAV9-green fluorescent protein (GFP) + MI, rAAV9-CyclinA2 + MI, FG + MI, and rAAV9-CyclinA2 + FG + MI. Packed virus (5 × 10 11 vg/ml) in 150 µl of normal saline or FG was injected into the infarcted myocardium at five locations in rAAV9-GFP + MI, rAAV9-CyclinA2 + MI, and rAAV9-CyclinA2 + FG + MI groups. The sham, MI, and FG + MI groups were injected with an equal volume of normal saline or FG at the same sites. Five weeks after injection, echocardiography was performed to evaluate the left ventricular function. The expressions of CyclinA2, proliferating cell nuclear antigen (PCNA), and phospho-histone-H3 (H3P), vascular density, and infarct area were assessed by Western blot, immunohistochemistry, immunofluorescence, and Masson staining. As a result, the combination of rAAV9-CyclinA2 and FG increased ejection fraction and fractional shortening compared with FG or rAAV9-CyclinA2 alone. The expression level of CyclinA2 was significantly higher in the rAAV9-CyclinA2 + FG + MI group compared with the rAAV9-CyclinA2 + MI and FG + MI groups (70.1 ± 1.86% vs. 14.74 ± 2.02%, P < 0.01; or vs. 50.13 ± 3.80%; P < 0.01). A higher expression level of PCNA and H3P was found in the rAAV9-CyclinA2 + FG + MI group compared with other groups. Comparing with other experiment groups, collagen deposition and the infarct size significantly decreased in rAAV9-CyclinA2 + Fibrin + MI group. The vascular density was much higher in the rAAV9-CyclinA2 + FG + MI group compared with the rAAV9-CyclinA2 + MI group. We concluded that fibrin glue combined with rAAV9-CyclinA2 was found to be effective in cardiac remodeling and improving myocardial protection.

Effects of myocardial infarction on the distribution and transport of nutrients and oxygen in porcine myocardium.

PubMed

Davis, Bryce H; Morimoto, Yoshihisa; Sample, Chris; Olbrich, Kevin; Leddy, Holly A; Guilak, Farshid; Taylor, Doris A

2012-10-01

One of the primary limitations of cell therapy for myocardial infarction is the low survival of transplanted cells, with a loss of up to 80% of cells within 3 days of delivery. The aims of this study were to investigate the distribution of nutrients and oxygen in infarcted myocardium and to quantify how macromolecular transport properties might affect cell survival. Transmural myocardial infarction was created by controlled cryoablation in pigs. At 30 days post-infarction, oxygen and metabolite levels were measured in the peripheral skeletal muscle, normal myocardium, the infarct border zone, and the infarct interior. The diffusion coefficients of fluorescein or FITC-labeled dextran (0.3-70 kD) were measured in these tissues using fluorescence recovery after photobleaching. The vascular density was measured via endogenous alkaline phosphatase staining. To examine the influence of these infarct conditions on cells therapeutically used in vivo, skeletal myoblast survival and differentiation were studied in vitro under the oxygen and glucose concentrations measured in the infarct tissue. Glucose and oxygen concentrations, along with vascular density were significantly reduced in infarct when compared to the uninjured myocardium and infarct border zone, although the degree of decrease differed. The diffusivity of molecules smaller than 40 kD was significantly higher in infarct center and border zone as compared to uninjured heart. Skeletal myoblast differentiation and survival were decreased stepwise from control to hypoxia, starvation, and ischemia conditions. Although oxygen, glucose, and vascular density were significantly reduced in infarcted myocardium, the rate of macromolecular diffusion was significantly increased, suggesting that diffusive transport may not be inhibited in infarct tissue, and thus the supply of nutrients to transplanted cells may be possible. in vitro studies mimicking infarct conditions suggest that increasing nutrients available to transplanted cells may significantly increase their ability to survive in infarct.

Axial diffusivity changes in the motor pathway above stroke foci and functional recovery after subcortical infarction.

PubMed

Liu, Gang; Peng, Kangqiang; Dang, Chao; Tan, Shuangquan; Chen, Hongbing; Xie, Chuanmiao; Xing, Shihui; Zeng, Jinsheng

2018-01-01

Secondary degeneration of the fiber tract of the motor pathway below infarct foci and functional recovery after stroke have been well demonstrated, but the role of the fiber tract above stroke foci remains unclear. This study aimed to investigate diffusion changes in motor fibers above the lesion and identify predictors of motor improvement within 12 weeks after subcortical infarction. Diffusion tensor imaging and the Fugl-Meyer (FM) scale were conducted 1, 4, and 12 weeks (W) after a subcortical infarct. Proportional recovery model residuals were used to assign patients to proportional recovery and poor recovery groups. Region of interest analysis was used to assess diffusion changes in the motor pathway above and below a stroke lesion. Multivariable linear regression was employed to identify predictors of motor improvement within 12 weeks after stroke. Axial diffusivity (AD) in the underlying white matter of the ipsilesional primary motor area (PMA) and cerebral peduncle (CP) in both proportional and poor recovery groups was lower at W1 compared to the controls and values in the contralesional PMA and CP (all P < 0.05). Subsequently, AD in the ipsilesional CP became relatively stable, while AD in the ipsilesional PMA significantly increased from W4 to W12 after stroke (P < 0.05). In all of the patients, changes in the FM scores were greater in those with higher changes in AD of the ipsilesional PMA. Only initial impairment or lesion volume was predictive of motor improvement within 12 weeks after stroke in patients with proportional or poor recovery. Increases of AD in the motor pathway above stroke foci may be associated with motor recovery after subcortical infarction. Early measurement of diffusion metrics in the ipsilesional non-ischemic motor pathway has limited value in predicting future motor improvement patterns (proportional or poor recovery).

Neural mechanisms and delayed gastric emptying of liquid induced through acute myocardial infarction in rats.

PubMed

Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; Almeida, Eros Antonio de

2015-02-01

In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1 mA/10 s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

Dynamic Magnetic Resonance Angiography Provides Collateral Circulation and Hemodynamic Information in Acute Ischemic Stroke.

PubMed

Hernández-Pérez, María; Puig, Josep; Blasco, Gerard; Pérez de la Ossa, Natalia; Dorado, Laura; Dávalos, Antoni; Munuera, Josep

2016-02-01

Contrary to usual static vascular imaging techniques, contrast-enhanced dynamic magnetic resonance angiography (dMRA) enables dynamic study of cerebral vessels. We evaluated dMRA ability to assess arterial occlusion, cerebral hemodynamics, and collateral circulation in acute ischemic stroke. Twenty-five acute ischemic stroke patients with proximal anterior circulation occlusion underwent dMRA on a 3T scanner within 12 hours of symptoms onset. Diffusion weighted imaging, Tmax6 s lesion volumes and hypoperfusion intensity ratio as volume of Tmax>6 s/volume of Tmax>10 s were measured. Site and grade of occlusion (Thrombolysis in Myocardial Infarction criteria) were evaluated on time-of-flight MRA and dMRA. Leptomeningeal collaterality (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [ASITN/SIR] Scale) and asymmetries in venous clearance were assessed exclusively on dMRA. Collateral filling was dichotomized into incomplete (ASITN/SIR 0-2) or complete (ASITN/SIR 3-4). On dMRA, site of occlusion was M1 in 21 patients, tandem internal carotid artery/M1 in 2 and tandem internal carotid artery/terminal internal carotid artery in 2 patients. Three tandem occlusions were not detected on time-of-flight-MRA. All patients had Thrombolysis in Myocardial Infarction 0 to 1 on time-of-flight-MRA, but three of them had Thrombolysis in Myocardial Infarction 2 on dMRA. Complete collateral filling (n=12, 48%) was associated with smaller diffusion weighted imaging lesion volume (P=0.039), smaller hypoperfused volume (P=0.018), and lower hypoperfusion intensity ratio (P=0.006). Patients with symmetrical clearance of transverse sinuses (52%) were more likely to have complete collateral filling (P=0.015). As a fast, direct, feasible, noninvasive, and reliable method to assess site of occlusion, collateral circulation and hemodynamic alterations, dMRA provides profound insights in acute stroke. © 2015 American Heart Association, Inc.

Regional myocardial velocity imaged by magnetic resonance in patients with ischaemic heart disease.

PubMed Central

Karwatowski, S P; Mohiaddin, R H; Yang, G Z; Firmin, D N; St John Sutton, M; Underwood, S R

1994-01-01

OBJECTIVE--To assess the pattern of global and regional left ventricular long axis motion during early diastole in patients with ischaemic heart disease with and without myocardial infarction using magnetic resonance velocity mapping. DESIGN--Prospective study of 26 patients with a history of myocardial infarction (age 29-78, mean 55 years) and 21 patients with coronary artery disease without infarction (age range 39-71, mean 58 years). Values were compared with a control group (19 controls, age 35-76, mean 52 years) with a low likelihood of cardiovascular disease. RESULTS--Regional long axis velocity varied with time and position around the ventricle. All measurements were taken at the time of maximum early diastolic long axis velocity. Patients with coronary artery disease without infarction had lower values for maximum (mean (SD)) (99 (30) v 125 (33) mm/s, P < 0.05) and mean peak early diastolic wall motion (63 (13) v 82 (22) mm/s, P < 0.05) than controls. The coefficient of variation showed greater inhomogeneity of relaxation in patients than in controls (38 (18)% v 27 (10)%). All values were lower in patients with previous infarction than in patients with coronary artery disease without infarction and normal subjects. In patients with previous myocardial infarction the maximum (mean (SD)) early diastolic velocity was 80 (22) mm/s (P < 0.01 compared with controls and P < 0.05 compared with patients without infarction) and the mean (SD) velocity was 47 (18) mm/s (P < 0.01 compared with controls). The coefficient of variation was greater (52 (33)%) than for controls (P < 0.05) and patients with coronary artery disease without infarction. 18 of 26 patients with previous myocardial infarction and 13 of 21 patients with coronary artery disease without infarction had regional abnormalities corresponding to areas of fixed or reversible ischaemia on exercise electrocardiography or thallium myocardial perfusion tomography. CONCLUSIONS--Magnetic resonance velocity mapping can be used to assess regional long axis myocardial velocity. Ischaemic heart disease causes alterations in the patterns of left ventricular long axis velocity during early diastole. Images PMID:7833190

Evaluating blood-brain barrier permeability in delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

PubMed

Ivanidze, J; Kesavabhotla, K; Kallas, O N; Mir, D; Baradaran, H; Gupta, A; Segal, A Z; Claassen, J; Sanelli, P C

2015-05-01

Patients with SAH are at increased risk of delayed infarction. Early detection and treatment of delayed infarction remain challenging. We assessed blood-brain barrier permeability, measured as permeability surface area product, by using CTP in patients with SAH with delayed infarction. We performed a retrospective study of patients with SAH with delayed infarction on follow-up NCCT. CTP was performed before the development of delayed infarction. CTP data were postprocessed into permeability surface area product, CBF, and MTT maps. Coregistration was performed to align the infarcted region on the follow-up NCCT with the corresponding location on the CTP maps obtained before infarction. Permeability surface area product, CBF, and MTT values were then obtained in the location of the subsequent infarction. The contralateral noninfarcted region was compared with the affected side in each patient. Wilcoxon signed rank tests were performed to determine statistical significance. Clinical data were collected at the time of CTP and at the time of follow-up NCCT. Twenty-one patients with SAH were included in the study. There was a statistically significant increase in permeability surface area product in the regions of subsequent infarction compared with the contralateral control regions (P < .0001). However, CBF and MTT values were not significantly different in these 2 regions. Subsequent follow-up NCCT demonstrated new delayed infarction in all 21 patients, at which time 38% of patients had new focal neurologic deficits. Our study reveals a statistically significant increase in permeability surface area product preceding delayed infarction in patients with SAH. Further investigation of early permeability changes in SAH may provide new insights into the prediction of delayed infarction. © 2015 by American Journal of Neuroradiology.

Delayed brain ischemia tolerance induced by electroacupuncture pretreatment is mediated via MCP-induced protein 1

PubMed Central

2013-01-01

Background Emerging studies have demonstrated that pretreatment with electroacupuncture (EA) induces significant tolerance to focal cerebral ischemia. The present study seeks to determine the involvement of monocyte chemotactic protein-induced protein 1 (MCPIP1), a recently identified novel modulator of inflammatory reactions, in the cerebral neuroprotection conferred by EA pretreatment in the animal model of focal cerebral ischemia and to elucidate the mechanisms of EA pretreatment-induced ischemic brain tolerance. Methods Twenty-four hours after the end of the last EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 minutes in male C57BL/6 mice and MCPIP1 knockout mice. Transcription and expression of MCPIP1 gene was monitored by qRT-PCR, Western blot and immunohistochemistry. The neurobehavioral scores, infarction volumes, proinflammatory cytokines and leukocyte infiltration in brain and NF-κB signaling were evaluated after ischemia/reperfusion. Results MCPIP1 protein and mRNA levels significantly increased specifically in mouse brain undergoing EA pretreatment. EA pretreatment significantly attenuated the infarct volume, neurological deficits, upregulation of proinflammatory cytokines and leukocyte infiltration in the brain of wild-type mice after MCAO compared with that of the non-EA group. MCPIP1-deficient mice failed to evoke EA pretreatment-induced tolerance compared with that of the control MCPIP1 knockout group without EA treatment. Furthermore, the activation of NF-κB signaling was significantly reduced in EA-pretreated wild-type mice after MCAO compared to that of the non-EA control group and MCPIP1-deficient mice failed to confer the EA pretreatment-induced inhibition of NF-κB signaling after MCAO. Conclusions Our data demonstrated that MCPIP1 deficiency caused significant lack of EA pretreatment-induced cerebral protective effects after MCAO compared with the control group and that MCPIP1 is involved in EA pretreatment-induced delayed brain ischemia tolerance. PMID:23663236

Prediction of Reverse Remodeling at Cardiac MR Imaging Soon after First ST-Segment-Elevation Myocardial Infarction: Results of a Large Prospective Registry.

PubMed

Bodi, Vicente; Monmeneu, Jose V; Ortiz-Perez, Jose T; Lopez-Lereu, Maria P; Bonanad, Clara; Husser, Oliver; Minana, Gemma; Gomez, Cristina; Nunez, Julio; Forteza, Maria J; Hervas, Arantxa; de Dios, Elena; Moratal, David; Bosch, Xavier; Chorro, Francisco J

2016-01-01

To assess predictors of reverse remodeling by using cardiac magnetic resonance (MR) imaging soon after ST-segment-elevation myocardial infarction (STEMI). Written informed consent was obtained from all patients, and the study protocol was approved by the institutional committee on human research, ensuring that it conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Five hundred seven patients (mean age, 58 years; age range, 24-89 years) with a first STEMI were prospectively studied. Infarct size and microvascular obstruction (MVO) were quantified at late gadolinium-enhanced imaging. Reverse remodeling was defined as a decrease in left ventricular (LV) end-systolic volume index (LVESVI) of more than 10% from 1 week to 6 months after STEMI. For statistical analysis, a simple (from a clinical perspective) multiple regression model preanalyzing infarct size and MVO were applied via univariate receiver operating characteristic techniques. Patients with reverse remodeling (n = 211, 42%) had a lesser extent (percentage of LV mass) of 1-week infarct size (mean ± standard deviation: 18% ± 13 vs 23% ± 14) and MVO (median, 0% vs 0%; interquartile range, 0%-1% vs 0%-4%) than those without reverse remodeling (n = 296, 58%) (P < .001 in pairwise comparisons). The independent predictors of reverse remodeling were infarct size (odds ratio, 0.98; 95% confidence interval [CI]: 0.97, 0.99; P = .04) and MVO (odds ratio, 0.92; 95% CI: 0.86, 0.99; P = .03). Once infarct size and MVO were dichotomized by using univariate receiver operating characteristic techniques, the only independent predictor of reverse remodeling was the presence of simultaneous nonextensive infarct-size MVO (infarct size < 30% of LV mass and MVO < 2.5% of LV mass) (odds ratio, 3.2; 95% CI: 1.8, 5.7; P < .001). Assessment of infarct size and MVO with cardiac MR imaging soon after STEMI enables one to make a decision in the prediction of reverse remodeling. © RSNA, 2015

Non-Selective Calcium Channel Blocker Bepridil Decreases Secondary Pathology in Mice after Photothrombotic Cortical Lesion

PubMed Central

Lipsanen, Anu; Flunkert, Stefanie; Kuptsova, Kristina; Hiltunen, Mikko; Windisch, Manfred; Hutter-Paier, Birgit; Jolkkonen, Jukka

2013-01-01

Experimental studies have identified a complex link between neurodegeneration, β-amyloid (Aβ) and calcium homeostasis. Here we asked whether early phase β-amyloid pathology in transgenic hAPPSL mice exaggerates the ischemic lesion and remote secondary pathology in the thalamus, and whether a non-selective calcium channel blocker reduces these pathologies. Transgenic hAPPSL (n = 33) and non-transgenic (n = 30) male mice (4–5 months) were subjected to unilateral cortical photothrombosis and treated with the non-selective calcium channel blocker bepridil (50 mg/kg, p.o., once a day) or vehicle for 28 days, starting administration 2 days after the operation. Animals were then perfused for histological analysis of infarct size, Aβ and calcium accumulation in the thalamus. Cortical photothrombosis resulted in a small infarct, which was associated with atypical Aβ and calcium accumulation in the ipsilateral thalamus. Transgenic mice had significantly smaller infarct volumes than non-transgenic littermates (P<0.05) and ischemia-induced rodent Aβ accumulation in the thalamus was lower in transgenic mice compared to non-transgenic mice (P<0.01). Bepridil decreased calcium load in the thalamus (P<0.01). The present data suggest less pronounced primary and secondary pathology in hAPPSL transgenic mice after ischemic cortical injury. Bepridil particularly decreased calcium pathology in the thalamus following ischemia. PMID:23555933

[Clinical implications and angiographic and electrocardiographic correlation of ST segment elevation in leads V7-V9 in patients with ST elevation myocardial infarction].

PubMed

Adawi, Khaled; Atar, Shaul

2008-07-01

The clinical significance and clinical characteristics of patients with myocardial infarction involving the posterior wall of the left ventricle is not well-defined. The angiographic findings and their correlation with the eletrocardiographic (ECG) findings may be of high therapeutic importance. We retrospectively studied consecutive patients with ST elevation myocardial infarction on the admission ECG to the intensive cardiac care. We studied the clinical and demographic characteristics, the clinical course in-hospital and the clinical outcome (including infarct size, congestive heart failure and significant mitral insufficiency). All patients underwent coronary angiography during the index admission. We correlated the ECG findings on admission to the angiographic findings. We studied 198 patients with mean age of 57 +/- 12 years (range 30-88 years), 158 men (79.8%) and 40 women (20.2%). Myocardial infarction involving the inferior wall was noted in 119 patients, of whom 68 had inferior wall myocardial infarction only, and 51 had inferior and lateral wall involvement (leads I, AVL and/or V5-V6). Only 4 patients (2%) had ST elevation in leads V7-V9 only. The left ventricular ejection fraction was lowest in patients with anterior wall myocardial infarction (41% +/- 6) compared to myocardial infarction with the posterior wall involved (44% +/- 8) or myocardial infarction with the inferior wall only (54% +/- 6) (p = 0.023). The largest infarct size by peak creatine phosphokinase was found in the inferoposterior myocardial infarction group, significantly larger from inferior infarction only, and similar to that of anterior myocardial infarction. The incidence of congestive heart failure was slightly more in anterior myocardial infarction; however, significant mitral valve insufficiency was higher in patients with posterior wall involvement, yet with no statistical significance. The infarct related artery causing posterior myocardial infarction was significantly more frequent in the right coronary artery (57.1%) compared to the left circumflex artery (37.5%) (p < 0.01). The major artery causing involvement of the posterior wall is the right coronary artery. In patients with myocardial infarction involving the posterior wall, infarct size is similar to that of anterior wall myocardial infarction, and with similar complications rate. However, the incidence of significant mitral valve insufficiency and congestive heart failure is high in patients with posterior wall involvement. Posterior leads assessment should be conducted routinely in patients with suspected myocardial infarction.

The Sigma-1 Receptor Antagonist, S1RA, Reduces Stroke Damage, Ameliorates Post-Stroke Neurological Deficits and Suppresses the Overexpression of MMP-9.

PubMed

Sánchez-Blázquez, Pilar; Pozo-Rodrigálvarez, Andrea; Merlos, Manuel; Garzón, Javier

2018-06-01

The glutamate N-methyl-D-aspartate receptor (NMDAR) plays an essential role in the excitotoxic neural damage that follows ischaemic stroke. Because the sigma-1 receptor (σ1R) can regulate NMDAR transmission, exogenous and putative endogenous regulators of σ1R have been investigated using animal models of ischaemic stroke. As both agonists and antagonists provide some neural protection, the selective involvement of σ1Rs in these effects has been questioned. The availability of S1RA (E-52862/MR309), a highly selective σ1R antagonist, prompted us to explore its therapeutic potential in an animal model of focal cerebral ischaemia. Mice were subjected to right middle cerebral artery occlusion (MCAO), and post-ischaemic infarct volume and neurological deficits were determined across a range of intervals after the stroke-inducing surgery. Intracerebroventricular or intravenous treatment with S1RA significantly reduced the cerebral infarct size and neurological deficits caused by permanent MCAO (pMCAO). Compared with the control/sham-operated mice, the neuroprotective effects of S1RA were observed when delivered up to 5 h prior to surgery and 3 h after ischaemic onset. Interestingly, neither mice with the genetic deletion of σ1R nor wild-type mice that were pre-treated with the σ1R agonist PRE084 showed beneficial effects after S1RA administration with regard to stroke infarction. S1RA-treated mice showed faster behavioural recovery from stroke; this finding complements the significant decreases in matrix metalloproteinase-9 (MMP-9) expression and reactive astrogliosis surrounding the infarcted cortex. Our data indicate that S1RA, via σ1R, holds promising potential for clinical application as a therapeutic agent for ischaemic stroke.

Heart Rate Reduction With Ivabradine Protects Against Left Ventricular Remodeling by Attenuating Infarct Expansion and Preserving Remote-Zone Contractile Function and Synchrony in a Mouse Model of Reperfused Myocardial Infarction.

PubMed

O'Connor, Daniel M; Smith, Robert S; Piras, Bryan A; Beyers, Ronald J; Lin, Dan; Hossack, John A; French, Brent A

2016-04-22

Ivabradine selectively inhibits the pacemaker current of the sinoatrial node, slowing heart rate. Few studies have examined the effects of ivabradine on the mechanical properties of the heart after reperfused myocardial infarction (MI). Advances in ultrasound speckle-tracking allow strain analyses to be performed in small-animal models, enabling the assessment of regional mechanical function. After 1 hour of coronary occlusion followed by reperfusion, mice received 10 mg/kg per day of ivabradine dissolved in drinking water (n=10), or were treated as infarcted controls (n=9). Three-dimensional high-frequency echocardiography was performed at baseline and at days 2, 7, 14, and 28 post-MI. Speckle-tracking software was used to calculate intramural longitudinal myocardial strain (Ell) and strain rate. Standard deviation time to peak radial strain (SD Tpeak Err) and temporal uniformity of strain were calculated from short-axis cines acquired in the left ventricular remote zone. Ivabradine reduced heart rate by 8% to 16% over the course of 28 days compared to controls (P<0.001). On day 28 post-MI, the ivabradine group was found to have significantly smaller end-systolic volumes, greater ejection fraction, reduced wall thinning, and greater peak Ell and Ell rate in the remote zone, as well as globally. Temporal uniformity of strain and SD Tpeak Err were significantly smaller in the ivabradine-treated group by day 28 (P<0.05). High-frequency ultrasound speckle-tracking demonstrated decreased left ventricular remodeling and dyssynchrony, as well as improved mechanical performance in remote myocardium after heart rate reduction with ivabradine. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Prediction of myocardial functional recovery by noninvasive evaluation of Basal and hyperemic coronary flow in patients with previous myocardial infarction.

PubMed

Djordjevic-Dikic, Ana; Beleslin, Branko; Stepanovic, Jelena; Giga, Vojislav; Tesic, Milorad; Dobric, Milan; Stojkovic, Sinisa; Nedeljkovic, Milan; Vukcevic, Vladan; Dikic, Nenad; Petrasinovic, Zorica; Nedeljkovic, Ivana; Tomasevic, Miloje; Vujisic-Tesic, Bosiljka; Ostojic, Miodrag

2011-05-01

The aim of this study was to evaluate the relation of basal and hyperemic coronary flow with myocardial functional improvement in patients with previous myocardial infarction undergoing elective percutaneous coronary intervention (PCI). Coronary flow was measured using transthoracic Doppler echocardiography in 50 patients (41 men; mean age, 53 ± 8 years) with previous myocardial infarction before, 24 hours, and 3 months after elective PCI. Diastolic deceleration time (DDT) was measured from the peak diastolic velocity to the point of intercept of initial decay slope with baseline. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic to basal peak diastolic flow velocities. In comparison with patients without improvements in left ventricular function, patients with recovered left ventricular function had longer DDTs before angioplasty (841 ± 286 vs. 435 ± 80 msec, P < .001). CFR was significantly higher in recovered compared with nonrecovered patients (2.60 ± 0.70 vs. 2.16 ± 0.34, P = .034) 24 hours after PCI. Global and regional wall motion scores before PCI, end-diastolic and end-systolic volumes, and CFR 24 hours after PCI and DDT before PCI were univariate predictors of left ventricular functional recovery. By multivariate analysis, DDT and regional wall motion score before PCI were independent predictors of left ventricular recovery in the follow-up period (P = .003 and P = .007, respectively). In patients with previous myocardial infarction undergoing elective PCI, evaluation of basal coronary flow pattern and measurement of DDT before angioplasty may predict functional improvement of myocardium in the follow-up period and could be useful quantitative parameters in the evaluation of potential improvement in myocardial function. Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Heart-Derived Stem Cells in Miniature Swine with Coronary Microembolization: Novel Ischemic Cardiomyopathy Model to Assess the Efficacy of Cell-Based Therapy

PubMed Central

Young, Rebeccah F.; Leiker, Merced M.; Suzuki, Takayuki

2016-01-01

A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 106 microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n = 11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 106, n = 5) or saline (untreated, n = 6). Four weeks after therapy myocardial function, myocyte proliferation (Ki67), mitosis (phosphor-Histone H3; pHH3), apoptosis, infarct size (TTC), myocyte nuclear density, and cell size were evaluated. CDCs injected into infarcted and remodeled remote myocardium (global infusion) increased regional function and global function contrasting no change in untreated animals. CDCs reduced infarct volume and stimulated Ki67 and pHH3 positive myocytes in infarct and remote regions. As a result, myocyte number (nuclear density) increased and myocyte cell diameter decreased in both infarct and remote regions. Coronary microembolization produces stable long-term ischemic cardiomyopathy. Global infusion of CDCs stimulates myocyte regeneration and improves left ventricular ejection fraction. Thus, global infusion of CDCs could become a new therapy to reverse LV dysfunction in patients with asymptomatic heart failure. PMID:27738436

Macrophage Migration Inhibitory Factor for the Early Prediction of Infarct Size

PubMed Central

Chan, William; White, David A.; Wang, Xin‐Yu; Bai, Ru‐Feng; Liu, Yang; Yu, Hai‐Yi; Zhang, You‐Yi; Fan, Fenling; Schneider, Hans G.; Duffy, Stephen J.; Taylor, Andrew J.; Du, Xiao‐Jun; Gao, Wei; Gao, Xiao‐Ming; Dart, Anthony M.

2013-01-01

Background Early diagnosis and knowledge of infarct size is critical for the management of acute myocardial infarction (MI). We evaluated whether early elevated plasma level of macrophage migration inhibitory factor (MIF) is useful for these purposes in patients with ST‐elevation MI (STEMI). Methods and Results We first studied MIF level in plasma and the myocardium in mice and determined infarct size. MI for 15 or 60 minutes resulted in 2.5‐fold increase over control values in plasma MIF levels while MIF content in the ischemic myocardium reduced by 50% and plasma MIF levels correlated with myocardium‐at‐risk and infarct size at both time‐points (P<0.01). In patients with STEMI, we obtained admission plasma samples and measured MIF, conventional troponins (TnI, TnT), high sensitive TnI (hsTnI), creatine kinase (CK), CK‐MB, and myoglobin. Infarct size was assessed by cardiac magnetic resonance (CMR) imaging. Patients with chronic stable angina and healthy volunteers were studied as controls. Of 374 STEMI patients, 68% had elevated admission MIF levels above the highest value in healthy controls (>41.6 ng/mL), a proportion similar to hsTnI (75%) and TnI (50%), but greater than other biomarkers studied (20% to 31%, all P<0.05 versus MIF). Only admission MIF levels correlated with CMR‐derived infarct size, ventricular volumes and ejection fraction (n=42, r=0.46 to 0.77, all P<0.01) at 3 day and 3 months post‐MI. Conclusion Plasma MIF levels are elevated in a high proportion of STEMI patients at the first obtainable sample and these levels are predictive of final infarct size and the extent of cardiac remodeling. PMID:24096574

Estimation of infarct size using transthoracic Doppler echocardiographic measurement of coronary flow reserve in infarct related and reference coronary artery.

PubMed

Giga, Vojislav; Dobric, Milan; Beleslin, Branko; Sobic-Saranovic, Dragana; Tesic, Milorad; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Nedeljkovic, Ivana; Artiko, Vera; Obradovic, Vladimir; Seferovic, Petar M; Ostojic, Miodrag

2013-09-20

Patients in chronic phase of myocardial infarction (MI) have decreased coronary flow reserve (CFR) in infarct related artery (IRA) that is proportional to the extent of microvascular/myocardial damage. We proposed a novel model for the assessment of microvascular damage and infarct size using Doppler echocardiography evaluation of CFRs of the IRA (LAD) and reference artery (RCA). Our study included 34 consecutive patients (28 men, mean age 50 ± 11 years) with first anterior STEMI and single vessel disease successfully treated with primary PCI. All patients underwent SPECT MPI for the assessment of infarct size (expressed as a percentage of myocardium with fixed perfusion abnormalities) and CFR evaluation of LAD and RCA. CFR derived percentage of microvascular damage (CFR PMD) was calculated as: CFR PMD=(CFR RCA-CFR LAD)/(CFR RCA-1)×100 (%). CFR PMD correlated significantly with all parameters evaluating the severity of myocardial damage including: peak CK activity (r=0.632, p<0.001), WMSI (r=0.857, p<0.001), ejection fraction (r=-0.820, p<0.001), left ventricular end diastolic (r=0.757, p<0.001) and end systolic volume (r=0.794, p<0.001). Most importantly, CFR PMD (22 ± 17%) correlated significantly with infarct size by SPECT MPI (21 ± 17%) (r=0.874, p<0.001). CFR PMD derived from the proposed model was significantly related to echocardiographic and enzymatic parameters of infarct size, as well as to myocardial damage assessed by SPECT MPI in patients with successfully reperfused first anterior STEMI. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Epicardial catheter-based ventricular reconstruction: a novel therapy for ischaemic heart failure with anteroapical aneurysm†

PubMed Central

Cheng, Yanping; Aboodi, Michael S.; Wechsler, Andrew S.; Kaluza, Greg L.; Granada, Juan F.; Van Bladel, Kevin; Annest, Lon S.; Yi, Geng-Hua

2013-01-01

OBJECTIVES Surgical ventricular reconstruction has been used to treat ischaemic cardiomyopathy with large akinetic or dyskinetic areas. However, application of this approach requires a sternotomy, cardiopulmonary bypass and a left ventriculotomy. This study assessed the feasibility and efficacy of minimally invasive, off-pump, epicardial catheter-based ventricular reconstruction (ECVR) in an anteroapical aneurysm ovine model. METHODS Left ventricular (LV) anteroapical myocardial infarction was induced percutaneously by coil embolization of the left anterior descending coronary artery. Eight weeks after infarction, via mini left thoracotomy and without cardiopulmonary bypass, ECVR was performed in six sheep. The scar was excluded by placing anchor pairs on the LV epicardial anterior wall and the right ventricular side of the interventricular septum under fluoroscopic guidance. LV performance was evaluated before, immediately after device implantation and after 6 weeks by echocardiography. Terminal histopathology was performed. RESULTS ECVR was completed expeditiously in all animals without complications. Parameters obtained 6 weeks after device implantation were compared with baseline (pre-device). End-systolic volume was decreased by 38% (25.6 ± 6.1 ml vs baseline 41.2 ± 7.2 ml, P = 0.02) with preservation of stroke volume. Ejection fraction was significantly increased by 13% (48.5 ± 7% vs baseline 35.8 ± 7%, P = 0.02). The circumferential strain in the anterior septum (−7.67 ± 5.12% vs baseline −0.96 ± 2.22%, P = 0.03) and anterior wall (−9.01 ± 3.51% vs baseline −4.15 ± 1.36%, P = 0.01) were significantly improved. The longitudinal strain in apex was reversed (−3.08 ± 1.53% vs baseline 3.09 ± 3.39%, P = 0.01). Histopathology showed full endocardial healing over the anchors with appreciable reduction of the chronic infarct in the LV. CONCLUSIONS ECVR without cardiopulmonary bypass is a less invasive alternative to current standard therapies, reverses LV remodelling and improves cardiac performance in an ovine model of anteroapical aneurysm. PMID:23985410

Hexane extracts of Polygonum multiflorum improve tissue and functional outcome following focal cerebral ischemia in mice.

PubMed

Lee, Soo Vin; Choi, Kyung Ha; Choi, Young Whan; Hong, Jin Woo; Baek, Jin Ung; Choi, Byung Tae; Shin, Hwa Kyoung

2014-04-01

Polygonum multiflorum is a traditional Korean medicine that has been utilized widely in East Asian countries as a longevity agent. Clinical studies have demonstrated that Polygonum multiflorum improves hypercholesterolemia, coronary heart disease, neurosis and other diseases commonly associated with aging. However, scientific evidence defining the protective effects and mechanisms of Polygonum multiflorum against ischemic stroke is incomplete. In the present study, we investigated the cerebrovascular protective effects of Polygonum multiflorum against ischemic brain injury using an in vivo photothrombotic mouse model. To examine the underlying mechanism of action, we utilized an in vitro human brain microvascular endothelial cell (HBMEC) culture system. Hexane extracts (HEPM), ethyl acetate extracts (EAEPM) and methanol extracts (MEPM) of Polygonum multiflorum (100 mg/kg) were administered intraperitoneally 30 min prior to ischemic insult. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, as well as neurological and motor function, 24 h after ischemic brain injury. Following ischemic insult, HEPM induced a significant reduction in infarct volume and subsequent neurological deficits, compared with EAEPM and MEPM. HEPM significantly decreased infarct size and improved neurological and motor function, which was not observed in eNOS KO mice, suggesting that this cerebroprotective effect is primarily an eNOS-dependent mechanism. In vitro, HEPM effectively promoted NO production, however these effects were inhibited by the NOS inhibitor, L-NAME and the PI3K/Akt inhibitor, LY-294002. Furthermore, HEPM treatment resulted in increased phosphorylation-dependent activation of Akt and eNOS in HBMEC, suggesting that HEPM increased NO production via phosphorylation-dependent activation of Akt and eNOS. In conclusion, HEPM prevents cerebral ischemic damage through an eNOS-dependent mechanism, and thus may have clinical applications as a protective agent against neurological injury in stroke.

Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction

PubMed Central

Russell, Richard O.; Rackley, Charles E.; Pombo, Jaoquin; Hunt, David; Potanin, Constantine; Dodge, Harold T.

1970-01-01

Left ventricular performance in 19 patients with acute myocardial infarction has been evaluated by measuring left ventricular response in terms of cardiac output, stroke volume, work, and power to progressive elevation of filling pressure accomplished by progressive expansion of blood volume with rapid infusion of low molecular weight dextran. Such infusion can elevate the cardiac output, stroke volume, work, and power and thus delineate the function of the left ventricle by Frank-Starling function curves. Left ventricular filling pressure in the range of 20-24 mm Hg was associated with the peak of the curves and when the filling pressure exceeded this range, the curves became flattened or decreased. An increase in cardiac output could be maintained for 4 or more hr. Patients with a flattened function curve had a high mortality in the ensuing 8 wk. The function curve showed improvement in myocardial function during the early convalescence. When left ventricular filling pressure is monitored directly or as pulmonary artery end-diastolic pressure, low molecular weight dextran provides a method for assessment of left ventricular function. Images PMID:5431663

An approach to the diagnosis of metabolic syndrome by the multi-electrode impedance method

NASA Astrophysics Data System (ADS)

Furuya, N.; Sakamoto, K.; Kanai, H.

2010-04-01

It is well known that metabolic syndrome can induce myocardial infarction and cerebral infarction. So, it is very important to measure the visceral fat volume. In the electric impedance method, information in the vicinity of the electrodes is strongly reflected. Therefore, we propose a new multi-electrode arrangement method based on the impedance sensitivity theorem to measure the visceral fat volume. This electrode arrangement is designed to enable high impedance sensitivity in the visceral and subcutaneous fat regions. Currents are simultaneously applied to several current electrodes on the body surface, and one voltage electrode pair is arranged on the body surface near the organ of interest to obtain the visceral fat information and another voltage electrode pair is arranged on the body surface near the current electrodes to obtain the subcutaneous fat information. A simulation study indicates that by weighting the impedance sensitivity distribution, as in our method, a high-sensitivity region in the visceral and the subcutaneous fat regions can be formed. In addition, it was confirmed that the visceral fat volume can be estimated by the measured impedance data.

Metabolic Syndrome is Associated With Higher Wall Motion Score and Larger Infarct Size After Acute Myocardial Infarction

PubMed Central

Hajsadeghi, Shokoufeh; Chitsazan, Mitra; Chitsazan, Mandana; Haghjoo, Majid; Babaali, Nima; Norouzzadeh, Zahra; Mohsenian, Maryam

2015-01-01

Background: Infarct size is an important surrogate end point for early and late mortality after acute myocardial infarction. Despite the high prevalence of metabolic syndrome in patients with atherosclerotic diseases, adequate data are still lacking regarding the extent of myocardial necrosis after acute myocardial infarction in these patients. Objectives: In the present study we aimed to compare myocardial infarction size in patients with metabolic syndrome to those without metabolic syndrome using peak CK-MB and cardiac troponin I (cTnI) at 72 hours after the onset of symptoms. Patients and Methods: One-hundred patients with metabolic syndrome (group I) and 100 control subjects without metabolic syndrome (group II) who experienced acute myocardial infarction were included in the study. Diagnosis of metabolic syndrome was based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines published in 2001. Myocardial infarction size was compared between the two groups of patients using peak CK-MB and cTnI level in 72 hours after the onset of symptoms. Results: Peak CK-MB and cTnI in 72 hours were found to be significantly higher in patients with metabolic syndrome compared with control subjects (both P < 0.001). Patients with metabolic syndrome also had markedly higher wall motion abnormality at 72 hours after the onset of symptoms as assessed by echocardiographically-derived Wall Motion Score Index (WMSI) (P < 0.001). Moreover, statistically significant relationships were found between WMSI and peak CK-MB and also cTnI at 72 hours (Spearman's rho = 0.56, P < 0.001 and Spearman's rho = 0.5, P < 0.001; respectively). However, association between WMSI and left ventricular ejection fraction was insignificant (Spearman's rho = -0.05, P = 0.46). Conclusions: We showed that patients with metabolic syndrome have larger infarct size compared to control subjects. PMID:25789257

Venlafaxine treatment after endothelin-1-induced cortical stroke modulates growth factor expression and reduces tissue damage in rats.

PubMed

Zepeda, Rodrigo; Contreras, Valentina; Pissani, Claudia; Stack, Katherine; Vargas, Macarena; Owen, Gareth I; Lazo, Oscar M; Bronfman, Francisca C

2016-08-01

Neuromodulators, such as antidepressants, may contribute to neuroprotection by modulating growth factor expression to exert anti-inflammatory effects and to support neuronal plasticity after stroke. Our objective was to study whether early treatment with venlafaxine, a serotonin-norepinephrine reuptake inhibitor, modulates growth factor expression and positively contributes to reducing the volume of infarcted brain tissue resulting in increased functional recovery. We studied the expression of BDNF, FGF2 and TGF-β1 by examining their mRNA and protein levels and cellular distribution using quantitative confocal microscopy at 5 days after venlafaxine treatment in control and infarcted brains. Venlafaxine treatment did not change the expression of these growth factors in sham rats. In infarcted rats, BDNF mRNA and protein levels were reduced, while the mRNA and protein levels of FGF2 and TGF-β1 were increased. Venlafaxine treatment potentiated all of the changes that were induced by cortical stroke alone. In particular, increased levels of FGF2 and TGF-β1 were observed in astrocytes at 5 days after stroke induction, and these increases were correlated with decreased astrogliosis (measured by GFAP) and increased synaptophysin immunostaining at twenty-one days after stroke in venlafaxine-treated rats. Finally, we show that venlafaxine reduced infarct volume after stroke resulting in increased functional recovery, which was measured using ladder rung motor tests, at 21 days after stroke. Our results indicate that the early oral administration of venlafaxine positively contributes to neuroprotection during the acute and late events that follow stroke. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hemin offers neuroprotection through inducing exogenous neuroglobin in focal cerebral hypoxic-ischemia in rats

PubMed Central

Song, Xue; Xu, Rui; Xie, Fei; Zhu, Haiyuan; Zhu, Ji; Wang, Xin

2014-01-01

Objective: To investigate the inducible effect of hemin on exogenous neuroglobin (Ngb) in focal cerebral hypoxic-ischemia in rats. Methods: 125 healthy SD rats were randomly divided into five groups: sham-operation control group, operation group, hemin treatment group, exogenous Ngb treatment group, and hemin and exogenous Ngb joint treatment group. Twenty-four hours after focal cerebral hypoxic-ischemia, Ngb expression was evaluated by immunocytochemistry, RT-PCR, and western blot analyses, while the brain water content and infarct volume were examined. Results: Immunocytochemistry, RT-PCR, and western blot analyses showed more pronounced Ngb expression in the hemin and exogenous Ngb joint operation group than in the hemin or exogenous Ngb individual treatment groups, thus producing significant differences in brain water content and infarct volume (p < 0.05). Conclusions: Hemin may be beneficial in protecting against focal cerebral hypoxic-ischemia through inducing the expression of exogenous Ngb. PMID:24966924

Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data.

PubMed

Gyöngyösi, Mariann; Wojakowski, Wojciech; Lemarchand, Patricia; Lunde, Ketil; Tendera, Michal; Bartunek, Jozef; Marban, Eduardo; Assmus, Birgit; Henry, Timothy D; Traverse, Jay H; Moyé, Lemuel A; Sürder, Daniel; Corti, Roberto; Huikuri, Heikki; Miettinen, Johanna; Wöhrle, Jochen; Obradovic, Slobodan; Roncalli, Jérome; Malliaras, Konstantinos; Pokushalov, Evgeny; Romanov, Alexander; Kastrup, Jens; Bergmann, Martin W; Atsma, Douwe E; Diederichsen, Axel; Edes, Istvan; Benedek, Imre; Benedek, Theodora; Pejkov, Hristo; Nyolczas, Noemi; Pavo, Noemi; Bergler-Klein, Jutta; Pavo, Imre J; Sylven, Christer; Berti, Sergio; Navarese, Eliano P; Maurer, Gerald

2015-04-10

The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy. We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters. This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591. © 2015 American Heart Association, Inc.

Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine.

PubMed

Chen, Jiann-Hwa; Kuo, Hsing-Chun; Lee, Kam-Fai; Tsai, Tung-Hu

2014-09-15

Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groups with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3β and NF-κB. Copyright © 2014 Elsevier Inc. All rights reserved.

The sensorimotor and cognitive deficits in rats following 90- and 120-min transient occlusion of the middle cerebral artery.

PubMed

Zvejniece, Liga; Svalbe, Baiba; Liepinsh, Edgars; Pulks, Eduards; Dambrova, Maija

2012-07-15

Middle cerebral artery occlusion (MCAO) is the most commonly used method to study the neurological and histological outcomes and the pathological mechanisms of ischaemic stroke. The current work compares sensorimotor and cognitive deficits and the infarct volume in rats following a transient 90- or 120-min MCAO, which allows the appropriate behavioural tests to be chosen based on the goal and design of the experiment. In the beam-walking test, we found significant differences between the 90- and 120-min MCAO groups in the number of foot faults made with the impaired hindlimb on post-stroke days 3, 7 and 14. In the cylinder test, a difference between the 90- and 120-min groups was observed on post-operation day 14. The responses to tactile and proprioceptive stimulation were impaired to a similar extent after 90- and 120-min MCAO in the vibrissae-evoked forelimb-placing and limb-placing tests. Moreover, we found significant memory impairment in the 120-min MCAO group 6 days after the acquisition trial. The brain tissue damage was significantly higher after 120-min occlusion of the MCA compared with 90-min occlusion; the infarct volumes were 13% and 25% of the contralateral hemispheres, respectively. In conclusion, both the 90- and 120-min occlusion models result in a significant impairment of sensorimotor, tactile and proprioceptive function, but memory impairment is only observed in the 120-min MCAO group. The beam-walking and cylinder tests detected neurological dysfunction after the 120-min MCAO, whereas the limb-placing and vibrissae-evoked forelimb-placing tests were able to evaluate the neurological dysfunction in rats after 90- and 120-min MCAO. Copyright © 2012 Elsevier B.V. All rights reserved.

Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.

PubMed

Cheng, Zhuo; Wang, Liping; Qu, Meijie; Liang, Huaibin; Li, Wanlu; Li, Yongfang; Deng, Lidong; Zhang, Zhijun; Yang, Guo-Yuan

2018-05-03

Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 10 5 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p < 0.05). IgG leakage, tight junction protein loss, and inflammatory cytokines IL-1β, IL-6, and TNF-α reduced in mesenchymal stem cell-treated mice compared to the control group following ischemia (p < 0.05). After transplantation, MMP-9 was decreased in protein and activity levels as compared with controls (p < 0.05). Furthermore, myeloperoxidase-positive cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p < 0.05). The results showed that mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.

Predicting Hemorrhagic Transformation of Acute Ischemic Stroke: Prospective Validation of the HeRS Score.

PubMed

Marsh, Elisabeth B; Llinas, Rafael H; Schneider, Andrea L C; Hillis, Argye E; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F

2016-01-01

Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort.A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis.Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P < 0.001), white blood cell count (P < 0.001), and warfarin use prior to admission (P = 0.002) were also associated with HT in the validation cohort. With these variables, AUC improved to 0.854. Anticoagulation did not significantly increase HT; but with higher intensity anticoagulation, hemorrhages were more likely to be symptomatic and more severe.The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation.

Neuroprotective effects of chloroform and petroleum ether extracts of Nigella sativa seeds in stroke model of rat

PubMed Central

Akhtar, Mohammad; Maikiyo, Aliyu Muhammad; Najmi, Abul Kalam; Khanam, Razia; Mujeeb, Mohd; Aqil, Mohd

2013-01-01

PURPOSE: Stroke still remains a challenge for the researchers and scientists for developing ideal drug. Several new drugs are being evaluated showing excellent results in preclinical studies but when tested in clinical trials, they failed. Many herbal drugs in different indigenous system of medicine claim to have beneficial effects but not extensively evaluated for stroke (cerebral ischemia). AIM: The present study was undertaken to evaluate chloroform and petroleum ether extract of Nigella sativa seeds administered at a dose of 400 mg/kg, per orally for seven days in middle cerebral artery occluded (MCAO) rats for its neuroprotective role in cerebral ischemia. MATERIALS AND METHODS: Focal cerebral ischemia was induced by middle cerebral artery occlusion for two hours followed by reperfusion for 22 hours. After 24 hours, grip strength, locomotor activity tests were performed in different treatment groups of rats. After completing behavioral tests, animals were sacrificed; brains were removed for the measurement of infarct volume followed by the estimation of markers of oxidative stress. RESULTS: Both chloroform and petroleum ether extracts-pretreated rats showed improvement in locomotor activity and grip strength, reduced infarct volume when compared with MCAO rats. MCA occlusion resulted in the elevation of levels of thiobarbituric acid reactive substance (TBARS), while a reduction in the levels of glutathione (GSH) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase levels were observed. Pre-treatment of both extracts of Nigella sativa showed reduction in TBARS, elevation in glutathione, SOD, and catalase levels when compared with MCAO rats. CONCLUSION: The chloroform and petroleum ether extract of Nigella sativa showed the protective effects in cerebral ischemia. The present study confirms the antioxidant, free radical scavenging, and anti-inflammatory properties of Nigella sativa already reported. PMID:23833517

Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools.

PubMed

Kelsen, Jesper; Larsen, Marianne H; Sørensen, Jens Christian; Møller, Arne; Frøkiaer, Jørgen; Nielsen, Søren; Nyengaard, Jens R; Mikkelsen, Jens D; Rønn, Lars Christian B

2010-04-06

We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats (SHRs) and Sprague-Dawley rats (SDs) one week after tMCAo; (2) to present the practical use of the optical fractionator and 2D nucleator in stereological brain tissue analyses; and (3) to report our experiences with an intraluminal tMCAo model where the occluding filament is advanced 22 mm beyond the carotid bifurcation and the common carotid artery is clamped during tMCAo. Twenty-three SDs and twenty SHRs were randomized into four groups subjected to 90 minutes tMCAo or sham. BrdU (50 mg/kg) was administered intraperitoneally twice daily on Day 4 to 7 after surgery. On Day 8 all animals were euthanized. NeuN-stained tissue sections were used for brain and infarct volume estimation with the 2D nucleator and Cavalieri principle. Brains were studied for the presence of activated microglia (ED-1) and hippocampal BrdU incorporation using the optical fractionator. We found no significant difference or increase in post-ischemic NPC proliferation between the two strains. However, the response to remote ischemia may differ between SDs and SHRs. In three animals increased post-stroke NPC proliferation was associated with hippocampal ischemic injury. The mean infarct volume was 89.2 +/- 76.1 mm3 in SHRs and 16.9 +/- 22.7 mm3 in SDs (p < 0.005). Eight out of eleven SHRs had ischemic neocortical damage in contrast to only one out of 12 SDs. We observed involvement of the anterior choroidal and hypothalamic arteries in several animals from both strains and the anterior cerebral artery in two SHRs. We found no evidence of an early hippocampal NPC proliferation one week after tMCAo in both strains. Infarction within the anterior choroidal artery could induce hippocampal ischemia and increase NPC proliferation profoundly. NPC proliferation was not aggravated by the presence of activated microglia. Intraluminal tMCAo in SHRs gave a more reliable infarct with neocortical involvement, but affected territories supplied by the anterior cerebral, anterior choroidal and hypothalamic arteries.

Adult Bone Marrow Cell Therapy for Ischemic Heart Disease: Evidence and Insights from Randomized Controlled Trials

PubMed Central

Afzal, Muhammad R.; Samanta, Anweshan; Shah, Zubair I.; Jeevanantham, Vinodh; Abdel-Latif, Ahmed; Zuba-Surma, Ewa K.; Dawn, Buddhadeb

2015-01-01

Rationale Notwithstanding the uncertainties regarding the outcomes of BMC therapy for heart repair, further insights are critically needed to improve this promising approach. Objective To delineate the true impact of BMC therapy for cardiac repair and gain insights for future trials through systematic review and meta-analysis of data from eligible randomized controlled trials (RCTs). Methods and Results Database searches through August 2014 identified forty-eight eligible RCTs (enrolling 2602 patients). Weighted mean differences for changes in left ventricular (LV) ejection fraction (EF), infarct size, LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV) were analyzed with random-effects meta-analysis. Compared with standard therapy, BMC transplantation improved LVEF (2.92%; 95% confidence interval [CI], 1.91 to 3.92; P<0.00001), reduced infarct size (−2.25%; 95% CI, −3.55 to −0.95; P=0.0007) and LVESV (−6.37 ml; 95% CI, −8.95 to −3.80; P<0.00001), and tended to reduce LVEDV (−2.26 ml; 95% CI, −4.59 to 0.07; P=0.06). Similar effects were noted when data were analyzed after excluding studies with discrepancies in outcomes reporting. The benefits also persisted when cardiac catheterization was performed in control patients as well. Although imaging modalities partly influenced the outcomes, LVEF improved in BMC-treated patients when assessed by MRI. Early (<48h) BMC injection after MI was more effective in reducing infarct size, while BMC injection between 3 and 10 days proved superior toward improving systolic function. A minimum of 50 million BMCs seemed to be necessary, with limited additional benefits seen with increasing cell numbers. BMC therapy was safe and improved clinical outcomes, including all-cause mortality, recurrent MI, ventricular arrhythmia, and cerebrovascular accident (CVA) during follow-up, albeit with differences between acute MI and chronic IHD subgroups. Conclusions Transplantation of adult BMCs improves LVEF, reduces infarct size and ameliorates remodeling in patients with IHD. These effects are upheld in analyses of studies employing MRI, and also after excluding studies with discrepant outcomes reporting. BMC transplantation may also reduce the incidence of death, recurrent MI, ventricular arrhythmia, and CVA during follow-up. PMID:26160853

Cardiologist service volume, percutaneous coronary intervention and hospital level in relation to medical costs and mortality in patients with acute myocardial infarction: a nationwide study.

PubMed

Liu, C-Y; Lin, Y-N; Lin, C-L; Chang, Y-J; Hsu, Y-H; Tsai, W-C; Kao, C-H

2014-07-01

We explore whether cardiologist service volume, hospital level and percutaneous coronary intervention (PCI) are associated with medical costs and acute myocardial infarction (AMI) mortality. From the 1997-2010 Taiwan National Health Insurance Research Database of the National Health Research Institute, we identified AMI patients and performed multiple regression analyses to explore the relationships among the different hospital levels and treatment factors. We identified 2942 patients with AMI in medical centers and 4325 patients with AMI in regional hospitals. Cardiologist service volume, performing PCI and medical costs per patient were higher in medical centers than in regional hospitals (P < 0.0001). However, the two hospital levels did not differ significantly in in-hospital mortality (P = 0.1557). Post hoc analysis showed significant differences in in-hospital mortality rate and in medical costs among the eight groups subdivided on the basis of hospital level, cardiologist service volume, and whether PCI was performed (P < 0.001 and P = 0.001, respectively). These results highlight the importance of encouraging hospitals to develop PCI capability and increase their cardiologist service volume after taking medical costs into account. Transferring AMI patients to hospitals with higher cardiologist service volume and PCI performed can also be very important. © The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ananthakrishnan, Ganapathy, E-mail: ganapathy.ananthakrishnan@nhs.net; Murray, Lilian, E-mail: Lilian.murray@glasgow.ac.uk; Ritchie, Moira, E-mail: moira.ritchie@ggc.scot.nhs.uk

Purpose. To report 5-year contrast-enhanced magnetic resonance imaging findings of the REST trial recruits who underwent either uterine artery embolization (UAE) or myomectomy. Methods. A total of 157 patients were randomized to UAE or surgery (hysterectomy or myomectomy). Ninety-nine patients who had UAE and eight patients who had myomectomy were analyzed. MRI scans at baseline, 6 months, and 5 years were independently interpreted by two radiologists. Dominant fibroid diameter, uterine volume, total fibroid infarction (complete 100 %, almost complete 90-99 %, partial <90 %), and new fibroid formation were the main parameters assessed and related to the need for reintervention.more » Results. In the UAE group, mean {+-} standard deviation uterine volume was 670 {+-} 503, 422 {+-} 353, and 292 {+-} 287 mL at baseline, 6 months, and 5 years, respectively. Mean dominant fibroid diameter was 7.6 {+-} 3.0, 5.8 {+-} 2.9, and 5 {+-} 2.9 cm at baseline, 6 months, and 5 years. Fibroid infarction at 6 months was complete in 35 % of women, almost complete in 29 %, and partial in 36 %. Need for reintervention was 19, 10, and 33 % in these groups, respectively (p = 0.123). No myomectomy cases had further intervention. At 5 years, the prevalence of new fibroid was 60 % in the myomectomy group and 7 % in the UAE group (p = 0.008). Conclusion. There is a further significant reduction in both uterine volume and dominant fibroid diameter between 6 months and 5 years after UAE. Complete fibroid infarction does not translate into total freedom from a subsequent reintervention. New fibroid formation is significantly higher after myomectomy.« less

MORTALITY AFTER ACUTE MYOCARDIAL INFARCTION IN HOSPITALS THAT DISPROPORTIONATELY TREAT AFRICAN-AMERICANS

PubMed Central

Skinner, Jonathan; Chandra, Amitabh; Staiger, Douglas; Lee, Julie; McClellan, Mark

2006-01-01

Background African-Americans are more likely be seen by physicians with less clinical training or treated at hospitals with deficient times to acute reperfusion therapies. Less is known about differences in health outcomes. This paper compares risk-adjusted mortality following Acute Myocardial Infarction (AMI) between U.S. hospitals with high and low fractions of elderly black AMI patients. Methods and Results A prospective cohort study was performed for fee-for-service Medicare patients hospitalized for AMI during 1997–2001 (N = 1,136,736). Hospitals (N =4289) were classified into approximate deciles depending on the extent to which the hospital served the African-American population. The lowest category (12.5 percent of AMI patients) included hospitals without any African-American AMI admissions during 1997–2001. Decile 10 (10 percent of AMI patients) included hospitals with the highest fraction of black AMI patients (33.6 percent). The main outcome measures were 90-day and 30-day mortality following AMI. Patients admitted to hospitals disproportionately serving African-Americans experienced no greater level of morbidities or severity of the infarction. Yet hospitals in Decile 10 experienced risk-adjusted 90-day mortality rate of 23.7 percent (95% CI: 23.2–24.2) compared to 20.1 percent (95% CI: 19.7–20.4) in Decile 1 hospitals. Differences in outcomes between hospitals were not explained by income, hospital ownership status, hospital volume, Census region, urban status, or hospital surgical treatment intensity. Conclusions Risk-adjusted mortality following AMI is significantly higher in U.S. hospitals that disproportionately serve African-Americans. A reduction in overall mortality at these hospitals could reduce dramatically black-white disparities in health care outcomes. PMID:16246963

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

PubMed

Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

2005-01-01

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

Predictors of Left Ventricular Remodeling After Myocardial Infarction in Patients With a Patent Infarct Related Coronary Artery After Percutaneous Coronary Intervention (from the Post-Myocardial Infarction Remodeling Prevention Therapy [PRomPT] Trial).

PubMed

Garber, Leonid; McAndrew, Thomas C; Chung, Eugene S; Stancak, Branislav; Svendsen, Jesper H; Monteiro, Joao; Fischer, Trent M; Kueffer, Fred; Ryan, Thomas; Bax, Jeroen; Leon, Angel R; Stone, Gregg W

2018-06-01

Left ventricular (LV) remodeling after myocardial infarction (MI) is a strong predictor of heart failure and mortality. The predictors of long-term remodeling after MI have been incompletely studied. We therefore examined the correlates of LV remodeling in patients with large ST-segment elevation myocardial infarction and a patent infarct artery after percutaneous 2coronary intervention (PCI) from the randomized Post-Myocardial Infarction Remodeling Prevention Therapy trial. Peri-infarct pacing had a neutral effect on long-term remodeling in patients with large first MI. The present analysis includes 109 patients in whom an open artery was restored after PCI, and in whom LV end-diastolic volume (LVEDV) at baseline and 18 months was assessed by transthoracic echocardiography. Multivariable models were fit to identify the independent predictors of LVEDV at baseline and 18 months. By multivariable analysis, male sex (p = 0.004) and anterior MI location (p = 0.03) were independently associated with baseline LVEDV. The following variables were independent predictors of increased LVEDV at 18 months: younger age (p = 0.01), male sex (p = 0.03), peak creatine phosphokinase (p = 0.03), shorter time from MI to baseline transthoracic echocardiography (p = 0.04), baseline LVEDV (p < 0.0001), and lack of statin use (p = 0.03). In conclusion, patients with large MI and an open infarct artery after PCI, anterior MI location, and male sex were associated with greater baseline LVEDV, but MI location was not associated with 18-month LVEDV. In contrast, younger age, peak creatine phosphokinase, male sex, baseline LVEDV, and lack of statin use were associated with long-term LV remodeling. Copyright © 2018 Elsevier Inc. All rights reserved.

Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats.

PubMed

Chen, Yue-Feng; Weltman, Nathan Y; Li, Xiang; Youmans, Steven; Krause, David; Gerdes, Anthony Martin

2013-02-14

Left ventricular (LV) remodeling following large transmural myocardial infarction (MI) remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs) have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear. MI was produced in adult female Sprague-Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study. T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 μm) proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2) expression and tissue inhibitor of metalloproteinases (TIMPs) -1 to -4 expression was also observed in T4 treated MI rats. These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.

Assessment of left atrial volume and function: a comparative study between echocardiography, magnetic resonance imaging and multi slice computed tomography.

PubMed

Kühl, J Tobias; Lønborg, Jacob; Fuchs, Andreas; Andersen, Mads J; Vejlstrup, Niels; Kelbæk, Henning; Engstrøm, Thomas; Møller, Jacob E; Kofoed, Klaus F

2012-06-01

Measurement of left atrial (LA) maximal volume (LA(max)) using two-dimensional transthoracic echocardiography (TTE) provides prognostic information in several cardiac diseases. However, the relationship between LA(max) and LA function is poorly understood and TTE is less well suited for measuring dynamic LA volume changes. Conversely, cardiac magnetic resonance imaging (CMR) and multi-slice computed tomography (MSCT) appears more appropriate for such measures. We sought to determine the relationship between LA size assessed with TTE and LA size and function assessed with CMR and MSCT. Fifty-four patients were examined 3 months post myocardial infarction with echocardiography, CMR and MSCT. Left atrial volumes and LA reservoir function were assessed by TTE. LA time-volume curves were determined and LA reservoir function (cyclic change and fractional change), passive emptying function (reservoir volume) and pump function (left atrial ejection fraction-LAEF) were derived using CMR and MSCT. Left atrial fractional change and left atrial ejection fraction (LAEF) determined with CMR and MSCT were unrelated to LA(max) enlargement by echocardiography (P = NS). There was an overall good agreement between CMR and MSCT, with a small to moderate bias in LA(max) (4.9 ± 10.4 ml), CC (3.1 ± 9.1 ml) and reservoir volume (3.4 ± 9.1 ml). TTE underestimates LA(max) with up to 32% compared with CMR and MSCT (P < 0.001). Left atrial function assessed with MSCT and CMR as LA fractional change and LAEF is not significantly related to LA(max) measured by TTE. TTE systematically underestimated LA volumes, whereas there are good agreements between MSCT and CMR for volumetric and functional properties.

Segmentation of Hyperacute Cerebral Infarcts Based on Sparse Representation of Diffusion Weighted Imaging.

PubMed

Zhang, Xiaodong; Jing, Shasha; Gao, Peiyi; Xue, Jing; Su, Lu; Li, Weiping; Ren, Lijie; Hu, Qingmao

2016-01-01

Segmentation of infarcts at hyperacute stage is challenging as they exhibit substantial variability which may even be hard for experts to delineate manually. In this paper, a sparse representation based classification method is explored. For each patient, four volumetric data items including three volumes of diffusion weighted imaging and a computed asymmetry map are employed to extract patch features which are then fed to dictionary learning and classification based on sparse representation. Elastic net is adopted to replace the traditional L 0 -norm/ L 1 -norm constraints on sparse representation to stabilize sparse code. To decrease computation cost and to reduce false positives, regions-of-interest are determined to confine candidate infarct voxels. The proposed method has been validated on 98 consecutive patients recruited within 6 hours from onset. It is shown that the proposed method could handle well infarcts with intensity variability and ill-defined edges to yield significantly higher Dice coefficient (0.755 ± 0.118) than the other two methods and their enhanced versions by confining their segmentations within the regions-of-interest (average Dice coefficient less than 0.610). The proposed method could provide a potential tool to quantify infarcts from diffusion weighted imaging at hyperacute stage with accuracy and speed to assist the decision making especially for thrombolytic therapy.

Ginsenoside Rg1 nanoparticle penetrating the blood-brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction.

PubMed

Shen, Junyi; Zhao, Zhiming; Shang, Wei; Liu, Chunli; Zhang, Beibei; Zhao, Lingjie; Cai, Hui

2017-01-01

Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood-brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction.

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

PubMed Central

Shen, Junyi; Zhao, Zhiming; Shang, Wei; Liu, Chunli; Zhang, Beibei; Zhao, Lingjie; Cai, Hui

2017-01-01

Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood–brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction. PMID:28919749

Opposite effects of the gap junction blocker octanol on focal cerebral ischemia occluded for different durations.

PubMed

Ding, Wenting; Zhou, Lequan; Liu, Wei; Guan, Li; Li, Xiaoying; Liu, Haimei; Yan, Fuman; Xu, Jinwen; Zeng, Weiyong; Qiu, Min

2014-06-01

Protectants and executioners have been demonstrated to be used by gap junctions in focal cerebral ischemia. Certain researchers hypothesized that the opposite role of gap junctions may be associated with the injury extent, which has been demonstrated to be highly correlated with occlusion duration. In order to examine this hypothesis directly, the effects of octanol, a frequently used drug, were examined to investigate the role of gap junctions, in rats following middle cerebral artery occlusion (MCAO) for 30 min/2 h and 24 h reperfusion, respectively. Octanol significantly reduced the infarct volume following 2 h of occlusion concomitant with lower neurological deficits, whereas it enlarged the infarct volume following 30 min of occlusion. Consistently, octanol attenuated the number of transferase dUTP nick-end labeling (TUNEL) positive neurons in the hippocampal CA1 region following 2 h of occlusion, while opposite effects were observed for 30 min of occlusion. Further immunohistochemical studies demonstrated that the expression of B-cell leukemia-2 (Bcl-2, anti-apoptotic protein) was upregulated and that Bcl-2-associated X (Bax, proapoptotic protein) was downregulated following 2 h of occlusion in the octanol group compared with the ischemic group. Conversely, octanol downregulated the expression of the Bcl-2 protein concomitant with increased Bax protein following 30 min of occlusion. These results indicated that the gap junction blocker octanol can protect against ischemic injury following long-term occlusion, however, can aggravate ischemic injury following short-term occlusion.

Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation.

PubMed

Huang, Y C; Tzeng, W S; Wang, C C; Cheng, B C; Chang, Y K; Chen, H H; Lin, P C; Huang, T Y; Chuang, T J; Lin, J W; Chang, C P

2013-09-01

This study aimed to further investigate the effects of agmatine on brain edema in the rats with middle cerebral artery occlusion (MCAO) injury using magnetic resonance imaging (MRI) monitoring and biochemical and histopathologic evaluation. Following surgical induction of MCAO for 90min, agmatine was injected 5min after beginning of reperfusion and again once daily for the next 3 post-operative days. The events during ischemia and reperfusion were investigated by T2-weighted images (T2WI), serial diffusion-weighted images (DWI), calculated apparent diffusion coefficient (ADC) maps and contrast-enhanced T1-weighted images (CE-T1WI) during 3h-72h in a 1.5T Siemens MAGNETON Avanto Scanner. Lesion volumes were analyzed in a blinded and randomized manner. Triphenyltetrazolium chloride (TTC), Nissl, and Evans Blue stainings were performed at the corresponding sections. Increased lesion volumes derived from T2WI, DWI, ADC, CE-T1WI, and TTC all were noted at 3h and peaked at 24h-48h after MCAO injury. TTC-derived infarct volumes were not significantly different from the T2WI, DWI-, and CE-T1WI-derived lesion volumes at the last imaging time (72h) point except for significantly smaller ADC lesions in the MCAO model (P<0.05). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived on T2WI, DWI or CE-T1WI than ADC (P<0.05). At the last imaging time point, a significant increase in Evans Blue extravasation and a significant decrease in Nissl-positive cells numbers were noted in the vehicle-treated MCAO injured animals. The lesion volumes derived from T2WI, DWI, CE-T1WI, and Evans blue extravasation as well as the reduced numbers of Nissl-positive cells were all significantly attenuated in the agmatine-treated rats compared with the control ischemia rats (P<0.05). Our results suggest that agmatine has neuroprotective effects against brain edema on a reperfusion model after transient cerebral ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

Infarction of Uterine Fibroids After Embolization: Relationship Between Postprocedural Enhanced MRI Findings and Long-Term Clinical Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katsumori, Tetsuya, E-mail: katsumo@eurus.dti.ne.jp; Kasahara, Toshiyuki; Kin, Yoko

2008-01-15

Purpose. To retrospectively evaluate the relationship between the degree of infarction of uterine fibroids on enhanced MRI after embolization and long-term clinical outcomes. Methods. During 92 months, 290 consecutive patients with symptomatic uterine fibroids were treated with embolization; 221 who underwent enhanced MRI before embolization and 1 week after embolization were included in this study. The infarction rates of all fibroid tissue were assessed using enhanced MRI after embolization. Patients were divided into three groups according to the infarction rates: group A (100% infarction, n 142), group B (90-99% infarction, n = 74), group C (<90% infarction, n = 5).more » The cumulative rates of clinical outcomes were compared among groups using the Kaplan-Meier limited method. Results. Group A had a significantly higher rate of symptom control than groups B and C. The cumulative rates of symptom control at 5 years were 93%, 71%, and 60% in groups A, B, and C, respectively. Group A had a significantly lower rate of gynecologic intervention after embolization than groups B and C. The cumulative rates of additional gynecologic intervention at 5 years were 3%, 15%, and 20% in groups A, B, and C, respectively. Conclusions. The degree of infarction of uterine fibroids after embolization on enhanced MRI was related to long-term clinical outcomes. Complete infarction of all fibroid tissue can induce a higher rate of symptom control, with a lower rate of additional gynecologic intervention in the long term compared with incomplete infarction of fibroid tissue.« less

Dysphagia in supratentorial recent small subcortical infarcts results from bilateral pyramidal tract damage.

PubMed

Fandler, Simon; Gattringer, Thomas; Pinter, Daniela; Pirpamer, Lukas; Borsodi, Florian; Eppinger, Sebastian; Niederkorn, Kurt; Enzinger, Christian; Fazekas, Franz

2018-01-01

Background Dysphagia occurs in up to 20% of patients with a recent small subcortical infarct, even when excluding brainstem infarcts. Aim To examine the impact of lesion topography and concomitant cerebrovascular lesions on the occurrence of dysphagia in patients with a single supratentorial recent small subcortical infarct. Methods We retrospectively identified all inpatients with magnetic resonance imaging-confirmed supratentorial recent small subcortical infarcts over a five-year period. Dysphagia was determined by speech-language therapists. Recent small subcortical infarcts were compiled into a standard brain model and compared using lesion probability maps. Furthermore, magnetic resonance imaging scans were reviewed for the combination of both acute and old cerebrovascular lesions. Results A total of 243 patients with a recent small subcortical infarct were identified (mean age 67.9 ± 12.2 years). Of those, 29 had mild and 18 moderate-to-severe dysphagia. Lesion probability maps suggested no recent small subcortical infarct location favoring the occurrence of moderate-to-severe dysphagia. However, patients with moderate-to-severe dysphagia more frequently showed combined damage to both pyramidal tracts by the recent small subcortical infarct and a contralateral old lesion (lacune: 77.8% vs. 19.9%, p < 0.001; lacune or confluent white matter hyperintensities: 100% vs. 57.7%, p < 0.001) than patients without swallowing dysfunction. Comparable results were obtained when analyzing patients with any degree of dysphagia. Conclusions Preexisting contralateral vascular pyramidal tract lesions are closely related to the occurrence of moderate-to-severe dysphagia in patients with supratentorial recent small subcortical infarcts.

Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis.

PubMed

Kleinschnitz, Christoph; Braeuninger, Stefan; Pham, Mirko; Austinat, Madeleine; Nölte, Ingo; Renné, Thomas; Nieswandt, Bernhard; Bendszus, Martin; Stoll, Guido

2008-04-01

Models of photochemically-induced thrombosis are widely used in cerebrovascular research. Photothrombotic brain infarctions can be induced by systemic application of photosensitizing dyes followed by focal illumination of the cerebral cortex. Although the ensuing activation of platelets is well established, their contribution for thrombosis and tissue damage has not formally been proved. Infarction to the cerebral cortex was induced in mice by Rose Bengal and a cold light source. To assess the functional role of platelets, animals were platelet-depleted by anti-GPIbalpha antibodies or treated with GPIIb/IIIa-blocking F(ab)(2) fragments. The significance of the plasmatic coagulation cascade was determined by using blood coagulation factor XII (FXII)-deficient mice or heparin. Infarct development and infarct volumes were determined by serial MRI and conventional and electron microscopy. There was no difference in development and final size of photothrombotic infarctions in mice with impaired platelet function. Moreover, deficiency of FXII, which initiates the intrinsic pathway of coagulation and is essential for thrombus formation, or blockade of FXa, the key protease during the waterfall cascade of plasmatic coagulation, by heparin likewise did not affect lesion development. Our data demonstrate that platelet activation, factor XII-driven thrombus formation, and plasmatic coagulation pathways downstream of FX are not a prerequisite for ensuing tissue damage in models of photothrombotic vessel injury indicating that other pathomechanisms are involved. We suggest that this widely used model does not depend on platelet- or plasmatic coagulation-derived thrombosis.

Optimization of behavioural tests for the prediction of outcomes in mouse models of focal middle cerebral artery occlusion.

PubMed

Wen, Zhuoyu; Xu, Xiaomeng; Xu, Lili; Yang, Lian; Xu, Xiaohui; Zhu, Juehua; Wu, Li; Jiang, Yongjun; Liu, Xinfeng

2017-06-15

Intraluminal middle cerebral artery occlusion (MCAO) is the most widely used model of stroke. We aimed to predict the outcome of MCAO using a combination of fine behavioural tests for the prediction of unsuccessful surgery in mice leading to no infarction, haemorrhage and unexpected death. MCAO was performed on adult mice under the guidance of laser-Doppler flowmetry (LDF) to warrant a decrease in regional cerebral blood flow (rCBF) in the MCA territory. Four outcomes of MCAO were defined according to histological analysis: infarction, no infarction, haemorrhage and unexpected death (death within 24h post-surgery). Fine behavioural tests including the rotarod, modified neurological severity score (mNSS), Clark general and Clark focal tests were performed separately at 6h, 12h and 24h post-stroke. A total of 94 mice were included in the analysis. The infarction rate associated with MCAO was 58.5% (55/94). After optimization of the timing and behavioural tests, we found that higher Clark focal (>17.5) or higher mNSS scores (>10) were markedly related to early death, whereas a lower mNSS score (<3.5) was indicative of a tendency to show no infarction at 6h post-stroke. After 24h post-stroke, there was a positive correlation between the infarct volume and Clark focal results. Behavioural tests could help to predict the outcomes in the MCAO mouse model. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Imaging characteristics and pathogenesis of intracranial artery stenosis in patients with acute cerebral infarction

PubMed Central

Xu, Wenyuan; Xie, Ning; Zhang, Cheng; Huang, Qin

2018-01-01

The current study aimed to investigate the imaging characteristics and pathogenesis of intracranial artery stenosis in patients with acute cerebral infarction. In total, 84 patients diagnosed with acute cerebral infarction were recruited. Magnetic resonance angiography was performed to detect the existence of intracranial artery stenosis or occlusion. In addition, magnetic resonance imaging and diffusion weighted imaging were employed to analyze the infarction types and characteristics. In the majority of patients, the infarction resulted from internal carotid stenosis (77 cases; 91.7%), while it was caused by vertebral artery stenosis in a small number of cases (7 cases; 8.3%). Multiple infarction was identified the most common type of infarction among all cases (69.0%). The most common types of infarctions in the internal carotid system were multiple infarction implicating both the cortex and centrum ovale (23.4%), and internal watershed infarction (22.1%). Although the number of cases was relatively small, multiple infarction was observed to have a high incidence in the vertebral artery system. Bedside electrocardiogram was also recorded to determine the sinus rhythm and examine the abnormal hemodynamics. The sinus bradycardia rate of patients with multiple infarction was markedly greater in comparison with that in single infarction patients (χ2=0.01, P<0.05). Transcranial Doppler plus microembolus monitoring was utilized to explore the possible pathogenesis of all types of infarctions, such as arterial embolization. As compared with the single infarction patients, the embolus rate in patients with multiple infarction was notably increased by ~3.7-fold (χ2=8.65, P<0.05). In conclusion, the cerebral infarction was common in the internal carotid system, with multiple infarction observed in the majority of cases. The pathogenesis of cerebral infarction included arterial embolization and inadequate hemoperfusion. PMID:29725389

[Segmental wall movement of the left ventricle in healthy persons and myocardial infarct patients studied by a catheter-less nuclear medical method (camera-cinematography of the heart)].

PubMed

Geffers, H; Sigel, H; Bitter, F; Kampmann, H; Stauch, M; Adam, W E

1976-08-01

Camera-Kinematography is a nearly noninvasive method to investigate regional motion of the myocard, and allows evaluation of the function of the heart. About 20 min after injection of 15-20 mCi of 99mTC-Human-Serum-Albumin, when the tracer is distributed homogenously within the bloodpool, data acquisition starts. Myocardial wall motion is represented in an appropriate quasi three-dimensional form. In this representation scars can be revealed as "silent" (akinetic) regions, aneurysms by asynchronic motion. Time activity curves for arbitrarily chosen regions can be calculated and give an equivalent for regional volume changes. 16 patients with an old infarction have been investigated. In fourteen cases the location and extent of regions with abnormal motion could be evaluated. Only two cases of a small posterior wall infarction did not show deviations from normal contraction pattern.

[Factors influencing the effectiveness of physical rehabilitation after myocardial infarction].

PubMed

Sumin, A N; Beresneva, V L; Enina, T N; Verkhoshapova, T N; Kabova, E A; Valeeva, V I; Shapaurina, N V

2007-01-01

The aim of the study was to compare initial clinical, hemodynamic, and vegetative parameters in patients with myocardial infarction (MI) who had undergone physical rehabilitation with different results. The subjects were 106 male patients aged 48.6 +/- 0.95 years undergoing sanatorium rehabilitation after MI. According to the dynamics of exercise tolerance (ET) during the course of treatment, the subjects were divided into three groups: group one consisted of 39 patients with a significant ET growth of more than 10W, group two consisted of 47 patients with no changes in ET or its insignificant growth of less than 10W, and group three consisted of 20 patients with a decrease in ET revealed during a repeated test. In group three patients, the initial EchoCG examination revealed a higher degree of myocardial lesion, which was manifested by lowered ejection fraction and sphericity index, increased end-diastolic volume, and increased degree of left ventricular (LV) asynergy. Furthermore, day-time ventricular extrasystoles were more frequent in these patients; the number of patients with large-focal MI, LV aneurysm, and post-infarction stenocardia was also higher in group three. Correlation and multiple step regression analysis revealed that both initial parameters of vegetative nervous system, data from initial load test, and the EchoCG measurements of the right atrium were associated with the degree of ET growth according to VEM results. The data from the study are able to help individualize rehabilitation of MI patients, especially those with severe myocardial lesion.

Electroacupuncture ameliorating post-stroke cognitive impairments via inhibition of peri-infarct astroglial and microglial/macrophage P2 purinoceptors-mediated neuroinflammation and hyperplasia.

PubMed

Huang, Jia; You, Xiaofang; Liu, Weilin; Song, Changming; Lin, Xiaomin; Zhang, Xiufeng; Tao, Jing; Chen, Lidian

2017-10-10

During ischemic stroke (IS), adenosine 5'-triphosphate (ATP) is released from damaged nerve cells of the infract core region to the extracellular space, invoking peri-infarct glial cellular P2 purinoceptors singling, and causing pro-inflammatory cytokine secretion, which is likely to initiate or aggravate motor and cognitive impairment. It has been proved that electroacupuncture (EA) is an effective and safe strategy used in anti-inflammation. However, EA for the role of purine receptors in the central nervous system has not yet been reported. Ischemia-reperfusion injured rat model was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). EA treatment at the DU 20 and DU 24 acupoints treatment were conducted to rats from the 12 h after MCAO/R injury for consecutive 7 days. The neurological outcomes, infarction volumes and the level of astroglial and microglial/macrophage hyperplasia, inflammatory cytokine and P2X7R and P2Y1R expression in the peri-infarct hippocampal CA1and sensorimotor cortex were investigated after IS to evaluate the MCAO/R model and therapeutic mechanism of EA treatment. EA effectively reduced the level of pro-inflammatory cytokine interleukin-1β (IL-1β) as evidenced by reduction in astroglial and microglial/macrophage hyperplasia and the levels of P2X7R and ED1, P2X7R and GFAP, P2Y1R and ED1, P2Y1R and GFAP co-expression in peri-infarct hippocampal CA1 and sensorimotor cortex compared with that of MCAO/R model and Non-EA treatment, accompanied by the improved neurological deficit and the motor and memory impairment outcomes. Therefore, our data support the hypothesis that EA could exert its anti-inflammatory effect via inhibiting the astroglial and microglial/macrophage P2 purinoceptors (P2X7R and P2Y1R)-mediated neuroinflammation after MCAO/R injury. Astroglial and microglial/macrophage P2 purinoceptors-mediated neuroinflammation and hyperplasia in peri-infarct hippocampal CA1 and sensorimotor cortex were attenuated by EA treatment after ischemic stroke accompanied by the improved motor and memory behavior performance.

Reverse left ventricular remodeling after acute myocardial infarction: the prognostic impact of left ventricular global torsion.

PubMed

Spinelli, Letizia; Morisco, Carmine; Assante di Panzillo, Emiliano; Izzo, Raffaele; Trimarco, Bruno

2013-04-01

Reverse left ventricular (LV) remodeling (>10 % reduction in LV end-systolic volume) may occur in patients recovering for acute ST-elevation myocardial infarction (STEMI), undergoing percutaneous revascularization of infarct-related coronary artery (PCI). To detect whether LV global torsion obtained by two-dimensional speckle-tracking echocardiography was predictive of reverse LV remodeling, 75 patients with first anterior wall STEMI were studied before (T1) and after PCI (T2) and at 6-month follow-up. Two-year clinical follow-up was also accomplished. LV volumes and both LV sphericity index and conic index were obtained by three-dimensional echocardiography. Reverse remodeling was observed in 25 patients (33 %). By multivariate analysis, independent predictors of reverse LV remodeling were: LV conic index, T2 LV torsion and Δ torsion (difference between T2 and T1 LV torsion expressed as percentage of this latter). According to receiver operating characteristic analysis, 1.34°/cm for T2 LV torsion (sensitivity 88 % and specificity 80 %) and 54 % for Δ torsion (sensitivity 92 % and specificity 82 %) were the optimal cutoff values in predicting reverse LV remodeling. In up to 24 month follow-up, 4 non-fatal re-infarction, 7 hospitalization for heart failure and 4 cardiac deaths occurred. By multivariate Cox analysis, the best variable significantly associated with event-free survival rate was reverse LV remodeling with a hazard ratio = 9.9 (95 % confidence interval, 7.9-31.4, p < 0.01). In conclusion, reverse LV remodeling occurring after anterior wall STEMI is associated with favorable long-term outcome. The improvement of global LV torsion following coronary artery revascularization is the major predictor of reverse LV remodeling.

Protective Effect of Ad-VEGF-Bone Mesenchymal Stem Cells on Cerebral Infarction.

PubMed

Chen, Bo; Zhang, Feng; Li, Qiao-Yu; Gong, Aihua; Lan, Qing

2016-01-01

To understand the mechanism of intracerebroventricular transplantation of vascular endothelial growth factor (VEGF) genemodified bone mesenchymal stem cells (BMSCs) in rats after cerebral infarction. The middle cerebral artery occlusion ischemia/reperfusion (MCAO I/R) model was established in rats using the Zea-Longa suture method. A recombinant adenovirus (Ad-VEGF) was engineered to express VEGF. The rats were divided into 3 groups. Control BMSC infected with control adenovirus (BMSC-Ad), BMSC infected by Ad-VEGF (BMSC-Ad-VEGF), and phosphate buffered saline (PBS) suspension were injected into the intracerebroventricular system of the rats in groups 1, 2 and 3 respectively, 24 hours after middle cerebral artery occlusion (MCAO). The neurological function of rats was evaluated with the modified Neurological Severity Scores (mNSS). The infarct volume of brain in rats was determined using 2,3,5-triphenyltetrazolium chloride (TTC) stain at 14 days. GFAP and pGSK3β expression of ischemic penumbra was determined using immunohistochemical method. GFAP, pAKT, AKT, and pGSK3β expressions were determined with Western blot. Functional improvement was accelerated in animals receiving BMSC-Ad, while improvement at all times between 7 days and 28 days post MCAO was significantly greater in animals transplanted with BMSC-Ad-VEGF than for other treated animals. The number of GFAP-labeled cells was prevented by post-ischemic BMSC-Ad-VEGF treatment; pMCAO activate the PI3K/AKT/GSK3β pathway to reduce reactive gliosis. Our findings demonstrate that PI3K/AKT/GSK3β pathway could reduce reactive gliosis, ameliorate neurological deficit, diminish the percentage of cerebral infarction volume in rats, and facilitate angiogenesis.

Splenic release of platelets contributes to increased circulating platelet size and inflammation after myocardial infarction.

PubMed

Gao, Xiao-Ming; Moore, Xiao-Lei; Liu, Yang; Wang, Xin-Yu; Han, Li-Ping; Su, Yidan; Tsai, Alan; Xu, Qi; Zhang, Ming; Lambert, Gavin W; Kiriazis, Helen; Gao, Wei; Dart, Anthony M; Du, Xiao-Jun

2016-07-01

Acute myocardial infarction (AMI) is characterized by a rapid increase in circulating platelet size but the mechanism for this is unclear. Large platelets are hyperactive and associated with adverse clinical outcomes. We determined mean platelet volume (MPV) and platelet-monocyte conjugation (PMC) using blood samples from patients, and blood and the spleen from mice with AMI. We further measured changes in platelet size, PMC, cardiac and splenic contents of platelets and leucocyte infiltration into the mouse heart. In AMI patients, circulating MPV and PMC increased at 1-3 h post-MI and MPV returned to reference levels within 24 h after admission. In mice with MI, increases in platelet size and PMC became evident within 12 h and were sustained up to 72 h. Splenic platelets are bigger than circulating platelets in normal or infarct mice. At 24 h post-MI, splenic platelet storage was halved whereas cardiac platelets increased by 4-fold. Splenectomy attenuated all changes observed in the blood, reduced leucocyte and platelet accumulation in the infarct myocardium, limited infarct size and alleviated cardiac dilatation and dysfunction. AMI-induced elevated circulating levels of adenosine diphosphate and catecholamines in both human and the mouse, which may trigger splenic platelet release. Pharmacological inhibition of angiotensin-converting enzyme, β1-adrenergic receptor or platelet P2Y12 receptor reduced platelet abundance in the murine infarct myocardium albeit having diverse effects on platelet size and PMC. In conclusion, AMI evokes release of splenic platelets, which contributes to the increase in platelet size and PMC and facilitates myocardial accumulation of platelets and leucocytes, thereby promoting post-infarct inflammation. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Spatiotemporal characterization of brain infarction by sequential multimodal MR imaging following transient focal ischemia in a Rat model of intra-arterial middle cerebral artery occlusion.

PubMed

Gory, Benjamin; Chauveau, Fabien; Bolbos, Radu; Langlois, Jean-Baptiste; Labeyrie, Paul-Emile; Signorelli, Francesco; Turjman, Alexis; Turjman, Francis

2016-12-01

To assess spatiotemporal brain infarction evolution by sequential multimodal magnetic resonance (MR) imaging in an endovascular model of acute stroke in rats. A microwire was selectively placed in the middle cerebral artery (MCA) in 16 consecutives rats during 90 minutes occlusion. Longitudinal 7-T MR imaging, including angiography, diffusion, and perfusion was performed during ischemia, immediately after reperfusion, 3 h and 24 h after subsequent reperfusion. MCA occlusion was complete in 75 % and partial in 18.7 %. Hypoperfusion (mean ± SD) was observed in all animals during ischemia (-59 ± 18 % of contralateral hemisphere, area 31 ± 5 mm 2 ). Infarction volume (mean ± SD) was 90 ± 64 mm 3 during ischemia and 57 ± 67 mm 3 at 24 h. Brain infarction was fronto-parietal cortical in five animals (31 %), striatal in four animals (25 %), and cortico-striatal in seven animals (44 %) at 24 h. All rats survived at 24 h. This model is suitable to neuroprotection studies because of possible acute and close characterization of spatiotemporal evolution of brain infarction by MR imaging techniques, and evidence of ischemic penumbra, the target of neuroprotection agents. However, optimization of the brain infarct reproducibility needs further technical and neurointerventional tools improvements. • Nitinol microwire is MRI compatible allowing spatiotemporal characterization of brain infarction in rats. • Microwire selective placement in middle cerebral artery allows complete artery occlusion in 75 %. • A diffusion/perfusion mismatch during arterial occlusion is observed in 77 % of rats.

A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance: experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data.

PubMed

Engblom, Henrik; Tufvesson, Jane; Jablonowski, Robert; Carlsson, Marcus; Aletras, Anthony H; Hoffmann, Pavel; Jacquier, Alexis; Kober, Frank; Metzler, Bernhard; Erlinge, David; Atar, Dan; Arheden, Håkan; Heiberg, Einar

2016-05-04

Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) using magnitude inversion recovery (IR) or phase sensitive inversion recovery (PSIR) has become clinical standard for assessment of myocardial infarction (MI). However, there is no clinical standard for quantification of MI even though multiple methods have been proposed. Simple thresholds have yielded varying results and advanced algorithms have only been validated in single center studies. Therefore, the aim of this study was to develop an automatic algorithm for MI quantification in IR and PSIR LGE images and to validate the new algorithm experimentally and compare it to expert delineations in multi-center, multi-vendor patient data. The new automatic algorithm, EWA (Expectation Maximization, weighted intensity, a priori information), was implemented using an intensity threshold by Expectation Maximization (EM) and a weighted summation to account for partial volume effects. The EWA algorithm was validated in-vivo against triphenyltetrazolium-chloride (TTC) staining (n = 7 pigs with paired IR and PSIR images) and against ex-vivo high resolution T1-weighted images (n = 23 IR and n = 13 PSIR images). The EWA algorithm was also compared to expert delineation in 124 patients from multi-center, multi-vendor clinical trials 2-6 days following first time ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) (n = 124 IR and n = 49 PSIR images). Infarct size by the EWA algorithm in vivo in pigs showed a bias to ex-vivo TTC of -1 ± 4%LVM (R = 0.84) in IR and -2 ± 3%LVM (R = 0.92) in PSIR images and a bias to ex-vivo T1-weighted images of 0 ± 4%LVM (R = 0.94) in IR and 0 ± 5%LVM (R = 0.79) in PSIR images. In multi-center patient studies, infarct size by the EWA algorithm showed a bias to expert delineation of -2 ± 6 %LVM (R = 0.81) in IR images (n = 124) and 0 ± 5%LVM (R = 0.89) in PSIR images (n = 49). The EWA algorithm was validated experimentally and in patient data with a low bias in both IR and PSIR LGE images. Thus, the use of EM and a weighted intensity as in the EWA algorithm, may serve as a clinical standard for the quantification of myocardial infarction in LGE CMR images. CHILL-MI: NCT01379261 . NCT01374321 .

Gene Therapy With Angiotensin-(1-9) Preserves Left Ventricular Systolic Function After Myocardial Infarction.

PubMed

Fattah, Caroline; Nather, Katrin; McCarroll, Charlotte S; Hortigon-Vinagre, Maria P; Zamora, Victor; Flores-Munoz, Monica; McArthur, Lisa; Zentilin, Lorena; Giacca, Mauro; Touyz, Rhian M; Smith, Godfrey L; Loughrey, Christopher M; Nicklin, Stuart A

2016-12-20

Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin-angiotensin-aldosterone system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic mini-pump. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI). The authors evaluated effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post-infarction. C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular pressure volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation/contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff-perfused whole-heart model. Gene delivery of Ang-(1-9) reduced sudden cardiac death post-MI. Pressure volume measurements revealed complete restoration of end-systolic pressure, ejection fraction, end-systolic volume, and the end-diastolic pressure volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism. Our novel findings showed that Ang-(1-9) gene therapy preserved left ventricular systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) directly affected cardiomyocyte calcium handling through a protein kinase A-dependent mechanism. These data emphasized Ang-(1-9) gene therapy as a potential new strategy in the context of MI. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluation of left ventricular wall motion and function in patients with previous myocardial infarction by three-dimensional 99mTc-HSAD multigated cardiac pool imaging.

PubMed

Yamazaki, J; Naitou, K; Ishida, S; Uno, N; Saisho, K; Munakata, T; Morishita, T; Takano, M; Yabe, Y

1997-05-01

To evaluate left ventricular (LV) wall motion stereoscopically from all directions and to calculate the LV volume by three-dimensional (3D) imaging. 99mTc-DTPA human serum albumin-multigated cardiac pool-single photon emission computed tomography (99mTc-MUGA-SPECT) was performed. A new data processing program was developed with the Application Visualization System-Medical Viewer (AVS-MV) based on images obtained from 99mTc-MUGA-SPECT. In patients with previous myocardial infarction, LV function and LV wall motion were evaluated by 3D-99mTc-MUGA imaging. The LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were obtained from 3D-99mTc-MUGA images by the surface rendering method, and the left ventricular ejection fraction (LVEF) was calculated at thresholds of 35% (T1), 40% (T2), 45% (T3), and 50% (T4). There was a strong correlation between the LV volume calculated by 3D-99mTc-MUGA imaging at a threshold of 40% and that determined by contrast left ventriculography (LVEDV: 194.7 +/- 36.0 ml vs. 198.7 +/- 39.1 ml, r = 0.791, p < 0.001; LVESV: 91.6 +/- 44.5 ml vs. 93.3 +/- 41.3 ml, r = 0.953, p < 0.001), respectively. When compared with the LVEF data obtained by left ventriculography, significant correlations were found for 3D images reconstructed at each threshold (T1: r = 0.966; T2: r = 0.962; T3: r = 0.958; and T4: r = 0.955). In addition, when LV wall motion obtained by 3D-99mTc-MUGA imaging (LAT and LAO views) was compared with the results obtained by left ventriculography (RAO and LAO views), there was good agreement. 3D-99mTc-MUGA imaging was superior in allowing evaluation of LV wall motion in all directions and in assessment of LV function, since data acquisition and image reconstruction could be done within a short time with the three-detector imaging system and AVS-MV. This method appears to be very useful for the observation of both LV wall motion and LV function in patients with ischemic heart disease, because it is a noninvasive examination.

N-3 Fatty Acid Rich Triglyceride Emulsions Are Neuroprotective after Cerebral Hypoxic-Ischemic Injury in Neonatal Mice

PubMed Central

Vannucci, Susan J.; Mastropietro, Christopher; Bazan, Nicolas G.; Ten, Vadim S.; Deckelbaum, Richard J.

2013-01-01

We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O2 for 15 minutes at 37°C. Intraperitoneal injection with n-3-rich TG emulsions, n-6 rich TG emulsions or saline for control was administered at different time points before and/or after H/I. In separate experiments, dose responses were determined with TG containing only docosahexaenoic acid (Tri-DHA) or eicosapentaenoic acid (Tri-EPA) with a range of 0.1–0.375 g n-3 TG/kg, administered immediately after H/I insult. Infarct volume and cerebral blood flow (CBF) were measured. Treatment with n-3 TG emulsions both before- and after- H/I significantly reduced total infarct volume by a mean of 43% when administered 90 min prior to H/I and by 47% when administered immediately after H/I. In post-H/I experiments Tri-DHA, but not Tri-EPA exhibited neuroprotective effects with both low and high doses (p<0.05). Moreover, delayed post-H/I treatment with Tri-DHA significantly decreased total infarct volume by a mean of 51% when administered at 0 hr, by 46% at 1 hr, and by 51% at 2 hr after H/I insult. No protective effect occurred with Tri-DHA injection at 4 hr after H/I. There were no n-3 TG related differences in CBF. A significant reduction in brain tissue death was maintained after Tri-DHA injection at 8 wk after the initial brain injury. Thus, n-3 TG, specifically containing DHA, is protective against H/I induced brain infarction when administered up to 2 hr after H/I injury. Acute administration of TG-rich DHA may prove effective for treatment of stroke in humans. PMID:23437099

Hyperglycaemia, Insulin Therapy and Critical Penumbral Regions for Prognosis in Acute Stroke: Further Insights from the INSULINFARCT Trial

PubMed Central

Rosso, Charlotte; Pires, Christine; Corvol, Jean-Christophe; Baronnet, Flore; Crozier, Sophie; Leger, Anne; Deltour, Sandrine; Valabregue, Romain; Amor-Sahli, Mélika; Lehéricy, Stéphane; Dormont, Didier; Samson, Yves

2015-01-01

Background Recently, the concept of ‘clinically relevant penumbra’ was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome. Methods We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome. Findings Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10−6mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome. Conclusion These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction. Trial Registration ClinicalTrials.gov NCT00472381 PMID:25793765

Lower age at first myocardial infarction in female compared to male smokers.

PubMed

Bähler, Caroline; Gutzwiller, Felix; Erne, Paul; Radovanovic, Dragana

2012-10-01

Smoking is one of the most important risk factors for myocardial infarction. Smokers usually suffer their first myocardial infarction earlier in life compared to non-smokers. This age difference seems to be greater in women than in men. The aim of this study was to examine the age and sex differences in terms of smoking in patients with first myocardial infarction who were enrolled in the Swiss National Registry of myocardial infarction, AMIS Plus. Data of 15,711 patients admitted to an AMIS Plus hospital between 1999 and 2008 with a first myocardial infarction were analysed. Several multivariate regression, interaction and sensitivity analyses were conducted. The mean age at first myocardial infarction was 68.5 ± 12.2 years for non-smokers and 56.6 ± 11.7 years for smokers (P < 0.001). After stratification by sex the difference between non-smokers and smokers was 10.2 years in men and 13.1 years in women. Even after adjustment for risk factors (overweight, hypertension, dyslipidaemia, diabetes), comorbidities (peripheral vascular disease, cerebrovascular disease, chronic lung disease), regular cardiovascular medication intake before admission, Killip classification and ECG on admission, male smokers were 8.7 years younger than male non-smokers at first myocardial infarction. In women, the age difference between smokers and non-smokers was 10.8 years, giving a sex-specific difference of 2.1 years (P < 0.001). In the AMIS Plus cohort, smoking was associated with younger age at first myocardial infarction and this was much more pronounced in women. Public health campaigns should take into account the impact of smoking on premature first myocardial infarction, especially in women.

Unenhanced MR Angiography of Uterine and Ovarian Arteries after Uterine Artery Embolization: Differences between Patients with Incomplete and Complete Fibroid Infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mori, Kensaku, E-mail: moriken@md.tsukuba.ac.jp; Saida, Tsukasa; Shibuya, Yoko

Purpose: To compare the status of uterine and ovarian arteries after uterine artery embolization (UAE) in patients with incomplete and complete fibroid infarction via unenhanced 3D time-of-flight magnetic resonance (MR) angiography. Materials and Methods: Thirty-five consecutive women (mean age 43 years; range 26-52 years) with symptomatic uterine fibroids underwent UAE and MR imaging before and within 2 months after UAE. The patients were divided into incomplete and complete fibroid infarction groups on the basis of the postprocedural gadolinium-enhanced MR imaging findings. Two independent observers reviewed unenhanced MR angiography before and after UAE to determine bilateral uterine and ovarian arterial flowmore » scores. The total arterial flow scores were calculated by summing the scores of the 4 arteries. All scores were compared with the Mann-Whitney test. Results: Fourteen and 21 patients were assigned to the incomplete and complete fibroid infarction groups, respectively. The total arterial flow score in the incomplete fibroid infarction group was significantly greater than that in the complete fibroid infarction group (P = 0.019 and P = 0.038 for observers 1 and 2, respectively). In 3 patients, additional therapy was recommended for insufficient fibroid infarction. In 1 of the 3 patients, bilateral ovarian arteries were invisible before UAE but seemed enlarged after UAE. Conclusion: The total arterial flow from bilateral uterine and ovarian arteries in patients with incomplete fibroid infarction is less well reduced than in those with complete fibroid infarction. Postprocedural MR angiography provides useful information to estimate the cause of insufficient fibroid infarction in individual cases.« less

Education and the cognitive decline associated with MRI-defined brain infarct.

PubMed

Elkins, J S; Longstreth, W T; Manolio, T A; Newman, A B; Bhadelia, R A; Johnston, S C

2006-08-08

To assess whether educational attainment, a correlate of cognitive reserve, predicts the amount of cognitive decline associated with a new brain infarct. The Cardiovascular Health Study is a population-based, longitudinal study of people aged 65 years and older. Cognitive function was measured annually using the Modified Mini-Mental State Examination (3MS) and the Digit-Symbol Substitution Test (DSST). The authors tested whether education level modified 1) the cross-sectional association between cognitive performance and MRI-defined infarct and 2) the change in cognitive function associated with an incident infarct at a follow-up MRI. In cross-sectional analysis (n = 3,660), MRI-defined infarct was associated with a greater impact on 3MS performance in the lowest education quartile when compared with others (p for heterogeneity = 0.012). Among those with a follow-up MRI who had no infarct on initial MRI (n = 1,433), education level was not associated with the incidence, size, or location of new brain infarct. However, a new MRI-defined infarct predicted substantially greater decline in 3MS scores in the lowest education group compared with the others (6.3, 95% CI 4.4- to 8.2-point decline vs 1.7, 95% CI 0.7- to 2.7-point decline; p for heterogeneity < 0.001). Higher education was not associated with smaller declines in DSST performance in the setting of MRI-defined infarct. Education seems to modify an individual's decline on a test of general cognitive function when there is incident brain infarct. These findings are consistent with the hypothesis that cognitive reserve influences the impact of vascular injury in the brain.

Effect of Elevated Reperfusion Pressure on "No Reflow" Area and Infarct Size in a Porcine Model of Ischemia-Reperfusion.

PubMed

Pantsios, Chris; Kapelios, Chris; Vakrou, Styliani; Diakos, Nikolaos; Pozios, Iraklis; Kontogiannis, Chris; Nanas, John; Malliaras, Konstantinos

2016-07-01

The "no reflow" phenomenon (microvascular obstruction despite restoration of epicardial blood flow) develops postreperfusion in acute myocardial infarction and is associated with poor prognosis. We hypothesized that increased reperfusion pressure may attenuate the no reflow phenomenon, as it could provide adequate flow to overcome the high resistance of the microvasculature within the no reflow zone. Thus, we investigated the effect of modestly elevated blood pressure during reperfusion on the extent of no reflow area and infarct size in a porcine model of ischemia-reperfusion. Eighteen farm pigs underwent acute myocardial infarction by occlusion of the anterior descending coronary artery for 1 hour, followed by 2 hours of reperfusion. Just prior to reperfusion, animals were randomized into 2 groups: in group 1 (control group, n = 9), no intervention was performed. In group 2 (n = 9), aortic pressure was increased by ∼20% (compared to ischemia) by partial clamping of the ascending aorta during reperfusion. Following 2 hours of reperfusion, animals were euthanized to measure area at risk, infarct size, and area of no reflow. Partial clamping of the ascending aorta resulted in modest elevation of blood pressure during reperfusion. The area at risk did not differ between the 2 groups. The no reflow area was significantly increased in group 2 compared to control animals (50% ± 13% vs 37% ± 9% of the area at risk; P = .04). The infarcted area was significantly increased in group 2 compared to control animals (75% ± 17% vs 52% ± 23% of the area at risk; P = .03). Significant positive correlations were observed between systolic aortic pressure and no reflow area, between systolic aortic pressure and infarcted area and between infarcted area and no reflow area during reperfusion. Modestly elevated blood pressure during reperfusion is associated with an increase in no reflow area and in infarct size in a clinically relevant porcine model of ischemia-reperfusion. © The Author(s) 2015.

Elevated serum uric acid affects myocardial reperfusion and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PubMed

Mandurino-Mirizzi, Alessandro; Crimi, Gabriele; Raineri, Claudia; Pica, Silvia; Ruffinazzi, Marta; Gianni, Umberto; Repetto, Alessandra; Ferlini, Marco; Marinoni, Barbara; Leonardi, Sergio; De Servi, Stefano; Oltrona Visconti, Luigi; De Ferrari, Gaetano M; Ferrario, Maurizio

2018-05-01

Elevated serum uric acid (eSUA) was associated with unfavorable outcome in patients with ST-segment elevation myocardial infarction (STEMI). However, the effect of eSUA on myocardial reperfusion injury and infarct size has been poorly investigated. Our aim was to correlate eSUA with infarct size, infarct size shrinkage, myocardial reperfusion grade and long-term mortality in STEMI patients undergoing primary percutaneous coronary intervention. We performed a post-hoc patients-level analysis of two randomized controlled trials, testing strategies for myocardial ischemia/reperfusion injury protection. Each patient underwent acute (3-5 days) and follow-up (4-6 months) cardiac magnetic resonance. Infarct size and infarct size shrinkage were outcomes of interest. We assessed T2-weighted edema, myocardial blush grade (MBG), corrected Thrombolysis in myocardial infarction Frame Count, ST-segment resolution and long-term all-cause mortality. A total of 101 (86.1% anterior) STEMI patients were included; eSUA was found in 16 (15.8%) patients. Infarct size was larger in eSUA compared with non-eSUA patients (42.3 ± 22 vs. 29.1 ± 15 ml, P = 0.008). After adjusting for covariates, infarct size was 10.3 ml (95% confidence interval 1.2-19.3 ml, P = 0.001) larger in eSUA. Among patients with anterior myocardial infarction the difference in delayed enhancement between groups was maintained (respectively, 42.3 ± 22.4 vs. 29.9 ± 15.4 ml, P = 0.015). Infarct size shrinkage was similar between the groups. Compared with non-eSUA, eSUA patients had larger T2-weighted edema (53.8 vs. 41.2 ml, P = 0.031) and less favorable MBG (MBG < 2: 44.4 vs. 13.6%, P = 0.045). Corrected Thrombolysis in myocardial infarction Frame Count and ST-segment resolution did not significantly differ between the groups. At a median follow-up of 7.3 years, all-cause mortality was higher in the eSUA group (18.8 vs. 2.4%, P = 0.028). eSUA may affect myocardial reperfusion in patients with STEMI undergoing percutaneous coronary intervention and is associated with larger infarct size and higher long-term mortality.

Hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation.

PubMed

Marsh, E B; Llinas, R H; Hillis, A E; Gottesman, R F

2013-06-01

Intracerebral hemorrhage (ICH) can occur in patients following acute ischaemic stroke in the form of hemorrhagic transformation, and results in significant long-term morbidity and mortality. Anticoagulation theoretically increases risk. We evaluated stroke patients with an indication for anticoagulation to determine the factors associated with hemorrhagic transformation. Three-hundred and forty-five patients with ICD-9 codes indicating: (i) acute ischaemic stroke; and (ii) an indication for anticoagulation were screened. One-hundred and twenty-three met inclusion criteria. Data were collected retrospectively. Neuroimaging was reviewed for infarct volume and evidence of ICH. Hemorrhages were classified as: hemorrhagic conversion (petechiae) versus intracerebral hematoma (a space occupying lesion); symptomatic versus asymptomatic. Using multivariable logistic regression, we determined the hypothesized factors associated with intracerebral bleeding. Age [odds ratio (OR) = 1.50 per 10-year increment, 95% confidence interval (CI) 1.07-2.08], infarct volume (OR = 1.10 per 10 ccs, 95% CI 1.06-1.18) and worsening category of renal impairment by estimated glomerular filtration rate (eGFR; OR = 1.95, 95% CI 1.04-3.66) were predictors of hemorrhagic transformation. Ninety- nine out of 123 patients were anticoagulated. Hemorrhage rates of patients on and off anticoagulation did not differ (25.3% vs. 20.8%; P = 0.79); however, all intracerebral hematomas (n = 7) and symptomatic bleeds (n = 8) occurred in the anticoagulated group. The risk of hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation is multifactorial, and most closely associated with an individual's age, infarct volume and eGFR. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Effect of supersaturated oxygen delivery on infarct size after percutaneous coronary intervention in acute myocardial infarction.

PubMed

Stone, Gregg W; Martin, Jack L; de Boer, Menko-Jan; Margheri, Massimo; Bramucci, Ezio; Blankenship, James C; Metzger, D Christopher; Gibbons, Raymond J; Lindsay, Barbara S; Weiner, Bonnie H; Lansky, Alexandra J; Krucoff, Mitchell W; Fahy, Martin; Boscardin, W John

2009-10-01

Myocardial salvage is often suboptimal after percutaneous coronary intervention in ST-segment elevation myocardial infarction. Posthoc subgroup analysis from a previous trial (AMIHOT I) suggested that intracoronary delivery of supersaturated oxygen (SSO(2)) may reduce infarct size in patients with large ST-segment elevation myocardial infarction treated early. A prospective, multicenter trial was performed in which 301 patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset were randomized to a 90-minute intracoronary SSO(2) infusion in the left anterior descending artery infarct territory (n=222) or control (n=79). The primary efficacy measure was infarct size in the intention-to-treat population (powered for superiority), and the primary safety measure was composite major adverse cardiovascular events at 30 days in the intention-to-treat and per-protocol populations (powered for noninferiority), with Bayesian hierarchical modeling used to allow partial pooling of evidence from AMIHOT I. Among 281 randomized patients with tc-99m-sestamibi single-photon emission computed tomography data in AMIHOT II, median (interquartile range) infarct size was 26.5% (8.5%, 44%) with control compared with 20% (6%, 37%) after SSO(2). The pooled adjusted infarct size was 25% (7%, 42%) with control compared with 18.5% (3.5%, 34.5%) after SSO(2) (P(Wilcoxon)=0.02; Bayesian posterior probability of superiority, 96.9%). The Bayesian pooled 30-day mean (+/-SE) rates of major adverse cardiovascular events were 5.0+/-1.4% for control and 5.9+/-1.4% for SSO(2) by intention-to-treat, and 5.1+/-1.5% for control and 4.7+/-1.5% for SSO(2) by per-protocol analysis (posterior probability of noninferiority, 99.5% and 99.9%, respectively). Among patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset, infusion of SSO(2) into the left anterior descending artery infarct territory results in a significant reduction in infarct size with noninferior rates of major adverse cardiovascular events at 30 days. Clinical Trial Registration- clinicaltrials.gov Identifier: NCT00175058.

Effect of provider volume on the accuracy of hospital report cards: a Monte Carlo study.

PubMed

Austin, Peter C; Reeves, Mathew J

2014-03-01

Hospital report cards, in which outcomes after the provision of medical or surgical care are compared across healthcare providers, are being published with increasing frequency. However, the accuracy of such comparisons is controversial, especially when case volumes are small. The objective was to determine the relationship between hospital case volume and the accuracy of hospital report cards. Monte Carlo simulations were used to examine the influence of hospital case volume on the accuracy of hospital report cards in a setting in which true hospital performance was known with certainty, and perfect risk-adjustment was feasible. The parameters used to generate the simulated data sets were obtained from empirical analyses of data on patients hospitalized with acute myocardial infarction in Ontario, Canada, in which the overall 30-day mortality rate was 11.1%. We found that provider volume had a strong effect on the accuracy of hospital report cards. However, provider volume had to be >300 before ≥70% of hospitals were correctly classified. Furthermore, hospital volume had to be >1000 before ≥80% of hospitals were correctly classified. Producers and users of hospital report cards need to be aware that, even when perfect risk adjustment is possible, the accuracy of hospital report cards is, at best, modest for small to medium-sized case loads (i.e., 100-300). Hospital report cards displayed high degrees of accuracy only when provider volumes exceeded the typical annual hospital case load for many cardiovascular conditions and procedures.

Creatine kinase radioimmunoassay and isoenzyme electrophoresis compared in the diagnosis of acute myocardial infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Homburger, H.A.; Jacob, G.L.

1980-07-01

We compared, in 116 patients, the relative usefulness of results of tests for creatine kinase B-isoenzymes, as measured by radioimmunoassay, and the MB isoenzyme, as measured by electrophoresis, in diagnosis of acute myocardial infarction. The radioimmunoassay was specific for isoenzymes of creatine kinase containing the B subunit. All patients with acute transmural infarcts had positive test results by both techniques, but concentrations of B-isoenzymes were more frequently above normal than were MB bands in the case of patients with acute subendocardial infarcts and in the case of all patients with acute myocardial infarcts from whom sera were collected more thanmore » 24 h after onset of chest pain. Concentrations of B-isoenzymes also were increased, even when MB bands were not electrophoretically detectable in specimens from several patients without documented acute myocardial infarcts. These abnormal results presumably were caused by increased concentrations of the BB isoenzyme in serum. Accordingly, an increased concentration of B-isoenzymes had less diagnostic specificity and predictive value for acute myocardial infarction than did a detectable MB band. Results of isoenzyme electrophoresis were more reliable for establishing this diagnosis, but the results of radioimmunoassay were more reliable for excluding it in patients with chest pain as the primary symptom.« less

Reduced creatine kinase release with statin use at the time of myocardial infarction.

PubMed

Bybee, Kevin A; Kopecky, Stephen L; Williams, Brent A; Murphy, Joseph G; Scott Wright, R

2004-09-01

Statin pre-treatment has been shown to reduce myocardial infarct size in animal models. We evaluated peak creatine kinase levels in humans based on concomitant or very early statin initiation following myocardial infarction. We identified 66 consecutive patients who received a statin within 24 h of admission to our coronary care unit for myocardial infarction. Each statin patient was matched with three patients who had not received statin therapy (n=198). Statin patients were subgrouped into those receiving statin therapy at the time of infarction (n=44) and those initiated on statin therapy within 24 h of infarction (n=22). Peak total creatine kinase concentrations were compared between groups. A linear regression model was developed to test for differences in peak creatine kinase after adjusting for differences between groups. Patients receiving statin therapy within 24 h of admission had significantly smaller median peak creatine kinase concentrations compared to those not receiving a statin (416 IU/l [258, 992] vs. 699 IU/l [339, 1728]; p=0.020). Subgroup analysis revealed that the lower peak creatine kinase concentrations within the statin group were a result of lower creatine kinase concentrations in those patients on a statin at the time of myocardial infarction (399 IU/l [255, 869] vs. 678 IU/l [276, 1870]; p<0.05). This difference retained statistical significance after adjustment for differences between groups. Statin therapy at the time of myocardial infarction is associated with lower peak creatine kinase concentrations. This suggests that statins may exhibit protective effects in the setting of myocardial ischemia and/or infarction in humans.

Morphometry of right ventricular hypertrophy induced by myocardial infarction in the rat.

PubMed Central

Anversa, P.; Beghi, C.; McDonald, S. L.; Levicky, V.; Kikkawa, Y.; Olivetti, G.

1984-01-01

The growth response of the right ventricle was studied in rats following ligation of the left coronary artery, which produced infarcts comprising approximately 40% of the left ventricle. A month after surgery the weight of the right ventricle was increased 30%, and this hypertrophic change was characterized by a 17% wall thickening, consistent with the 13% greater diameter of myocytes. Myocardial hypertrophy was accompanied by an inadequate growth of the microvasculature that supports tissue oxygenation. This was seen by relative decreases in capillary luminal volume density (-27%) and capillary luminal surface density (-21%) and by an increase in the average maximum distance from the capillary wall to the mitochondria of myocytes (19%). In contrast, measurements of the mean myocyte volume per nucleus showed a proportional enlargement of these cells (32%), from 16,300 cu mu in control animals to 21,500 cu mu in experimental rats. Quantitative analysis of the right coronary artery revealed a 33% increase in its luminal area, commensurate with the magnitude of ventricular hypertrophy. PMID:6236695

Improved hemodynamic parameters in middle cerebral artery infarction after decompressive craniectomy.

PubMed

Amorim, Robson Luis; de Andrade, Almir Ferreira; Gattás, Gabriel S; Paiva, Wellingson Silva; Menezes, Marcos; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

2014-05-01

Decompressive craniectomy (DC) reduces mortality and improves functional outcome in patients with malignant middle cerebral artery infarction. However, little is known regarding the impact of DC on cerebral hemodynamics. Therefore, our goal was to study the hemodynamic changes that may occur in patients with malignant middle cerebral artery infarction after DC and to assess their relationship with outcomes. Twenty-seven patients with malignant middle cerebral artery infarction who were treated with DC were studied. The perfusion CT hemodynamic parameters, mean transit time, cerebral blood flow, and cerebral blood volume were evaluated preoperatively and within the first 24 hours after DC. There was a global trend toward improved cerebral hemodynamics after DC. Preoperative and postoperative absolute mean transit times were associated with mortality at 6 months, and the ratio of post- and preoperative cerebral blood flow was significantly higher in patients with favorable outcomes than those with unfavorable outcomes. Patients who underwent surgery 48 hours after stroke, those with midline brain shift>10 mm, and those who were >55 years showed no significant improvement in any perfusion CT parameters. DC improves cerebral hemodynamics in patients with malignant middle cerebral artery infarction, and the level of improvement is related to outcome. However, some patients did not seem to experience any additional hemodynamic benefit, suggesting that perfusion CT may play a role as a prognostic tool in patients undergoing DC after ischemic stroke.

Evaluation of heart perfusion in patients with acute myocardial infarction using dynamic contrast-enhanced magnetic resonance imaging.

PubMed

Nielsen, Gitte; Fritz-Hansen, Thomas; Dirks, Christina G; Jensen, Gorm B; Larsson, Henrik B W

2004-09-01

To investigate the diagnostic ability of quantitative magnetic resonance imaging (MRI) heart perfusion in acute heart patients, a fast, multislice dynamic contrast-enhanced MRI sequence was applied to patients with acute myocardial infarction. Seven patients with acute transmural myocardial infarction were studied using a Turbo-fast low angle shot (FLASH) MRI sequence to monitor the first pass of an extravascular contrast agent (CA), gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). Quantitation of perfusion, expressed as Ki (mL/100 g/minute), in five slices, each having 60 sectors, provided an estimation of the severity and extent of the perfusion deficiency. Reperfusion was assessed both by noninvasive criteria and by coronary angiography (CAG). The Ki maps clearly delineated the infarction in all patients. Thrombolytic treatment was clearly beneficial in one case, but had no effect in the two other cases. Over the time-course of the study, normal perfusion values were not reestablished following thrombolytic treatment in all cases investigated. This study shows that quantitative MRI perfusion values can be obtained from acutely ill patients following acute myocardial infarction. The technique provides information on both the volume and severity of affected myocardial tissue, enabling the power of treatment regimes to be assessed objectively, and this approach should aid individual patient stratification and prognosis. Copyright 2004 Wiley-Liss, Inc.

Fibroblasts in myocardial infarction: a role in inflammation and repair

PubMed Central

Shinde, Arti V.; Frangogiannis, Nikolaos G.

2014-01-01

Fibroblasts do not only serve as matrix-producing reparative cells, but exhibit a wide range of functions in inflammatory and immune responses, angiogenesis and neoplasia. The adult mammalian myocardium contains abundant fibroblasts enmeshed within the interstitial and perivascular extracellular matrix. The current review manuscript discusses the dynamic phenotypic and functional alterations of cardiac fibroblasts following myocardial infarction. Extensive necrosis of cardiomyocytes in the infarcted heart triggers an intense inflammatory reaction. In the early stages of infarct healing, fibroblasts become pro-inflammatory cells, activating the inflammasome and producing cytokines, chemokines and proteases. Pro-inflammatory cytokines (such as Interleukin-1) delay myofibroblast transformation, until the wound is cleared from dead cells and matrix debris. Resolution of the inflammatory infiltrate is associated with fibroblast migration, proliferation, matrix protein synthesis and myofibroblast conversion. Growth factors and matricellular proteins play an important role in myofibroblast activation during the proliferative phase of healing. Formation of a mature cross-linked scar is associated with clearance of fibroblasts, as poorly-understood inhibitory signals restrain the fibrotic response. However, in the non-infarcted remodeling myocardium, local fibroblasts may remain activated in response to volume and pressure overload and may promote interstitial fibrosis. Considering their abundance, their crucial role in cardiac inflammation and repair, and their involvement in myocardial dysfunction and arrhythmogenesis, cardiac fibroblasts may be key therapeutic targets in cardiac remodeling. PMID:24321195

Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs.

PubMed

Andreka, Gyorgy; Vertesaljai, Marton; Szantho, Gergely; Font, Gusztav; Piroth, Zsolt; Fontos, Geza; Juhasz, Eszter D; Szekely, Laszlo; Szelid, Zsolt; Turner, Mark S; Ashrafian, Houman; Frenneaux, Michael P; Andreka, Peter

2007-06-01

Ischaemic preconditioning results in a reduction in ischaemic-reperfusion injury to the heart. This beneficial effect is seen both with direct local preconditioning of the myocardium and with remote preconditioning of easily accessible distant non-vital limb tissue. Ischaemic postconditioning with a comparable sequence of brief periods of local ischaemia, when applied immediately after the ischaemic insult, confers benefits similar to preconditioning. To test the hypothesis that limb ischaemia induces remote postconditioning and hence reduces experimental myocardial infarct size in a validated swine model of acute myocardial infarction. Acute myocardial infarction was induced in 24 pigs with 90 min balloon inflations of the left anterior descending coronary artery. Remote ischaemic postconditioning was induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after the balloon deflation. Infarct size was assessed by measuring 72 h creatinine kinase release, MRI scan and immunohistochemical analysis. Area under the curve of creatinine kinase release was significantly reduced in the postconditioning group compared with the control group with a 26% reduction in the infarct size (p<0.05). This was confirmed by MRI scanning and immunohistochemical analysis that revealed a 22% (p<0.05) and a 47.52% (p<0.01) relative reduction in the infarct size, respectively. Remote ischaemic postconditioning is a simple technique to reduce infarct size without the hazards and logistics of multiple coronary artery balloon inflations. This type of conditioning promises clear clinical potential.

Differential loss of natural killer cell activity in patients with acute myocardial infarction and stable angina pectoris.

PubMed

Yan, Wenwen; Zhou, Lin; Wen, Siwan; Duan, Qianglin; Huang, Feifei; Tang, Yu; Liu, Xiaohong; Chai, Yongyan; Wang, Lemin

2015-01-01

To evaluate the activity of natural killer cells through their inhibitory and activating receptors and quantity in peripheral blood mononuclear cells extracted from patients with acute myocardial infarction, stable angina pectoris and the controls. 100 patients with myocardial infarction, 100 with stable angina, and 20 healthy volunteers were recruited into the study. 20 randomly chosen people per group were examined for the whole human genome microarray analysis to detect the gene expressions of all 40 inhibitory and activating natural killer cell receptors. Flow cytometry analysis was applied to all 200 patients to measure the quantity of natural killer cells. In myocardial infarction group, the mRNA expressions of six inhibitory receptors KIR2DL2, KIR3DL3, CD94, NKG2A, KLRB1, KLRG1, and eight activating receptors KIR2DS3, KIR2DS5, NKp30, NTB-A, CRACC, CD2, CD7 and CD96 were significantly down-regulated (P<0.05) compared with both angina patients and the controls. There was no statistical difference in receptor expressions between angina patients and control group. The quantity of natural killer cells was significantly decreased in both infarction and angina patients compared with normal range (P<0.001). The significant mRNAs down-regulation of several receptors in myocardial infarction group and reduction in the quantity of natural killer cells in both myocardial infarction and angina patients showed a quantitative loss and dysfunction of natural killer cells in myocardial infarction patients.

Effects of Lacunar Infarctions on Cognitive Impairment in Patients with Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

PubMed Central

Choi, Jay Chol; Kang, Sa-Yoon; Kang, Ji-Hoon; Na, Hae Ri; Park, Ji-Kang

2011-01-01

Background and Purpose Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. Although previous studies have shown an association between lacunar infarction and cognitive impairment, the relationship between MRI parameters and cognition remains unclear. In this study we investigated the influence of MRI parameters on cognitive impairment in CADASIL. Methods We applied a prospective protocol to 40 patients. MRI analysis included the normalized volume of white-matter hyperintensities (nWMHs), number of lacunes, and number of cerebral microbleeds. Cognition was assessed with the aid of psychometric tests [Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognition (ADAS-cog), Trail-Making Test, and Stroop interference (Stroop IF)]. Results A multivariate regression analysis revealed that the total number of lacunes influenced the performance in the MMSE, ADAS-cog, and Stroop IF, while nWMHs had a strong univariate association with ADAS-cog and Stroop IF scores. However, this association disappeared in the multivariate analysis. Conclusions These findings demonstrate that the number of lacunes is the main predictive factor of cognitive impairment in CADASIL. PMID:22259617

The Highly Selective Caspase-1 Inhibitor VX-765 Provides Additive Protection Against Myocardial Infarction in Rat Hearts When Combined With a Platelet Inhibitor.

PubMed

Yang, Xi-Ming; Downey, James M; Cohen, Michael V; Housley, Nicole A; Alvarez, Diego F; Audia, Jonathon P

2017-11-01

Use of ischemic postconditioning and other related cardioprotective interventions to treat patients with acute myocardial infarction (AMI) has failed to improve outcomes in clinical trials. Because P2Y 12 inhibitors are themselves postconditioning mimetics, it has been postulated that the loading dose of platelet inhibitors routinely given to patients treated for AMI masks the anti-infarct effect of other intended cardioprotective interventions. To further improve outcomes of patients with AMI, an intervention must be able to provide additive protection in the presence of a P2Y 12 platelet inhibitor. Previous studies reported an anti-infarct effect using a peptide inhibitor of the pro-inflammatory caspase-1 in animal models of AMI. Herein we tested whether a pharmacologic caspase-1 inhibitor can further limit infarct size in open-chest, anesthetized rats treated with a P2Y 12 inhibitor. One hour occlusion of a coronary branch followed by 2 hours of reperfusion was used to simulate clinical AMI and reflow. One group of rats received an intravenous bolus of 16 mg/kg of the highly selective caspase-1 inhibitor VX-765 30 minutes prior to onset of ischemia. A second group received a 60 µg/kg intravenous bolus of the P2Y 12 inhibitor cangrelor 10 minutes prior to reperfusion followed by 6 µg/kg/min continuous infusion. A third group received treatment with both inhibitors as above. Control animals received no treatment. Infarct size was measured by tetrazolium stain and volume of muscle at risk by fluorescent microspheres. In untreated hearts, 73.7% ± 4.1% of the ischemic zone infarcted. Treatment with either cangrelor or VX-765 alone reduced infarct size to 43.8% ± 2.4% and 39.6% ± 3.6% of the ischemic zone, respectively. Combining cangrelor and VX-765 was highly protective, resulting in only 14.0% ± 2.9% infarction. The ability of VX-765 to provide protection beyond that of a platelet inhibitor alone positions it as an attractive candidate therapy to further improve outcomes in today's patients with AMI.

A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyanohara, Jun; Shirakawa, Hisashi, E-mail: shirakaw@pharm.kyoto-u.ac.jp; Sanpei, Kazuaki

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca{sup 2+} permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2more » days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.« less

Endogenous Agmatine Induced by Ischemic Preconditioning Regulates Ischemic Tolerance Following Cerebral Ischemia

PubMed Central

Kim, Jae Hwan; Kim, Jae Young; Jung, Jin Young; Lee, Yong Woo; Lee, Won Taek; Huh, Seung Kon

2017-01-01

Ischemic preconditioning (IP) is one of the most important endogenous mechanisms that protect the cells against ischemia-reperfusion (I/R) injury. However, the exact molecular mechanisms remain unclear. In this study, we showed that changes in the level of agmatine were correlated with ischemic tolerance. Changes in brain edema, infarct volume, level of agmatine, and expression of arginine decarboxylase (ADC) and nitric oxide synthases (NOS; inducible NOS [iNOS] and neural NOS [nNOS]) were analyzed during I/R injury with or without IP in the rat brain. After cerebral ischemia, brain edema and infarct volume were significantly reduced in the IP group. The level of agmatine was increased before and during ischemic injury and remained elevated in the early reperfusion phase in the IP group compared to the experimental control (EC) group. During IP, the level of plasma agmatine was increased in the early phase of IP, but that of liver agmatine was abruptly decreased. However, the level of agmatine was definitely increased in the ipsilateral and contralateral hemisphere of brain during the IP. IP also increased the expression of ADC—the enzyme responsible for the synthesis of endogenous agmatine—before, during, and after ischemic injury. In addition, ischemic injury increased endogenous ADC expression in the EC group. The expression of nNOS was reduced in the I/R injured brain in the IP group. These results suggest that endogenous increased agmatine may be a component of the ischemic tolerance response that is induced by IP. Agmatine may have a pivotal role in endogenous ischemic tolerance. PMID:29302205

Depletion of Cultivatable Gut Microbiota by Broad-Spectrum Antibiotic Pretreatment Worsens Outcome After Murine Stroke

PubMed Central

Winek, Katarzyna; Engel, Odilo; Koduah, Priscilla; Heimesaat, Markus M.; Fischer, André; Bereswill, Stefan; Dames, Claudia; Kershaw, Olivia; Gruber, Achim D.; Curato, Caterina; Oyama, Naoki; Meisel, Christian; Meisel, Andreas

2016-01-01

Background and Purpose— Antibiotics disturbing microbiota are often used in treatment of poststroke infections. A bidirectional brain–gut microbiota axis was recently suggested as a modulator of nervous system diseases. We hypothesized that gut microbiota may be an important player in the course of stroke. Methods— We investigated the outcome of focal cerebral ischemia in C57BL/6J mice after an 8-week decontamination with quintuple broad-spectrum antibiotic cocktail. These microbiota-depleted animals were subjected to 60 minutes middle cerebral artery occlusion or sham operation. Infarct volume was measured using magnetic resonance imaging, and mice were monitored clinically throughout the whole experiment. At the end point, tissues were preserved for further analysis, comprising histology and immunologic investigations using flow cytometry. Results— We found significantly decreased survival in the middle cerebral artery occlusion microbiota-depleted mice when the antibiotic cocktail was stopped 3 days before surgery (compared with middle cerebral artery occlusion specific pathogen-free and sham-operated microbiota-depleted mice). Moreover, all microbiota-depleted animals in which antibiotic treatment was terminated developed severe acute colitis. This phenotype was rescued by continuous antibiotic treatment or colonization with specific pathogen-free microbiota before surgery. Further, infarct volumes on day one did not differ between any of the experimental groups. Conclusions— Conventional microbiota ensures intestinal protection in the mouse model of experimental stroke and prevents development of acute and severe colitis in microbiota-depleted mice not given antibiotic protection after cerebral ischemia. Our experiments raise the clinically important question as to whether microbial colonization or specific microbiota are crucial for stroke outcome. PMID:27056982

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Qiang; Department of Neurology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011; Zhang, Ting

Highlights: • Rapamycin enhances mitophagy via increasing p62 translocation to the mitochondria. • Rapamycin attenuates brain ischemic damage and improves mitochondrial function. • The protection of rapamycin to mitochondrial is linked to enhanced mitophagy. - Abstract: Rapamycin has been demonstrated to exhibit neuroprotective functions via the activation of autophagy in a cerebral ischemia model. However, the involvement of mitophagy in this process and its contribution to the protection of mitochondrial function remains unknown. The present study explored the characteristics of mitophagy after cerebral ischemia and the effect of rapamycin on mitochondrial function. Male Sprague–Dawley rats underwent transient middle cerebral arterymore » occlusion (tMCAO). Neurological deficits scores; infarct volumes; mitophagy morphology; and the levels of malondialdehyde (MDA), adenosine triphosphate (ATP) and mitochondrial membrane potentials (Δψm) were examined. The expression of LC3, Beclin-1 and p62 in the mitochondrial fraction combined with transmission electronic microscopy were used to explore mitophagic activity after ischemia. We also blocked autophagosome formation using 3-methyladenine (3-MA) to check the linkage between the mitochondrial protective effect of rapamycin and enhanced mitophagy. We observed that rapamycin significantly enhanced mitophagy, as evidenced by the increase in LC3-II and Beclin-1 expression in the mitochondria and p62 translocation to the mitochondria. Rapamycin reduced infarct volume, improved neurological outcomes and inhibited mitochondrial dysfunction compared with the control animals (p < 0.05). However, these protective effects were reversed by 3-methyladenine treatment after rapamycin. The present study indicates that rapamycin treatment attenuates mitochondrial dysfunction following cerebral ischemia, which is linked to enhanced mitophagy.« less

Relationship Between Visceral Infarction and Ischemic Stroke Subtype.

PubMed

Finn, Caitlin; Hung, Peter; Patel, Praneil; Gupta, Ajay; Kamel, Hooman

2018-03-01

Most cryptogenic strokes are thought to have an embolic source. We sought to determine whether cryptogenic strokes are associated with visceral infarcts, which are usually embolic. Among patients prospectively enrolled in CAESAR (Cornell Acute Stroke Academic Registry), we selected those with a contrast-enhanced abdominal computed tomographic scan within 1 year of admission. Our exposure variable was adjudicated stroke subtype per the Trial of ORG 10172 in Acute Stroke Treatment classification. Our outcome was renal or splenic infarction as assessed by a single radiologist blinded to stroke subtype. We used Fisher exact test and multiple logistic regression to compare the prevalence of visceral infarcts among cardioembolic strokes, strokes of undetermined etiology, and noncardioembolic strokes (large- or small-vessel strokes). Among 227 patients with ischemic stroke and a contrast-enhanced abdominal computed tomographic scan, 59 had a visceral infarct (35 renal and 27 splenic). The prevalence of visceral infarction was significantly different among cardioembolic strokes (34.2%; 95% confidence interval [CI], 23.7%-44.6%), strokes of undetermined etiology (23.9%; 95% CI, 15.0%-32.8%), and strokes from large-artery atherosclerosis or small-vessel occlusion (12.5%; 95% CI, 1.8%-23.2%; P =0.03). In multiple logistic regression models adjusted for demographics and vascular comorbidities, we found significant associations with visceral infarction for both cardioembolic stroke (odds ratio, 3.5; 95% CI, 1.2-9.9) and stroke of undetermined source (odds ratio, 3.3; 95% CI, 1.1-10.5) as compared with noncardioembolic stroke. The prevalence of visceral infarction differed significantly across ischemic stroke subtypes. Cardioembolic and cryptogenic strokes were associated with a higher prevalence of visceral infarcts than noncardioembolic strokes. © 2018 American Heart Association, Inc.

Effect of intravascular irradiation of He-Ne laser on cerebral infarction: Hemorrheology and apoptosis

NASA Astrophysics Data System (ADS)

Zhu, Jian; Liang, Min-yi; Cao, Hao-cai; Li, Xiao-Yuan; Li, Shao-ming; Li, Shun-hao; Li, Wen-qi; Zhang, Jin-hong; Liu, Lei; Lai, Jian-hong

2005-07-01

Objective: To explore the efficacy of He-Ne laser intravascular irradiation on infarction and hemorrheology. To observe the effects of intravascular low level He-Ne laser irradiation (ILLLI) of blood on cell proliferation, apoptosis and chromosome in lymphocyte from cerebral infarction Methods: Seventy cases with cerebral infarction were randomly divided into groups control group (35 cases) treated only with common drugs and therapeutic group (35 cases) treated besides common drugs also by He-Ne laser intravascular irradiation. Their hemorrheology index and treatment results were observed and compared. The blood lymphocytes of cerebral infarction were cultured before and after treatment. After that, the mitosis index (MI), cell kinetics index (CKI), sister-chromatid exchanges (SCE) frequencies and apoptosis were determined. Results The therapeutic group was better than the control one. The effective rate in the therapeutic group was 88.6%, in the control one was 65.7%. The viscosity and fibrinogen, etc were better than that in the control group with significant difference (P<0.01). The lymphocyte proliferation index was significantly two increased than the control one (P>0.05) in cerebral infarction patients after treatment; The CKI of lymphocytes had no obvious difference among groups (P>0.05) SCE frequencies of lymphocytes had no statistic significance between control group and ILLLI on (P>0.05). It showed the apoptosis rate of lymphocytes in cerebral infarction patients after ILLLI treatment increased significantly compared with the control group, (P<0.001). There was a significant difference of apoptosis rate of lymphocytes in cerebral infarction patients than the control (P<0.001). Conclusions: During the He-Ne laser intravascular irradiation of the cerebral infarction, the low level He-Ne by ILLLI can increase the proliferation of lymphocytes, and can induce lymphocytes to apoptosis, but has no mutagenicity of cells.

5'-adenosine monophosphate-induced hypothermia attenuates brain ischemia/reperfusion injury in a rat model by inhibiting the inflammatory response.

PubMed

Miao, Yi-Feng; Wu, Hui; Yang, Shao-Feng; Dai, Jiong; Qiu, Yong-Ming; Tao, Zhen-Yi; Zhang, Xiao-Hua

2015-01-01

Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5'-adenosine monophosphate (5'-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5'-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5'-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.

Acute lesions that impair affective empathy

PubMed Central

Oishi, Kenichi; Hsu, John; Lindquist, Martin; Gottesman, Rebecca F.; Jarso, Samson; Crainiceanu, Ciprian; Mori, Susumu

2013-01-01

Functional imaging studies of healthy participants and previous lesion studies have provided evidence that empathy involves dissociable cognitive functions that rely on at least partially distinct neural networks that can be individually impaired by brain damage. These studies converge in support of the proposal that affective empathy—making inferences about how another person feels—engages at least the following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, anterior cingulate cortex, temporal pole, amygdala and temporoparietal junction. We hypothesized that right-sided lesions to any one of these structures, except temporoparietal junction, would cause impaired affective empathy (whereas bilateral damage to temporoparietal junction would be required to disrupt empathy). We studied 27 patients with acute right hemisphere ischaemic stroke and 24 neurologically intact inpatients on a test of affective empathy. Acute impairment of affective empathy was associated with infarcts in the hypothesized network, particularly temporal pole and anterior insula. All patients with impaired affective empathy were also impaired in comprehension of affective prosody, but many patients with impairments in prosodic comprehension had spared affective empathy. Patients with impaired affective empathy were older, but showed no difference in performance on tests of hemispatial neglect, volume of infarct or sex distribution compared with patients with intact affective empathy. PMID:23824490

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

PubMed Central

Hu, Heng; Doll, Danielle N.; Sun, Jiahong; Lewis, Sara E.; Wimsatt, Jeffrey H.; Kessler, Matthew J.; Simpkins, James W.; Ren, Xuefang

2016-01-01

Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for stroke severity in experimental stroke animal models and may have translational significance for clinical stroke patients - targeting endothelial mitochondria may be a clinically useful approach for stroke therapy. PMID:26816660

Culprit versus multivessel coronary intervention in ST-segment elevation myocardial infarction: a meta-analysis of randomized trials.

PubMed

Vaidya, Satyanarayana R; Qamar, Arman; Arora, Sameer; Devarapally, Santhosh R; Kondur, Ashok; Kaul, Prashant

2018-03-01

The 2015 American College of Cardiology/American Heart Association update on primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) recommended PCI of the non-infarct-related artery at the time of primary PCI (class IIb recommendation). Despite evidence supporting complete revascularization in STEMI, its benefit on mortality rates is uncertain. We searched all available databases for randomized controlled trials comparing complete multivessel percutaneous coronary intervention (CMV PCI) with infarct-artery-only revascularization in patients with STEMI. Summary risk ratios and 95% confidence intervals (CIs) were calculated for both the efficacy and safety outcomes. Nine randomized controlled trials fulfilled the inclusion criteria, yielding 2991 patients. Follow-up periods ranged from 6 to 36 months. Compared with infarct-related artery-only PCI, CMV PCI was associated with significantly lower rates of major adverse cardiac events [relative risk (RR)=0.54, 95% CI=0.41-0.71; P<0.00001], cardiovascular mortality (RR=0.48, 95% CI=0.28-0.80; P=0.005), and repeat revascularization (RR=0.38, 95% CI=0.30-0.47; P<0.00001). Although, contrast-induced nephropathy and major bleed rates were comparable between both groups, CMV PCI failed to show any reduction in all-cause mortality (RR=0.75, 95% CI=0.53-1.07; P=0.11) and nonfatal myocardial infarction (RR=0.69, 95% CI=0.43-1.10; P=0.12). Our results suggest that in patients with STEMI and multivessel disease, complete revascularization is safe, and is associated with reduced risks of major adverse cardiac events and cardiac death along with a reduced need for repeat revascularization. However, it showed no beneficial effect on all-cause mortality and nonfatal myocardial infarction.

Twelve-month clinical outcomes of acute non-ST versus ST-segment elevation myocardial infarction patients with reduced preprocedural thrombolysis in myocardial infarction flow undergoing percutaneous coronary intervention.

PubMed

Baek, Ju Yeol; Kang, Tae Soo; Rha, Seung-Woon; Choi, Byoung Geol; Park, Sang Ho; Jeong, Myung Ho

2018-04-27

Reduced preprocedural thrombolysis in myocardial infarction (TIMI) flow in patients with ST-segment elevation myocardial infarction (STEMI) is known to be associated with increased mortality. However, clinical implications of reduced preprocedural TIMI flow in patients with non-ST-segment elevation myocardial infarction (NSTEMI) have not been fully elucidated as yet. The aim of the present study was to compare the clinical influence of reduced preprocedural TIMI flows between patients with STEMI and NSTEMI undergoing percutaneous coronary intervention (PCI). From the Korea Acute Myocardial Infarction Registry, a total of 7336 AMI patients with angiographically confirmed reduced preprocedural TIMI flow (TIMI 0/1) during PCI were selected and divided into STEMI (n=4852) and NSTEMI (n=2484) groups. The 12-month composite of total death, nonfatal myocardial infarction, coronary artery bypass graft, and repeated PCI was compared between the two groups. After adjustment of baseline confounders by propensity score stratification, the NSTEMI group had lower incidences of major adverse cardiac events than the STEMI group (7.15 vs. 11.19%; hazard ratio: 0.63; 95% confidence interval: 0.47-0.84; P=0.001) at 12 months, which was largely attributable to the lower incidences of total deaths (2.43 vs. 3.99%; P=0.04) and repeated PCI (3.81 vs. 6.41%; P=0.01). Among AMI patients with TIMI 0/1, patients with NSTEMI had better outcomes compared with those of patients with STEMI on the basis of the incidences of 12-month outcomes. This could be attributable to lower total death and repeated revascularization in patients with NSTEMI.

Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction

PubMed Central

Beaumont, Eric; Southerland, Elizabeth M.; Hardwick, Jean C.; Wright, Gary L.; Ryan, Shannon; Li, Ying; KenKnight, Bruce H.; Armour, J. Andrew

2015-01-01

This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. PMID:26276818

Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction.

PubMed

Beaumont, Eric; Southerland, Elizabeth M; Hardwick, Jean C; Wright, Gary L; Ryan, Shannon; Li, Ying; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

2015-10-01

This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. Copyright © 2015 the American Physiological Society.

Study design for the "effect of METOprolol in CARDioproteCtioN during an acute myocardial InfarCtion" (METOCARD-CNIC): a randomized, controlled parallel-group, observer-blinded clinical trial of early pre-reperfusion metoprolol administration in ST-segment elevation myocardial infarction.

PubMed

Ibanez, Borja; Fuster, Valentin; Macaya, Carlos; Sánchez-Brunete, Vicente; Pizarro, Gonzalo; López-Romero, Pedro; Mateos, Alonso; Jiménez-Borreguero, Jesús; Fernández-Ortiz, Antonio; Sanz, Ginés; Fernández-Friera, Leticia; Corral, Ervigio; Barreiro, Maria-Victoria; Ruiz-Mateos, Borja; Goicolea, Javier; Hernández-Antolín, Rosana; Acebal, Carlos; García-Rubira, Juan Carlos; Albarrán, Agustín; Zamorano, José Luis; Casado, Isabel; Valenciano, Juan; Fernández-Vázquez, Felipe; de la Torre, José María; Pérez de Prado, Armando; Iglesias-Vázquez, José Antonio; Martínez-Tenorio, Pedro; Iñiguez, Andrés

2012-10-01

Infarct size predicts post-infarction mortality. Oral β-blockade within 24 hours of a ST-segment elevation acute myocardial infarction (STEMI) is a class-IA indication, however early intravenous (IV) β-blockers initiation is not encouraged. In recent magnetic resonance imaging (MRI)-based experimental studies, the β(1)-blocker metoprolol has been shown to reduce infarct size only when administered before coronary reperfusion. To date, there is not a single trial comparing the pre- vs. post-reperfusion β-blocker initiation in STEMI. The METOCARD-CNIC trial is testing whether the early initiation of IV metoprolol before primary percutaneous coronary intervention (pPCI) could reduce infarct size and improve outcomes when compared to oral post-pPCI metoprolol initiation. The METOCARD-CNIC trial is a randomized parallel-group single-blind (to outcome evaluators) clinical effectiveness trial conducted in 5 Counties across Spain that will enroll 220 participants. Eligible are 18- to 80-year-old patients with anterior STEMI revascularized by pPCI ≤6 hours from symptom onset. Exclusion criteria are Killip-class ≥III, atrioventricular block or active treatment with β-blockers/bronchodilators. Primary end point is infarct size evaluated by MRI 5 to 7 days post-STEMI. Prespecified major secondary end points are salvage-index, left ventricular ejection fraction recovery (day 5-7 to 6 months), the composite of (death/malignant ventricular arrhythmias/reinfarction/admission due to heart failure), and myocardial perfusion. The METOCARD-CNIC trial is testing the hypothesis that the early initiation of IV metoprolol pre-reperfusion reduces infarct size in comparison to initiation of oral metoprolol post-reperfusion. Given the implications of infarct size reduction in STEMI, if positive, this trial might evidence that a refined use of an approved inexpensive drug can improve outcomes of patients with STEMI. Copyright © 2012 Mosby, Inc. All rights reserved.

Hammersmith cardiology workshop series. Volume 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maseri, A.; Sobel, B.E.; Chierchia, S.

1987-01-01

This book contains over 40 selections. Some of the titles are: Nuclear Cardiology: A Decade of Clinical Use for the Detection of Coronary Artery Disease; Characterization of Ischemic Myocardium with Positron Emission Tomography; Postmortem Findings in Acute Myocardial Infarction; Mechanisms of Coronary Obstructions; and Correlation Between Exercise Stress Testing and Coronary Angiography.

Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs

PubMed Central

Andreka, Gyorgy; Vertesaljai, Marton; Szantho, Gergely; Font, Gusztav; Piroth, Zsolt; Fontos, Geza; Juhasz, Eszter D; Szekely, Laszlo; Szelid, Zsolt; Turner, Mark S; Ashrafian, Houman; Frenneaux, Michael P

2007-01-01

Background Ischaemic preconditioning results in a reduction in ischaemic‐reperfusion injury to the heart. This beneficial effect is seen both with direct local preconditioning of the myocardium and with remote preconditioning of easily accessible distant non‐vital limb tissue. Ischaemic postconditioning with a comparable sequence of brief periods of local ischaemia, when applied immediately after the ischaemic insult, confers benefits similar to preconditioning. Objective To test the hypothesis that limb ischaemia induces remote postconditioning and hence reduces experimental myocardial infarct size in a validated swine model of acute myocardial infarction. Methods Acute myocardial infarction was induced in 24 pigs with 90 min balloon inflations of the left anterior descending coronary artery. Remote ischaemic postconditioning was induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after the balloon deflation. Infarct size was assessed by measuring 72 h creatinine kinase release, MRI scan and immunohistochemical analysis. Results Area under the curve of creatinine kinase release was significantly reduced in the postconditioning group compared with the control group with a 26% reduction in the infarct size (p<0.05). This was confirmed by MRI scanning and immunohistochemical analysis that revealed a 22% (p<0.05) and a 47.52% (p<0.01) relative reduction in the infarct size, respectively. Conclusion Remote ischaemic postconditioning is a simple technique to reduce infarct size without the hazards and logistics of multiple coronary artery balloon inflations. This type of conditioning promises clear clinical potential. PMID:17449499

Demonstration of elevation and localization of Rho-kinase activity in the brain of a rat model of cerebral infarction.

PubMed

Yano, Kazuo; Kawasaki, Koh; Hattori, Tsuyoshi; Tawara, Shunsuke; Toshima, Yoshinori; Ikegaki, Ichiro; Sasaki, Yasuo; Satoh, Shin-ichi; Asano, Toshio; Seto, Minoru

2008-10-10

Evidence that Rho-kinase is involved in cerebral infarction has accumulated. However, it is uncertain whether Rho-kinase is activated in the brain parenchyma in cerebral infarction. To answer this question, we measured Rho-kinase activity in the brain in a rat cerebral infarction model. Sodium laurate was injected into the left internal carotid artery, inducing cerebral infarction in the ipsilateral hemisphere. At 6 h after injection, increase of activating transcription factor 3 (ATF3) and c-Fos was found in the ipsilateral hemisphere, suggesting that neuronal damage occurs. At 0.5, 3, and 6 h after injection of laurate, Rho-kinase activity in extracts of the cerebral hemispheres was measured by an ELISA method. Rho-kinase activity in extracts of the ipsilateral hemisphere was significantly increased compared with that in extracts of the contralateral hemisphere at 3 and 6 h but not 0.5 h after injection of laurate. Next, localization of Rho-kinase activity was evaluated by immunohistochemical analysis in sections of cortex and hippocampus including infarct area 6 h after injection of laurate. Staining for phosphorylation of myosin-binding subunit (phospho-MBS) and myosin light chain (phospho-MLC), substrates of Rho-kinase, was elevated in neuron and blood vessel, respectively, in ipsilateral cerebral sections, compared with those in contralateral cerebral sections. These findings indicate that Rho-kinase is activated in neuronal and vascular cells in a rat cerebral infarction model, and suggest that Rho-kinase could be an important target in the treatment of cerebral infarction.

Computed Tomographic Perfusion Predicts Poor Outcomes in a Randomized Trial of Endovascular Therapy.

PubMed

Wannamaker, Robert; Guinand, Taurian; Menon, Bijoy K; Demchuk, Andrew; Goyal, Mayank; Frei, Donald; Bharatha, Aditya; Jovin, Tudor G; Shankar, Jai; Krings, Timo; Baxter, Blaise; Holmstedt, Christine; Swartz, Richard; Dowlatshahi, Dar; Chan, Richard; Tampieri, Donatella; Choe, Hana; Burns, Paul; Gentile, Nina; Rempel, Jeremy; Shuaib, Ashfaq; Buck, Brian; Bivard, Andrew; Hill, Michael; Butcher, Kenneth

2018-06-01

In the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), patients with large vessel occlusions and small infarct cores identified with computed tomography (CT)/CT angiography were randomized to endovascular therapy or standard of care. CT perfusion (CTP) was obtained in some cases but was not used to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. All CTP data acquired in ESCAPE patients were analyzed centrally using a semiautomated perfusion threshold-based approach. A penumbral pattern was defined as an infarct core <70 mL, penumbral volume >15 mL, and a total hypoperfused volume:core volume ratio of >1.8. The primary outcome was good functional outcome at 90 days (modified Rankin Scale score, 0-2). CTP was acquired in 138 of 316 ESCAPE patients. Penumbral patterns were present in 116 of 128 (90.6%) of patients with interpretable CTP data. The rate of good functional outcome in penumbral pattern patients (53 of 114; 46%) was higher than that in nonpenumbral patients (2 of 12; 17%; P =0.041). In penumbral patients, endovascular therapy increased the likelihood of a good clinical outcome (34 of 58; 57%) compared with those in the control group (19 of 58; 33%; odds ratio, 2.68; 95% confidence interval, 1.25-5.76; P =0.011). Only 3 of 12 nonpenumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Nonpenumbral patients were much less likely to achieve good outcomes. © 2018 American Heart Association, Inc.

[Anomalous origin of the left coronary artery from the pulmonary trunk with myocardial infarction and severe left ventricular dysfunction in infancy--assessment of myocardial damage using SPECT studies with 201TlCl and 123I-BMIPP].

PubMed

Miyamoto, T; Horigome, H; Sato, H; Yamada, M; Inai, K; Takeda, T; Ishikawa, N; Hoshino, H; Itai, Y

1996-02-01

A 4-month-old male infant with Bland-White-Garland (BWG) syndrome complicated myocardial infarction was reported. Signs included tachypnea, coughing, and failure to thrive. However, there was no sign of myocardial infarction. A chest radiograph revealed cardiomegaly (CTR = 65%) and electrocardiogram showed abnormal Q waves in I, aVL, V6 leads. Cardiac catheterization and angiography revealed marked dilatation of left ventricle (end-diastolic volume = 384 ml/m2) and extremely depressed ejection fraction (16%), confirming the diagnosis of BWG syndrome. A 201TlCl-myocardial SPECT demonstrated apical defect and hypoperfusion in the anterolateral, inferoposterior walls, whereas 123I-beta-methyl-p-iodophenylpentadecanoic-acid (123I-BMIPP) SPECT showed a wider defect area. SPECT studies with 201TlCl and 123I-BMIPP, are useful to assess myocardial viability more accurately in BWG syndrome.

BID Mediates Oxygen-Glucose Deprivation-Induced Neuronal Injury in Organotypic Hippocampal Slice Cultures and Modulates Tissue Inflammation in a Transient Focal Cerebral Ischemia Model without Changing Lesion Volume

PubMed Central

Martin, Nellie Anne; Bonner, Helena; Elkjær, Maria Louise; D’Orsi, Beatrice; Chen, Gang; König, Hans Georg; Svensson, Martina; Deierborg, Tomas; Pfeiffer, Shona; Prehn, Jochen H.; Lambertsen, Kate Lykke

2016-01-01

The BH3 interacting-domain death agonist (BID) is a pro-apoptotic protein involved in death receptor-induced and mitochondria-mediated apoptosis. Recently, it has also been suggested that BID is involved in the regulation of inflammatory responses in the central nervous system. We found that BID deficiency protected organotypic hippocampal slice cultures in vitro from neuronal injury induced by oxygen-glucose deprivation. In vivo, BID-knockout (KO) mice and wild type (WT) mice were subjected to 60 min of transient middle cerebral artery occlusion (tMCAO) to induce focal cerebral ischemia, and allowed to recover for 24 h. Infarct volumes and functional outcome were assessed and the inflammatory response was evaluated using immunofluorescence, Western blotting, quantitative PCR (qPCR) and Mesoscale multiplex analysis. We observed no difference in the infarct volume or neurological outcome between BID-KO and WT mice. The inflammatory response was reduced by BID deficiency as indicated by a change in microglial/leukocyte response. In conclusion, our data suggest that BID deficiency is neuroprotective in an in vitro model and modulates the inflammatory response to focal cerebral ischemia in vivo. However, this is not translated into a robust neuroprotection in vivo. PMID:26869884

The 1999 Ji-Ji (Taiwan) earthquake as a trigger for acute myocardial infarction.

PubMed

Tsai, Ching-Hong; Lung, For-Wey; Wang, Shing-Yaw

2004-01-01

The authors evaluated the effect of stress due to the Ji-Ji, Taiwan, earthquake, which occurred at 1:47 a.m. on September 21, 1999, on the onset of acute myocardial infarction in six counties near the earthquake epicenter. The rate of hospitalization due to acute myocardial infarction increased during the 6 weeks after the earthquake, and a significantly higher number of patients were hospitalized with acute myocardial infarction during that period, compared with the same 6-week period in the previous year (99 and 65 patients, respectively). The findings suggest that extreme emotional stress due to the natural disaster, superimposed on the stress of awakening, increased the incidence of acute myocardial infarction in this population.

Neuroanatomic correlates of stroke-related myocardial injury.

PubMed

Ay, H; Koroshetz, W J; Benner, T; Vangel, M G; Melinosky, C; Arsava, E M; Ayata, C; Zhu, M; Schwamm, L H; Sorensen, A G

2006-05-09

Myocardial injury can occur after ischemic stroke in the absence of primary cardiac causes. The neuroanatomic basis of stroke-related myocardial injury is not well understood. To identify regions of brain infarction associated with myocardial injury using a method free of the bias of an a priori hypothesis as to any specific location. Of 738 consecutive patients with acute ischemic stroke, the authors identified 50 patients in whom serum cardiac troponin T (cTnT) elevation occurred in the absence of any apparent cause within 3 days of symptom onset. Fifty randomly selected, age- and sex-matched patients with ischemic stroke without cTnT elevation served as controls. Diffusion-weighted images with outlines of infarction were co-registered to a template, averaged, and then subtracted to find voxels that differed between the two groups. Voxel-wise p values were determined using a nonparametric permutation test to identify specific regions of infarction that were associated with cTnT elevation. The study groups were well balanced with respect to stroke risk factors, history of coronary artery disease, infarction volume, and frequency of right and left middle cerebral artery territory involvement. Brain regions that were a priori associated with cTnT elevation included the right posterior, superior, and medial insula and the right inferior parietal lobule. Among patients with right middle cerebral artery infarction, the insular cluster was involved in 88% of patients with and 33% without cTnT elevation (odds ratio: 15.00; 95% CI: 2.65 to 84.79). Infarctions in specific brain regions including the right insula are associated with elevated serum cardiac troponin T level indicative of myocardial injury.

Malignant infarction of the middle cerebral artery in a porcine model. A pilot study.

PubMed

Arikan, Fuat; Martínez-Valverde, Tamara; Sánchez-Guerrero, Ángela; Campos, Mireia; Esteves, Marielle; Gandara, Dario; Torné, Ramon; Castro, Lidia; Dalmau, Antoni; Tibau, Joan; Sahuquillo, Juan

2017-01-01

Interspecies variability and poor clinical translation from rodent studies indicate that large gyrencephalic animal stroke models are urgently needed. We present a proof-of-principle study describing an alternative animal model of malignant infarction of the middle cerebral artery (MCA) in the common pig and illustrate some of its potential applications. We report on metabolic patterns, ionic profile, brain partial pressure of oxygen (PtiO2), expression of sulfonylurea receptor 1 (SUR1), and the transient receptor potential melastatin 4 (TRPM4). A 5-hour ischemic infarct of the MCA territory was performed in 5 2.5-to-3-month-old female hybrid pigs (Large White x Landrace) using a frontotemporal approach. The core and penumbra areas were intraoperatively monitored to determine the metabolic and ionic profiles. To determine the infarct volume, 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry analysis was performed to determine SUR1 and TRPM4 expression. PtiO2 monitoring showed an abrupt reduction in values close to 0 mmHg after MCA occlusion in the core area. Hourly cerebral microdialysis showed that the infarcted tissue was characterized by reduced concentrations of glucose (0.03 mM) and pyruvate (0.003 mM) and increases in lactate levels (8.87mM), lactate-pyruvate ratio (4202), glycerol levels (588 μM), and potassium concentration (27.9 mmol/L). Immunohistochemical analysis showed increased expression of SUR1-TRPM4 channels. The aim of the present proof-of-principle study was to document the feasibility of a large animal model of malignant MCA infarction by performing transcranial occlusion of the MCA in the common pig, as an alternative to lisencephalic animals. This model may be useful for detailed studies of cerebral ischemia mechanisms and the development of neuroprotective strategies.

Clinical implications of increased use of MRI in TIA.

PubMed

Kvistad, C E; Thomassen, L; Waje-Andreassen, U; Moen, G; Logallo, N; Naess, H

2013-07-01

Transient ischemic attack has been redefined as a tissue-based diagnosis and MRI recommended as the preferred imaging modality. We aimed to investigate whether an increased use of MRI leads to a decrease in the proportion of TIA as compared to cerebral infarction. We also sought to see whether DWI-positive patients with transient ischemic symptoms <24 h differ from DWI-negative TIA patients in terms of performed diagnostic investigations and clinical characteristics. Patients admitted with cerebral infarction or TIA in the period 2006-2011 were prospectively registered. The use of MRI in patients with transient ischemic symptoms <24 h and proportion of TIA were annually recorded. DWI-positive and DWI-negative patients with transient ischemic symptoms <24 h were compared in univariate analyses regarding baseline data, diagnostic investigations, and etiology. Multivariate analyses were performed to identify predictors of DWI lesions. The use of MRI increased from 65.0% in 2006-2008 to 89.0% in 2009-2011 (P < 0.001). The proportion of TIA as compared to cerebral infarction decreased from 12.2% in 2006-2008 to 8.3% in 2009-2011 (P = 0.002). DWI-positive patients were more often examined with 24-h Holter monitoring (P < 0.001) and echocardiography (P < 0.001). Lower age (P < 0.001) and prior myocardial infarction (P < 0.029) were independently associated with DWI lesions in patients with transient ischemic symptoms <24 h. An increased use of MRI and a tissue-based TIA definition resulted in a decrease in the proportion of TIA at discharge as compared to cerebral infarction. DWI-positive patients had a more extensive cardiac work-up and were associated with lower age and prior myocardial infarction. © 2012 John Wiley & Sons A/S.

Shengui Sansheng San extraction is an angiogenic switch via regulations of AKT/mTOR, ERK1/2 and Notch1 signal pathways after ischemic stroke.

PubMed

Liu, Bowen; Luo, Cheng; Zheng, Zhaoguang; Xia, Zhenyan; Zhang, Qian; Ke, Chienchih; Liu, Renshyan; Zhao, Yonghua

2018-05-15

As a traditional Chinese herbal formula, Shengui Sansheng San (SSS) has been employed for stroke treatment more than 300 years. We hypothesize that SSS extraction is an angiogenic switch in penumbra post-stroke, and corresponding mechanisms are investigated. In present study, rats were subjected to permanent middle cerebral artery occlusion model (MCAo) and were treated with low, middle and high doses of SSS extraction. We assessed neurological function and survival rate, and measured infarct volume by 2,3,5-triphenyltetrazolium chloride staining on day 7 after ischemia. von Willebrand factor (vWF), stromal cell-derived factor-1 alpha (SDF-1α) /chemokine (C-X-C motif) receptor 4 (CXCR4) axis, vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) as well as protein kinase B (AKT)/mammalian target of rapamycin (mTOR) /hypoxia-inducible factor-1 alpha (HIF-1α), extracellular signal-regulated kinase 1/2 (ERK1/2) and Notch1 signaling pathways were respectively investigated by immunofluorescence assay or western blotting in vivo and oxygen-glucose-deprived (OGD) brain microvascular endothelial cells (BMECs); simultaneously, wound healing of BMECs and tube formation assay were administrated. Compared to MCAo group, SSS extraction could significantly improve neurological functional scores, survival rate and cerebral infarct volume, enhance vWF + vascular density and perimeter, SDF-1α/CXCR4 axis, VEGF expression, as well as activate AKT/mTOR/HIF-1α and ERK1/2 and inhibit Notch1 pathways in penumbra. In vitro, containing SSS extraction serum increased BMEC migration, capillary formation and VEGF expression via up-regulations of AKT/mTOR and ERK1/2 pathways in OGD BMECs, but ERK inhibitor (U0126) reversed the result of VEGF expression in high dose of SSS group. Additionally, VEGFR2 and Notch1 expressions were suppressed by containing SSS extraction serum. All results were in dose dependent manner. Our study firstly demonstrates that SSS extraction is an angiogenic switch. Due to suppressed VEGFR2/Notch1 cascades and activated AKT/mTOR and ERK1/2 signals in BMECs, a feedback loop of angiogenic homeostasis is established. Furthermore, the comprehensive mediations of SDF-1α/CXCR4 axis, AKT/mTOR/HIF-α, ERK1/2 and Notch1 pathways in penumbra contribute to the improvements of neurological function, survival rate and infarct volume post-stroke. Copyright © 2018 Elsevier GmbH. All rights reserved.

A new shape for an old function: lasting effect of a physiologic surgical restoration of the left ventricle

PubMed Central

Cirillo, Marco; Amaducci, Andrea; Villa, Emmanuel; Tomba, Margherita Dalla; Brunelli, Federico; Mhagna, Zen; Troise, Giovanni; Quaini, Eugenio

2006-01-01

Background Long-term morphofunctional outcome may vary widely in surgical anterior left ventricular wall restoration, suggesting variability in post-surgical remodeling similar to that observed following acute myocardial infarction. The aim of this pilot study was to demonstrate that surgical restoration obtained with a particular shape of endoventricular patch leads to steady morphofunctional ventricular improvement when geometry, volume and residual akinesia can be restored as normal as possible. Methods This study involved 12 consecutive patients with previous anterior myocardial infarction, dilated cardiomyopathy and no mitral procedures, who underwent left ventricular reconstruction and coronary revascularization between May 2002 and May 2003 using a small, narrow, oval patch aiming at a volume ≤ 45 mL/m2 with elliptical shape. Eleven geometric parameters were examined preoperatively and at least 3, 12 and 24 months after the operation by serial echocardiographic studies and evaluated by paired t test taking the time of surgery as a starting point for remodeling. Results All patients were in NYHA class 1 at follow-up. Patch geometry obtained a conical shape of the ventricle with new apex, physiologic rearrangement of functioning myocardial wall and small residual akinesia. Ventricular changes at the four time-points showed that all parameters improved significantly compared to preoperative values (end-diastolic volume = 184.2 ± 23.9 vs 139.9 ± 22.0, p = 0.001; vs 151.0 ± 33.8, p = 0.06; vs 144.9 ± 34.0, p = 0.38; end-systolic volume = 125.7 ± 20.6 vs 75.2 ± 14.1, p = 0.001; vs 82.1 ± 23.9, p = 0,18; vs 77.1 ± 19.4, p = 0.41) without further changes during follow-up except for wall motion score index (2.0 ± 0.2 to 1.7 ± 0.2, to 1.4 ± 0.2, to 1.3 ± 0.2) and percentage of akinesia (30.4 ± 7.5 to 29.3 ± 4.2, to 19.8 ± 11.6, to 14.5 ± 7.2) which slowly and significantly improved suggesting a positive post-surgery remodeling. Conclusion Ventricular reconstruction caring of physiological shape, volume, revascularization and residual akinesia obtained a steady geometry. Positive remodeling and equalization of geometrical outcome may persistently prevent long-term redilation. PMID:17083734

Association of Blood Pressure Control Level With Left Ventricular Morphology and Function and With Subclinical Cerebrovascular Disease.

PubMed

Nakanishi, Koki; Jin, Zhezhen; Homma, Shunichi; Elkind, Mitchell S V; Rundek, Tatjana; Tugcu, Aylin; Sacco, Ralph L; Di Tullio, Marco R

2017-07-30

Left ventricular (LV) hypertrophy and subclinical cerebrovascular disease are early manifestations of cardiac and brain target organ damage caused by hypertension. This study aimed to investigate whether intensive office systolic blood pressure (SBP) control has beneficial effects on LV morphology and function and subclinical cerebrovascular disease in elderly patients with hypertension. We examined 420 patients treated for hypertension without history of heart failure and stroke from the CABL (Cardiovascular Abnormalities and Brain Lesions) study. All patients underwent 2-dimensional echocardiographic examination and brain magnetic resonance imaging. Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume. Patients were divided into 3 groups: SBP <120 mm Hg (intensive control); SBP 120 to 139 mm Hg (less intensive control); and SBP ≥140 mm Hg (uncontrolled). Prevalence of LV hypertrophy and diastolic dysfunction were lowest in the intensive control, intermediate in the less intensive control, and highest in the uncontrolled groups (12.8%, 31.8%, and 44.7%, respectively [ P <0.001], for LV hypertrophy; 46.8%, 61.7%, and 72.6%, respectively [ P =0.003], for diastolic dysfunction). Patients with less intensive SBP control had greater risk of LV hypertrophy than those with intensive control (adjusted odds ratio, 3.26; P =0.013). A similar trend was observed for LV diastolic dysfunction but did not reach statistical significance (adjusted odds ratio, 1.65; P =0.144). Conversely, intensive SBP control was not significantly associated with reduced risk of silent brain infarcts and white matter hyperintensity volume compared with less intensive control. Compared with less intensive control, intensive SBP control may have a stronger beneficial effect on cardiac than cerebral subclinical disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Inhibition of transient receptor potential vanilloid-1 confers neuroprotection, reduces tumor necrosis factor-alpha, and increases IL-10 in a rat stroke model.

PubMed

Hakimizadeh, Elham; Shamsizadeh, Ali; Roohbakhsh, Ali; Arababadi, Mohammad Kazemi; Hajizadeh, Mohammad R; Shariati, Mehdi; Rahmani, Mohammad R; Allahtavakoli, Mohammad

2017-08-01

Stroke is a major cause of mortality and long-term disability in adults. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke. Then, infarct volume, brain edema, body temperature, mRNA expression of TRPV1, and serum concentrations of tumor necrosis factor-alpha (TNF-α) and IL-10 were measured. Compared to the vehicle group, AMG9810 significantly decreased the infarct volume (P < 0.01). Latency for the removal of sticky labels from the forepaw and the hanging time were significantly decreased and increased, respectively, following administration of AMG9810 (P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV1 was significantly increased in vehicle group (P < 0.01). Administration of AMG9810 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P < 0.05). Moreover, our results indicate that AMG9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG9810 in reducing inflammation after stroke and imply that TRPV1 could be a potential target for the treatment of ischemic stroke. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Alternative complement pathway activation during invasive coronary procedures in acute myocardial infarction and stable angina pectoris.

PubMed

Horváth, Zsófia; Csuka, Dorottya; Vargova, Katarina; Kovács, Andrea; Leé, Sarolta; Varga, Lilian; Préda, István; Tóth Zsámboki, Emese; Prohászka, Zoltán; Kiss, Róbert Gábor

2016-12-01

The effect of invasive percutaneous coronary procedures on complement activation has not been elucidated. We enrolled stable angina patients with elective percutaneous coronary intervention (SA-PCI, n=24), diagnostic coronary angiography (CA, n=52) and 23 patients with ST segment elevation myocardial infarction and primary PCI (STEMI-PCI). Complement activation products (C1rC1sC1inh, C3bBbP and SC5b-9) were measured on admission, 6 and 24h after coronary procedures. The alternative pathway product, C3bBbP significantly and reversibly increased 6h after elective PCI (baseline: 7.81AU/ml, 6h: 16.09AU/ml, 24h: 4.27AU/ml, p<0.01, n=23) and diagnostic angiography (baseline: 6.13AU/ml, 6h: 12.08AU/ml, 24h: 5.4AU/ml, p<0.01, n=52). Six hour C3bBbP values correlated with post-procedural CK, creatinine level and the applied contrast material volume (r=0.41, r=0.4, r=0.3, p<0.05, respectively). In STEMI-PCI, baseline C3bBbP level was higher, compared to SA-PCI or CA patients (11.33AU/ml vs. 7.81AU/ml or 6.13AU/ml, p<0.001). Similarly, the terminal complex (SC5b-9) level was already elevated at baseline compared to SA-PCI group (3.49AU/ml vs. 1.87AU/ml, p=0.011). Complement pathway products did not increase further after primary PCI. Elective coronary procedures induced transient alternative complement pathway activation, influenced by the applied contrast volume. In STEMI, the alternative complement pathway is promptly activated during the atherothrombotic event and PCI itself had no further detectable effect. Copyright © 2016 Elsevier B.V. All rights reserved.

Docosahexaenoic acid complexed to albumin provides neuroprotection after experimental stroke in aged rats.

PubMed

Eady, Tiffany N; Khoutorova, Larissa; Obenaus, Andre; Mohd-Yusof, Alena; Bazan, Nicolas G; Belayev, Ludmila

2014-02-01

Recently we have shown that docosahexaenoic acid complexed to albumin (DHA-Alb) is neuroprotective after experimental stroke in young rats. The purpose of this study was to determine whether treatment with DHA-Alb would be protective in aged rats after focal cerebral ischemia. Isoflurane/nitrous oxide-anesthetized normothermic (brain temperature 36-36.5°C) Sprague-Dawley aged rats (18-months old) received 2h middle cerebral artery occlusion (MCAo) by poly-l-lysine-coated intraluminal suture. The neurological status was evaluated during occlusion (60min) and on days 1, 2, 3 and 7 after MCAo; a grading scale of 0-12 was employed. DHA (5mg/kg), Alb (0.63g/kg), DHA-Alb (5mg/kg+0.63g/kg) or saline was administered i.v. 3h after onset of stroke (n=8-10 per group). Ex vivo T2-weighted imaging (T2WI) of the brains was conducted on an 11.7T MRI on day 7 and 3D reconstructions were generated. Infarct volumes and number of GFAP (reactive astrocytes), ED-1 (activated microglia/microphages), NeuN (neurons)-positive cells and SMI-71 (positive vessels) were counted in the cortex and striatum at the level of the central lesion. Physiological variables were entirely comparable between groups. Animals treated with DHA-Alb showed significantly improved neurological scores compared to vehicle rats; 33% improvement on day 1; 39% on day 2; 41% on day 3; and 45% on day 7. Total and cortical lesion volumes computed from T2WI were significantly reduced by DHA-Alb treatment (62 and 69%, respectively). In addition, treatment with DHA-Alb reduced cortical and total brain infarction while promoting cell survival. We conclude that DHA-Alb therapy is highly neuroprotective in aged rats following focal cerebral ischemia and has potential for the effective treatment of ischemic stroke in aged individuals. © 2013. Published by Elsevier Inc. All rights reserved.

Culprit lesion thrombus burden after manual thrombectomy or percutaneous coronary intervention-alone in ST-segment elevation myocardial infarction: the optical coherence tomography sub-study of the TOTAL (ThrOmbecTomy versus PCI ALone) trial.

PubMed

Bhindi, Ravinay; Kajander, Olli A; Jolly, Sanjit S; Kassam, Saleem; Lavi, Shahar; Niemelä, Kari; Fung, Anthony; Cheema, Asim N; Meeks, Brandi; Alexopoulos, Dimitrios; Kočka, Viktor; Cantor, Warren J; Kaivosoja, Timo P; Shestakovska, Olga; Gao, Peggy; Stankovic, Goran; Džavík, Vladimír; Sheth, Tej

2015-08-01

Manual thrombectomy has been proposed as a strategy to reduce thrombus burden during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the effectiveness of manual thrombectomy in reducing thrombus burden is uncertain. In this substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial, we compared the thrombus burden at the culprit lesion using optical coherence tomography (OCT) in patients treated with thrombectomy vs. PCI-alone. The TOTAL trial (N = 10 732) was an international, multicentre, randomized trial of thrombectomy (using the Export catheter, Medtronic Cardiovascular, Santa Rosa, CA, USA) in STEMI patients treated with primary PCI. The OCT substudy prospectively enrolled 214 patients from 13 sites in 5 countries. Optical coherence tomography was performed immediately after thrombectomy or PCI-alone and then repeated after stent deployment. Thrombus quantification was performed by an independent core laboratory blinded to treatment assignment. The primary outcome of pre-stent thrombus burden as a percentage of segment analysed was 2.36% (95% CI: 1.73-3.22) in the thrombectomy group and 2.88% (95% CI: 2.12-3.90) in the PCI-alone group (P = 0.373). Absolute pre-stent thrombus volume was not different (2.99 vs. 3.74 mm(3), P = 0.329). Other secondary outcomes of pre-stent quadrants of thrombus, post-stent atherothrombotic burden, and post-stent atherothrombotic volume were not different between groups. Manual thrombectomy did not reduce pre-stent thrombus burden at the culprit lesion compared with PCI-alone. Both strategies were associated with low thrombus burden at the lesion site after the initial intervention to restore flow. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury.

PubMed

Wang, Yanzhe; He, Zhiyi; Deng, Shumin

2016-01-01

Activators of PPARs, particularly PPARγ, may be effective neuroprotective drugs against inflammatory responses in cerebral ischemia and reperfusion injury. Ursolic acid (UA) may act as a PPARγ agonist and serve as an anti-inflammatory agent. In this study, we used a rat middle cerebral artery occlusion and reperfusion model to examine how UA acts as a neuroprotective agent to modulate the metalloprotease/anti-metalloprotease balance. The middle cerebral artery occlusion and reperfusion model (occlusion for 2 hours followed by reperfusion for 48 hours) was induced in male Sprague Dawley rats. UA was administered intragastrically 0.5, 24, and 47 hours after reperfusion. Bisphenol A diglycidyl ether (a PPARγ antagonist) was intraperitoneally administered 1, 24.5, and 47.5 hours after reperfusion. Forty-eight hours after reperfusion, neurological deficits and infarct volume were estimated. The PPARγ level and the metalloprotease/anti-metalloprotease balance were examined by Western blotting and immunohistochemistry. The activation of MAPK signaling pathways was also assessed. UA-treated (5, 10, or 20 mg/kg) rats showed significant improvement in neurological deficit score, infarct volume, and the number of intact neurons compared with control rats (P<0.01). Both the PPARγ protein level and the percentage of PPARγ-positive cells were increased in the UA-treated groups (P<0.01). Compared with the control group, the UA-treated groups exhibited reduced protein levels of MMP2, MMP9, and activated MAPKs (P<0.01) but an increased level of TIMP1 (P<0.01). UA exerted its protective effects in a dose-dependent manner. Co-treatment with UA and bisphenol A diglycidyl ether completely abolished the UA-induced changes in PPARγ expression; however UA continued to exert a significant but partial neuroprotective effect. UA can act as a PPARγ agonist to improve the metalloprotease/anti-metalloprotease balance, possibly by inhibiting the activation of the MAPK signaling pathway, thereby attenuating cerebral ischemia and reperfusion injury. Therefore, UA may serve as a novel neuroprotective therapeutic agent.

Nonbinary quantification technique accounting for myocardial infarct heterogeneity: Feasibility of applying percent infarct mapping in patients.

PubMed

Mastrodicasa, Domenico; Elgavish, Gabriel A; Schoepf, U Joseph; Suranyi, Pal; van Assen, Marly; Albrecht, Moritz H; De Cecco, Carlo N; van der Geest, Rob J; Hardy, Rayphael; Mantini, Cesare; Griffith, L Parkwood; Ruzsics, Balazs; Varga-Szemes, Akos

2018-02-15

Binary threshold-based quantification techniques ignore myocardial infarct (MI) heterogeneity, yielding substantial misquantification of MI. To assess the technical feasibility of MI quantification using percent infarct mapping (PIM), a prototype nonbinary algorithm, in patients with suspected MI. Prospective cohort POPULATION: Patients (n = 171) with suspected MI referred for cardiac MRI. Inversion recovery balanced steady-state free-precession for late gadolinium enhancement (LGE) and modified Look-Locker inversion recovery (MOLLI) T 1 -mapping on a 1.5T system. Infarct volume (IV) and infarct fraction (IF) were quantified by two observers based on manual delineation, binary approaches (2-5 standard deviations [SD] and full-width at half-maximum [FWHM] thresholds) in LGE images, and by applying the PIM algorithm in T 1 and LGE images (PIM T1 ; PIM LGE ). IV and IF were analyzed using repeated measures analysis of variance (ANOVA). Agreement between the approaches was determined with Bland-Altman analysis. Interobserver agreement was assessed by intraclass correlation coefficient (ICC) analysis. MI was observed in 89 (54.9%) patients, and 185 (38%) short-axis slices. IF with 2, 3, 4, 5SDs and FWHM techniques were 15.7 ± 6.6, 13.4 ± 5.6, 11.6 ± 5.0, 10.8 ± 5.2, and 10.0 ± 5.2%, respectively. The 5SD and FWHM techniques had the best agreement with manual IF (9.9 ± 4.8%) determination (bias 1.0 and 0.2%; P = 0.1426 and P = 0.8094, respectively). The 2SD and 3SD algorithms significantly overestimated manual IF (9.9 ± 4.8%; both P < 0.0001). PIM LGE measured significantly lower IF (7.8 ± 3.7%) compared to manual values (P < 0.0001). PIM LGE , however, showed the best agreement with the PIM T1 reference (7.6 ± 3.6%, P = 0.3156). Interobserver agreement was rated good to excellent for IV (ICCs between 0.727-0.820) and fair to good for IF (0.589-0.736). The application of the PIM LGE technique for MI quantification in patients is feasible. PIM LGE , with its ability to account for voxelwise MI content, provides significantly smaller IF than any thresholding technique and shows excellent agreement with the T 1 -based reference. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Comparative functional MRI study to assess brain activation upon active and passive finger movements in patients with cerebral infarction.

PubMed

Fu, Yue; Zhang, Quan; Zhang, Jing; Zhang, Yun Ting

2015-01-01

To compare the effects of active and passive movements on brain activation in patients with cerebral infarction using fMRI. Twenty-four hemiplegic patients with cerebral infarction were evaluated using fMRI. All patients performed active and passive finger opposition movements. Patients were instructed to perform the finger opposition movement for the active movement task. For the passive movement task, the subject's fingers were moved by the examiner to perform the finger opposition movement. Statistical parametric mapping software was used for statistical analyses and to process all data. In the affected hemisphere, sensorimotor cortex (SMC) activation intensity and range were significantly stronger during the passive movement of the affected fingers compared to the active movement of the affected fingers (p < 0.05). However, there were no significant differences between active and passive movements of unaffected fingers in SMC activation intensity and range in the unaffected hemisphere (p > 0.05). In addition, the passive movement activated many other regions of the brain. The brain regions activated by passive movements of the affected fingers tended to center toward the contralateral SMC. Our findings suggest that passive movements induce cortical reorganization in patients with cerebral infarction. Therefore, passive movement is likely beneficial for motor function recovery in patients with cerebral infarction.

Anticoagulation therapy is harmful to large-sized cerebellar infarction.

PubMed

Zhang, She-Qing; Wang, Wei; Ma, Xiao-Long; Xia, Yu-Ye; Liu, Ai-Jun

2014-09-01

Anticoagulants are commonly used to treat ischemic stroke. Its impact on cerebellar infarction has not been fully understood. In the clinical study, we reviewed a consecutive series of patients with large-sized cerebellar infarction (diameter > 3 cm, n = 30) treated with or without anticoagulation. In animal study, cerebellar infarction operation was performed in 12 Cynomolgus monkeys. Then the animals were administrated with low molecular weight heparin (LMWH) or vehicle for 14 days. Six patients died during the following treatment. All the subjects that died received anticoagulation therapy, while nobody in the survival group received such a therapy. Compared with sham-operated animals, all monkeys with cerebellar infarction have obvious neurological deficits. The number and size of the Purkinje cells in the cerebellar area were also reduced. Two animals in the LMWH group (33%) died, while all animals in the vehicle control group survived. Compared with the vehicle group, the neurological score in the LMWH group was significantly increased (P < 0.05). The water content in the cerebella was also significantly higher (P < 0.05). Edema, hemorrhage, and subarachnoid hemorrhage occurred in the cerebella as well as brainstem of all the LMWH treated animals. These results indicated the harmful effects of anticoagulation therapy on large-sized cerebellar infarction. © 2014 John Wiley & Sons Ltd.

The protective effect of fasudil pretreatment combined with ischemia postconditioning on myocardial ischemia/reperfusion injury in rats.

PubMed

Li, W-N; Wu, N; Shu, W-Q; Guan, Y-E; Jia, D-L

2014-01-01

Ischemic postconditioning (IPO) and pharmacological pretreatment may reduce myocardial necrosis and apoptosis during ischemia/reperfusion. This study aimed to determine the protective effect of fasudil pretreatment combined with IPO on myocardial ischemia/reperfusion injury in rats and explore the possible mechanisms. The SD rats were induced by intraperitoneal injection of fasudil hydrochloride (1 or 10 mg/kg) 60 min before the initiation of ischemia, while the control rats were given the same volume of saline. The hearts were hung on the Langendorff perfusion apparatus and underwent 30 min global ischemia and 120 min reperfusion. The IPO protocol was induced by six cycles of 10 sec ischemia and 10 sec reperfusion at the onset of reperfusion. The hemodynamic changes were measured, myocardial infarct size was determined by triphenyltetrazolium chloride (TTC) staining, cardiomyocyte apoptosis was detected by TUNEL staining, lactate dehydrogenase (LDH) was analyzed from coronary effluents, phosphorylation of Akt and eNOS, as well as expression of Bcl-2 and Bax were measured by western blotting analysis. The high-dose fasudil (10 mg/kg) pretreatment group and IPO group significantly improved post-ischemia cardiac function, reduced myocardial infarct size, attenuated cardiomyocyte apoptosis, decreased the release of LDH, increased expression of phospho-Akt, phospho-eNOS and Bcl-2, and reduced expression of Bax compared with the control group (p < 0.05). In addition, the high-dose fasudil pretreatment combined with IPO group could further improved post-ischemia cardiac function, reduced myocardial infarct size, attenuated cardiomyocyte apoptosis, decreased the release of LDH, increased expression of phospho-Akt, phospho-eNOS and Bcl-2, and reduced expression of Bax compared with the single treatment groups (p < 0.05). The combination of high-dose fasudil pretreatment and IPO had a synergistic protective effect on myocardial ischemia/reperfusion injury, which was mediated via upregulating the PI3K/Akt/eNOS pathway, increasing expression of antiapoptotic Bcl-2, and decreasing expression of proapoptotic Bax.

Clinical features and the degree of cerebrovascular stenosis in different types and subtypes of cerebral watershed infarction.

PubMed

Li, Yue; Li, Man; Zhang, Xiaoyu; Yang, Shuna; Fan, Huimin; Qin, Wei; Yang, Lei; Yuan, Junliang; Hu, Wenli

2017-08-29

Whether there are differences in pathogenesis among different types and subtypes of cerebral watershed infarction (WSI) is controversial since they have been combined into a single group in most previous studies. We prospectively identified 340 supratentorial WSI patients at Beijing Chao-Yang Hospital, Capital Medical University, China and classified them based on diffusion-weighted imaging(DWI) templates. Baseline characteristics, clinical courses and neuroradiological features were compared among patients with different types and subtypes of WSI. We identified 92 patients with cortical watershed infarction (CWI), 112 with internal watershed infarction (IWI) and 136 with mixed-type infarction. Compared with CWI patients, more IWI patients had critical stenosis of internal carotid artery (ICA) (P < 0.001). For the CWI group, patients with anterior watershed infarction (AWI) were more prone to critical ICA stenosis than those with posterior watershed infarction (PWI) (P = 0.011). For the IWI group, critical ICA stenosis was more prevalent in patients with partial IWI (P-IWI) than in those with confluent IWI (C-IWI) (P = 0.026). IWI patients were more frequently found to have clinical deterioration during the first 7 days of hospitalization and a poor prognosis at the 90th day than in CWI patients (P = 0.003 and P = 0.014, respectively). IWI, especially the P-IWI subtype, is associated with hemodynamic impairment (HDI), whereas CWI has a weaker correlation with ICA steno-occlusion. Furthermore, IWI patients are more prone to poor prognosis.

Renal sympathetic denervation suppresses atrial fibrillation induced by acute atrial ischemia/infarction through inhibition of cardiac sympathetic activity.

PubMed

Zhou, Qina; Zhou, Xianhui; TuEr-Hong, ZuKe-la; Wang, Hongli; Yin, Tingting; Li, Yaodong; Zhang, Ling; Lu, Yanmei; Xing, Qiang; Zhang, Jianghua; Yang, Yining; Tang, Baopeng

2016-01-15

This study aims to explore the effects of renal sympathetic denervation (RSD) on atrial fibrillation (AF) inducibility and sympathetic activity induced by acute atrial ischemia/infarction. Acute ischemia/infarction was induced in 12 beagle dogs by ligating coronary arteries that supply the atria. Six dogs in the sham-RSD group did not undergo RSD, and six dogs without coronary artery ligation served as controls. AF induction rate, sympathetic discharge, catecholamine concentration and densities of tyrosine hydroxylase-positive nerves were measured. Acute atrial ischemia/infarction resulted in a significant increase of AF induction rate, which was decreased by RSD compared to controls (P<0.05). The root-mean-square peak value, peak area and number of sympathetic discharges were significantly augmented by atrial ischemia relative to the baseline and control (P<0.05). The number of sympathetic discharges was significantly reduced in the RSD group, compared to the control and sham-RSD groups (P<0.05). Norepinephrine and epinephrine concentrations in the atria, ventricle and kidney were elevated by atrial ischemia/infarction, but were reduced by RSD (P<0.05). Sympathetic hyperactivity was associated with pacing-induced AF after acute atrial ischemia/infarction. RSD has the potential to reduce the incidence of new-onset AF after acute atrial ischemia/infarction. The inhibition of cardiac sympathetic activity by RSD may be one of the major underlying mechanisms for the marked reduction of AF inducibility. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Myocardial infarction in Swedish subway drivers.

PubMed

Bigert, Carolina; Klerdal, Kristina; Hammar, Niklas; Gustavsson, Per

2007-08-01

Particulate matter in urban air is associated with the risk of myocardial infarction in the general population. Very high levels of airborne particles have been detected in the subway system of Stockholm, as well as in several other large cities. This situation has caused concern for negative health effects among subway staff. The aim of this study was to investigate whether there is an increased incidence of myocardial infarction among subway drivers. Data from a population-based case-control study of men aged 40-69 in Stockholm County in 1976-1996 were used. The study included all first events of myocardial infarction in registers of hospital discharges and deaths. The controls were selected randomly from the general population. National censuses were used for information on occupation. Altogether, 22 311 cases and 131 496 controls were included. Among these, 54 cases and 250 controls had worked as subway drivers. The relative risk of myocardial infarction among subway drivers was not increased. It was 0.92 [95% confidence interval (95% CI) 0.68-1.25] when the subway drivers were compared with other manual workers and 1.06 (95% CI 0.78-1.43) when the subway drivers were compared with all other gainfully employed men. Subgroup analyses indicated no influence on the risk of myocardial infarction from the duration of employment, latency time, or time since employment stopped. Subway drivers in Stockholm do not have a higher incidence of myocardial infarction than other employed persons.

Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats

PubMed Central

Wang, Ai-Hong; Ma, Qian; Wang, Xin; Xu, Gui-Hua

2018-01-01

Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke. PMID:29399121

Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats.

PubMed

Wang, Ai-Hong; Ma, Qian; Wang, Xin; Xu, Gui-Hua

2018-02-01

Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke.

Bedside diagnosis of mitochondrial dysfunction after malignant middle cerebral artery infarction.

PubMed

Nielsen, T H; Schalén, W; Ståhl, N; Toft, P; Reinstrup, P; Nordström, C H

2014-08-01

The study explores whether the cerebral biochemical pattern in patients treated with hemicraniectomy after large middle cerebral artery infarcts reflects ongoing ischemia or non-ischemic mitochondrial dysfunction. The study includes 44 patients treated with decompressive hemicraniectomy (DCH) due to malignant middle cerebral artery infarctions. Chemical variables related to energy metabolism obtained by microdialysis were analyzed in the infarcted tissue and in the contralateral hemisphere from the time of DCH until 96 h after DCH. Reperfusion of the infarcted tissue was documented in a previous report. Cerebral lactate/pyruvate ratio (L/P) and lactate were significantly elevated in the infarcted tissue compared to the non-infarcted hemisphere (p < 0.05). From 12 to 96 h after DCH the pyruvate level was significantly higher in the infarcted tissue than in the non-infarcted hemisphere (p < 0.05). After a prolonged period of ischemia and subsequent reperfusion, cerebral tissue shows signs of protracted mitochondrial dysfunction, characterized by a marked increase in cerebral lactate level with a normal or increased cerebral pyruvate level resulting in an increased LP-ratio. This biochemical pattern contrasts to cerebral ischemia, which is characterized by a marked decrease in cerebral pyruvate. The study supports the hypothesis that it is possible to diagnose cerebral mitochondrial dysfunction and to separate it from cerebral ischemia by microdialysis and bed-side biochemical analysis.

Tissue-Selective Salvage of the White Matter by Successful Endovascular Stroke Therapy.

PubMed

Kleine, Justus F; Kaesmacher, Mirjam; Wiestler, Benedikt; Kaesmacher, Johannes

2017-10-01

White matter (WM) is less vulnerable to ischemia than gray matter. In ischemic stroke caused by acute large-vessel occlusion, successful recanalization might therefore sometimes selectively salvage the WM, leading to infarct patterns confined to gray matter. This study examines occurrence, determinants, and clinical significance of such effects. Three hundred twenty-two patients with acute middle cerebral artery occlusion subjected to mechanical thrombectomy were included. Infarct patterns were categorized into WM - (sparing the WM) and WM + (involving WM). National Institutes of Health Stroke Scale-based measures of neurological outcome, including National Institutes of Health Stroke Scale improvement or National Institutes of Health Stroke Scale worsening, good functional midterm outcome (day 90-modified Rankin Scale score of ≤2), the occurrence of malignant swelling, and in-hospital mortality were predefined outcome measures. WM - infarcts occurred in 118 of 322 patients and were associated with successful recanalization and better collateral grades ( P <0.05). Shorter symptom-onset to recanalization times were also associated with WM - infarcts in univariate analysis, but not when adjusted for collateral grades. WM - infarcts were independently associated with good neurological outcome (adjusted odds ratio, 3.003; 95% confidence interval, 1.186-7.607; P =0.020) and good functional midterm outcome (adjusted odds ratio, 8.618; 95% confidence interval, 2.409-30.828; P =0.001) after correcting for potential confounders, including final infarct volume. Only 2.6% of WM - patients, but 20.5% of WM + patients exhibited neurological worsening, and none versus 12.8% developed malignant swelling ( P <0.001), contributing to lower mortality in this group (2.5% versus 10.3%; P =0.014). WM infarction commonly commences later than gray matter infarction after acute middle cerebral artery occlusion. Successful recanalization can therefore salvage completely the WM at risk in many patients even several hours after symptom onset. Preservation of the WM is associated with better neurological recovery, prevention of malignant swelling, and reduced mortality. This has important implications for neuroprotective strategies, and perfusion imaging-based patient selection, and provides a rationale for treating selected patients in extended time windows. © 2017 American Heart Association, Inc.

Different Causes of Death in Patients with Myocardial Infarction Type 1, Type 2, and Myocardial Injury.

PubMed

Lambrecht, Sascha; Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S; Gerke, Oke; Hosbond, Susanne; Diederichsen, Axel C P; Thygesen, Kristian; Mickley, Hans

2018-05-01

Data outlining the mortality and the causes of death in patients with type 1 myocardial infarction, type 2 myocardial infarction, and those with myocardial injury are limited. During a 1-year period from January 2010 to January 2011, all hospitalized patients who had cardiac troponin I measured on clinical indication were prospectively studied. Patients with at least one cardiac troponin I value >30 ng/L underwent case ascertainment and individual evaluation by an experienced adjudication committee. Patients were classified as having type 1 myocardial infarction, type 2 myocardial infarction, or myocardial injury according to the criteria of the universal definition of myocardial infarction. Follow-up was ensured until December 31, 2014. Data on mortality and causes of death were obtained from the Danish Civil Registration System and the Danish Register of Causes of Death. Overall, 3762 consecutive patients were followed for a mean of 3.2 years (interquartile range 1.3-3.6 years). All-cause mortality differed significantly among categories: Type 1 myocardial infarction 31.7%, type 2 myocardial infarction 62.2%, myocardial injury 58.7%, and 22.2% in patients with nonelevated troponin values (log-rank test; P < .0001). In patients with type 1 myocardial infarction, 61.3% died from cardiovascular causes, vs 42.6% in patients with type 2 myocardial infarction (P = .015) and 41.2% in those with myocardial injury (P < .0001). The overall mortality and the causes of death did not differ substantially between patients with type 2 myocardial infarction and those with myocardial injury. Patients with type 2 myocardial infarction and myocardial injury exhibit a significantly higher long-term mortality compared with patients with type 1 myocardial infarction . However, most patients with type 1 myocardial infarction die from cardiovascular causes in contrast to patients with type 2 myocardial infarction and myocardial injury, in whom noncardiovascular causes of death predominate. Copyright © 2018 Elsevier Inc. All rights reserved.

Fumarate decreases edema volume and improves functional outcome after experimental stroke.

PubMed

Clausen, Bettina Hjelm; Lundberg, Louise; Yli-Karjanmaa, Minna; Martin, Nellie Anne; Svensson, Martina; Alfsen, Maria Zeiler; Flæng, Simon Bertram; Lyngsø, Kristina; Boza-Serrano, Antonio; Nielsen, Helle H; Hansen, Pernille B; Finsen, Bente; Deierborg, Tomas; Illes, Zsolt; Lambertsen, Kate Lykke

2017-09-01

Oxidative stress and inflammation exacerbate tissue damage in the brain after ischemic stroke. Dimethyl-fumarate (DMF) and its metabolite monomethyl-fumarate (MMF) are known to stimulate anti-oxidant pathways and modulate inflammatory responses. Considering these dual effects of fumarates, we examined the effect of MMF treatment after ischemic stroke in mice. Permanent middle cerebral artery occlusion (pMCAO) was performed using adult, male C57BL/6 mice. Thirty minutes after pMCAO, 20mg/kg MMF was administered intravenously. Outcomes were evaluated 6, 24 and 48h after pMCAO. First, we examined whether a bolus of MMF was capable of changing expression of kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor (Nrf)2 in the infarcted brain. Next, we studied the effect of MMF on functional recovery. To explore mechanisms potentially influencing functional changes, we examined infarct volumes, edema formation, the expression of heat shock protein (Hsp)72, hydroxycarboxylic acid receptor 2 (Hcar2), and inducible nitric oxide synthase (iNOS) in the infarcted brain using real-time PCR and Western blotting. Concentrations of a panel of pro- and anti-inflammatory cytokines (IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, TNF) were examined in both the infarcted brain tissue and plasma samples 6, 24 and 48h after pMCAO using multiplex electrochemoluminiscence analysis. Administration of MMF increased the protein level of Nrf2 6h after pMCAO, and improved functional outcome at 24 and 48h after pMCAO. MMF treatment did not influence infarct size, however reduced edema volume at both 24 and 48h after pMCAO. MMF treatment resulted in increased Hsp72 expression in the brain 6h after pMCAO. Hcar2 mRNA levels increased significantly 24h after pMCAO, but were not different between saline- and MMF-treated mice. MMF treatment also increased the level of the anti-inflammatory cytokine IL-10 in the brain and plasma 6h after pMCAO, and additionally reduced the level of the pro-inflammatory cytokine IL-12p70 in the brain at 24 and 48h after pMCAO. A single intravenous bolus of MMF improved sensory-motor function after ischemic stroke, reduced edema formation, and increased the levels of the neuroprotective protein Hsp72 in the brain. The early increase in IL-10 and reduction in IL-12p70 in the brain combined with changes in systemic cytokine levels may also contribute to the functional recovery after pMCAO. Copyright © 2017. Published by Elsevier Inc.

Impairment of facial recognition in patients with right cerebral infarcts quantified by computer aided "morphing".

PubMed Central

Rösler, A; Lanquillon, S; Dippel, O; Braune, H J

1997-01-01

OBJECTIVE: To investigate where facial recognition is located anatomically and to establish whether there is a graded transition from unimpaired recognition of faces to complete prosopagnosia after infarctions in the territory of the middle cerebral artery. METHODS: A computerised morphing program was developed which shows 30 frames gradually changing from portrait photographs of unfamiliar persons to those of well known persons. With a standardised protocol, 31 patients with right and left sided infarctions in the territory of the middle cerebral artery and an age and sex matched control group were compared by non-parametric tests. RESULTS AND CONCLUSION: Facial recognition in patients with right sided lesions was significantly impaired compared with controls and with patients with left sided lesions. A graded impairment in facial recognition in patients with right sided ischaemic infarcts in the territory of the middle cerebral artery seems to exist. Images PMID:9069481

Autonomic responses during acute myocardial infarction in the rat model: implications for arrhythmogenesis.

PubMed

Kolettis, Theofilos M; Kontonika, Marianthi; Lekkas, Panagiotis; Vlahos, Antonios P; Baltogiannis, Giannis G; Gatzoulis, Konstantinos A; Chrousos, George P

2018-04-10

Autonomic responses participate in the pathophysiology of acute myocardial infarction, but their precise time course remains unclear. Here, we investigated the autonomic activity and ventricular tachyarrhythmias in conscious, unrestrained rats post-infarction. The left coronary artery was ligated in 12 Wistar rats, and six rats were sham operated, followed by 24-h electrocardiographic recording via implanted telemetry transmitters. Sympathetic activity was assessed by detrended fluctuation analysis and vagal activity by time- and frequency-domain analysis of heart rate variability. The duration of the ventricular tachyarrhythmias was measured, and voluntary motion served as a marker of heart failure. In sham-operated rats, heart rate and sympathetic activity remained low, whereas vagal activity rose progressively after the fourth hour. Post-ligation, medium-sized antero-septal necrosis was observed, reaching ~20% of the left ventricular volume; tachyarrhythmias were frequent, displaying a bimodal curve, and motion counts were low. Vagal activity decreased early post-ligation, coinciding with a high incidence of tachyarrhythmias, but tended to rise subsequently in rats with higher motion counts. Sympathetic activity increased after the third hour, along with a second tachyarrhythmia peak, and remained elevated throughout the 24-h period. Vagal withdrawal, followed by gradual sympathetic activation, may participate in arrhythmogenesis during acute myocardial infarction.

Diagnosis and management of ST elevation myocardial infarction: a review of the recent literature and practice guidelines.

PubMed

Hahn, Sigrid A; Chandler, Charles

2006-01-01

There is a large volume of literature available to guide the peri-infarct management of ST elevation myocardial infarction (STEMI). Most of this literature focuses on improving the availability and efficacy of reperfusion therapy. The purpose of this article is to review contemporary scientific evidence and guideline recommendations regarding the diagnosis and therapy of STEMI. Studies and epidemiological data were identified using Medline, the Cochrane Database, and an Internet search engine. Medline was searched for landmark and recent publications using the following key words: STEMI, guidelines, epidemiology, reperfusion, fibrinolytics, percutaneous coronary intervention (PCI), facilitated PCI, transfer, delay, clopidogrel, glycoprotein IIb/IIIa, low-molecular-weight heparin (LMWH), beta-blockers, nitrates, and angiotensin-converting enzyme (ACE) inhibitors. The data accessed indicate that urgent reperfusion with either fibrinolytics or percutaneous intervention should be considered for every patient having symptoms of myocardial infarction with ST segment elevation or a bundle branch block. The utility of combined mechanical and pharmacological reperfusion is currently under investigation. Ancillary treatments may utilize clopidogrel, glycoprotein IIb/IIIa inhibitors, or low molecular weight heparin, depending on the primary reperfusion strategy used. Comprehensive clinical practice guidelines incorporate much of the available contemporary evidence, and are important resources for the evidence-based management of STEMI.

Reduced Lung Function and Cerebral Small Vessel Disease in Japanese Men: the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).

PubMed

Seto-Yukimura, Ruriko; Ogawa, Emiko; Hisamatsu, Takashi; Torii, Sayuki; Shiino, Akihiko; Nozaki, Kazuhiko; Fujiyoshi, Akira; Miura, Katsuyuki; Nakano, Yasutaka; Ueshima, Hirotsugu

2018-02-16

We aimed to investigate the association between reduced lung function and cerebral small vessel diseases via cranial magnetic resonance imaging (MRI) in the cross-sectional study of the general Japanese population. We recruited participants aged ≥40 years from the general population of a single city in Japan. We clarified the comorbidities and treatments, smoking habits, second-hand smoke exposure, current alcohol consumption, education level, exercise habits, and occupation. The pulmonary function test was performed to assess the forced expiratory volume in 1 second (FEV 1 ) % predicted and forced vital capacity (FVC) % predicted values. Cranial MRI was performed to evaluate the white matter lesions (WMLs) and lacunar infarcts. We examined the association of the WMLs and lacunar infarcts with a 1-standard deviation (SD) lower in the FEV 1 % predicted and FVC % predicted, on the basis of the smoking status. A total of 473 men were examined. The association of WMLs and lacunar infarcts with the spirometry-based indices were significant only in never smokers. The association between lung function impairment and cerebral small vessel disease did not change after further adjusting for second-hand smoke exposure. In a community-based sample of Japanese men, we found an association between reduced lung function and WMLs and lacunar infarcts in never smokers.

Epicardial adipose tissue density and volume are related to subclinical atherosclerosis, inflammation and major adverse cardiac events in asymptomatic subjects.

PubMed

Goeller, Markus; Achenbach, Stephan; Marwan, Mohamed; Doris, Mhairi K; Cadet, Sebastien; Commandeur, Frederic; Chen, Xi; Slomka, Piotr J; Gransar, Heidi; Cao, J Jane; Wong, Nathan D; Albrecht, Moritz H; Rozanski, Alan; Tamarappoo, Balaji K; Berman, Daniel S; Dey, Damini

We investigated whether epicardial adipose tissue (EAT) volume and density are related to early atherosclerosis, plaque inflammation and major adverse cardiac events (MACE, cardiac death and myocardial infarction) in asymptomatic subjects. EAT volume and density were quantified from non-contrast cardiac CT in 456 asymptomatic individuals (age 60.3 ± 8.3; 68% with CCS>0) from the prospective EISNER trial. EAT volume and density were examined in relation to coronary calcium score (CCS), inflammatory biomarkers and MACE. EAT volume was higher and EAT density lower in subjects with coronary calcium compared to subjects without [89 vs 74 cm 3 , p < 0.001] [-76.9 vs -75.7 HU,p = 0.024]. EAT volume was lowest in individuals with no coronary calcium and was significant higher in subjects with early atherosclerosis (CCS 1-99) [74 vs 87 cm 3 ,p = 0.016] and in subjects with more advanced atherosclerosis (CCS≥100) [89 cm 3 ,p = 0.002]). EAT volume was independently related to serum levels of PAI-1, and MCP-1 and inversely related to adiponectin and HDL-cholesterol (p < 0.05). EAT density was inversely related to PAI-1 and LDL-cholesterol and positively associated to adiponectin, sICAM-1 and HDL-cholesterol (p < 0.05). EAT density was more significantly associated with MACE [(HR 0.8, 95%CI:0.7-0.98), p = 0.029] than EAT volume or CCS. EAT volume was higher and density lower in subjects with coronary calcium compared to subjects with CCS = 0, with similar EAT volume in CCS<100 and CCS≥100. Lower EAT density and increased EAT volume were associated with coronary calcification, serum levels of plaque inflammatory markers and MACE, suggesting that dysfunctional EAT may be linked to early plaque formation and inflammation. Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor {kappa}B p65 activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xue, Xia; Center for New Drugs Evaluation, Shandong University, Jinan 250012; Qu, Xian-Jun

Research highlights: {yields} Permanent NF-{kappa}B p65 activation contributes to the infarction after ischemia-reperfusion injury in rats. {yields} Baicalin can markedly inhibit the nuclear NF-{kappa}B p65 expression and m RNA levels after ischemia-reperfusion injury in rats. {yields} Baicalin decreased the cerebral infarction area via inhibiting the activation of nuclear NF-{kappa}B p65. -- Abstract: Baicalin is a flavonoid compound purified from plant Scutellaria baicalensis Georgi. We aimed to evaluate the neuroprotective effects of baicalin against cerebral ischemic reperfusion injury. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. Baicalin at dosesmore » of 50, 100 and 200 mg/kg was intravenously injected after ischemia onset. Twenty-four hours after reperfusion, the neurological deficit was scored and infarct volume was measured. Hematoxylin and eosin (HE) staining was performed to analyze the histopathological changes of cortex and hippocampus neurons. We examined the levels of NF-{kappa}B p65 in ischemic cortexes by Western blot analysis and RT-PCR assay. The results showed that the neurological deficit scores were significantly decreased from 2.0 {+-} 0.7 to 1.2 {+-} 0.4 and the volume of infarction was reduced by 25% after baicalin injection. Histopathological examination showed that the increase of neurons with pycnotic shape and condensed nuclear in cortex and hippocampus were not observed in baicalin treated animals. Further examination showed that NF-{kappa}B p65 in cortex was increased after ischemia reperfusion injury, indicating the molecular mechanism of ischemia reperfusion injury. The level of NF-{kappa}B p65 was decreased by 73% after baicalin treatment. These results suggest that baicalin might be useful as a potential neuroprotective agent in stroke therapy. The neuroprotective effects of baicalin may relate to inhibition of NF-{kappa}B p65.« less

Effects of the combined treatment of bone marrow stromal cells with mild exercise and thyroid hormone on brain damage and apoptosis in a mouse focal cerebral ischemia model.

PubMed

Akhoundzadeh, Kobar; Vakili, Abedin; Sameni, Hamid Reza; Vafaei, Abbas Ali; Rashidy-Pour, Ali; Safari, Manouchehr; Mohammadkhani, Razieh

2017-08-01

This study examined whether post-stroke bone marrow stromal cells (BMSCs) therapy combined with exercise (EX) and/or thyroid hormone (TH) could reduce brain damage in an experimental ischemic stroke in mice. Focal cerebral ischemia was induced under Laser Doppler Flowmetry (LDF) guide by 45 min of middle cerebral artery occlusion (MCAO), followed by 7 days of reperfusion in albino mice. BMSCs were injected into the right cerebral ventricle 24 h after MCAO, followed by daily injection of T3 (20 μg/100 g weight S.C) and 6 days of running on a treadmill. Infarct size, neurobehavioral test, TUNEL and BrdU positive cells were evaluated at 7 days after MCAO. Treatment with BMSCs and mild EX alone significantly reduced the infarct volume by 23% and 44%, respectively (both, p < 0.001). The BMSCs + TH, BMSCs + EX, and BMSCs + EX + TH combination therapies significantly reduced the infarct volume by 26%, 51%, and 70%, respectively (all, p < 0.001). A significant improvement in the neurobehavioral functioning was observed in the EX, BMSCs + EX, and BMSCs + EX+ TH groups (p < 0.001). The number of TUNEL-positive cells (a marker of apoptosis) was significantly reduced in the EX, BMSCs, BMSCs + EX, BMSCs + TH, and BMSCs + EX + TH groups (all, p < 0.001). Moreover, the combination therapy considerably increased BrdU-labeled cells in the subventricular zone (SVZ) (p < 0.01). Our findings indicated that the combined treatment of BMSCs with mild EX and TH more efficiently reduces the cerebral infarct size after stroke. More likely, these effects mediate via enchaining generation of new neuronal cells and the attenuation of apoptosis in ischemia stroke in young mice.

Time-Dependent Computed Tomographic Perfusion Thresholds for Patients With Acute Ischemic Stroke.

PubMed

d'Esterre, Christopher D; Boesen, Mari E; Ahn, Seong Hwan; Pordeli, Pooneh; Najm, Mohamed; Minhas, Priyanka; Davari, Paniz; Fainardi, Enrico; Rubiera, Marta; Khaw, Alexander V; Zini, Andrea; Frayne, Richard; Hill, Michael D; Demchuk, Andrew M; Sajobi, Tolulope T; Forkert, Nils D; Goyal, Mayank; Lee, Ting Y; Menon, Bijoy K

2015-12-01

Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times. Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion-weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. Tmax, cerebral blood flow, and cerebral blood volume derived from delay-insensitive CTP postprocessing were analyzed using receiver-operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time. One hundred and thirty-two patients were included. Tmax thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL·min(-1)·100 g(-1) were associated with infarct if reperfused <90 min from CTP with onset <180 min. The discriminative ability of cerebral blood volume was modest. No statistically significant relationship was noted between stroke onset-to-CTP time and the optimal CTP thresholds for all parameters based on discrete or continuous time analysis (P>0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow (P<0.001; r=0.59 and 0.77 for gray and white matter, respectively) and Tmax (P<0.001; r=-0.68 and -0.60 for gray and white matter, respectively) parameters. Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion. © 2015 American Heart Association, Inc.

Myocardial infarction false alarm: initial electrocardiogram and cardiac enzymes.

PubMed

Gupta, Esha Das; Sakthiswary, Rajalingham

2014-05-01

The objectives of this study were to determine the incidence of a myocardial infarction "false alarm" and evaluate the efficacy of the initial electrocardiogram and cardiac enzymes in diagnosing myocardial infarction in Malaysia. We recruited patients who were admitted with suspected myocardial infarction from June to August 2008. The medical records of these patients were reviewed for the initial electrocardiogram, initial cardiac enzyme levels (creatinine kinase-MB and troponin T), and the final diagnosis upon discharge. The subjects were stratified into 2 groups: true myocardial infarction, and false alarm. 125 patients were enrolled in this study. Following admission and further evaluation, the diagnosis was revised from myocardial infarction to other medical conditions in 48 (38.4%) patients. The sensitivity and specificity of the initial ischemic electrocardiographic changes were 54.5% and 70.8%, respectively. Raised cardiac enzymes had a sensitivity of 44.3% and specificity of 95.8%. A significant proportion of patients in Malaysia are admitted with a false-alarm myocardial infarction. The efficacy of the electrocardiogram in diagnosing myocardial infarction in Malaysia was comparable to the findings of Western studies, but the cardiac enzymes had a much lower sensitivity.

Acute sleep deprivation preconditions the heart against ischemia/ reperfusion injury: the role of central GABA-A receptors

PubMed Central

Parsa, Hoda; Imani, Alireza; Faghihi, Mahdieh; Riahi, Esmail; Badavi, Mohammad; Shakoori, Abbas; Rastegar, Tayebeh; Aghajani, Marjan; Rajani, Sulail Fatima

2017-01-01

Objective(s): Central γ-aminobutyric acid (GABA) neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD) affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI), and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA) by assessing nitric oxide (NO) and oxidative stress. Materials and Methods: The CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist) administration. All animals underwent 30 min of coronary occlusion (ischemia), followed by 2 hr reperfusion (IR). The five experimental groups (n=12) included are as follows: IR: received saline; BIC+IR: received Bicuculline; MLP+IR: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD+IR: underwent ASD in an aquarium with multiple small platforms; and BIC+ASD+IR: received bicuculline prior to ASD. Results: Bicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS) gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BIC+ASD+IR as compared to the ASD+IR group. Conclusion: Blockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production. PMID:29299201

Acute sleep deprivation preconditions the heart against ischemia/ reperfusion injury: the role of central GABA-A receptors.

PubMed

Parsa, Hoda; Imani, Alireza; Faghihi, Mahdieh; Riahi, Esmail; Badavi, Mohammad; Shakoori, Abbas; Rastegar, Tayebeh; Aghajani, Marjan; Rajani, Sulail Fatima

2017-11-01

Central γ-aminobutyric acid (GABA) neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD) affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI), and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA) by assessing nitric oxide (NO) and oxidative stress. The CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist) administration. All animals underwent 30 min of coronary occlusion (ischemia), followed by 2 hr reperfusion (IR). The five experimental groups (n=12) included are as follows: IR: received saline; BIC+IR: received Bicuculline; MLP+IR: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD+IR: underwent ASD in an aquarium with multiple small platforms; and BIC+ASD+IR: received bicuculline prior to ASD. Bicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS) gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BIC+ASD+IR as compared to the ASD+IR group. Blockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production.

Trimucrin, an Arg-Gly-Asp containing disintegrin, attenuates myocardial ischemia-reperfusion injury in murine by inhibiting platelet function.

PubMed

Hung, Yu-Chun; Kuo, Yu-Ju; Huang, Shiang-Suo; Huang, Tur-Fu

2017-10-15

Trimucrin, a novel small-mass Arg-Gly-Asp (RGD)-containing disintegrin, has been demonstrated to possess anti-platelet and anti-inflammatory effect through blockade of platelet αIIbβ3 and phagocyte αvβ3 integrin. In this study, we found that the platelet-rich plasma prepared from trimucrin-treated rats platelet aggregation was diminished in response to adenosine diphosphate (ADP). We tried to determine whether trimucrin is cardioprotective in rats subjected to myocardial ischemia-reperfusion (I-R) injury. The left anterior descending coronary artery of anesthetized rats was subjected to 1h occlusion and 3h reperfusion. The animals received intravenous trimucrin or saline, and the severities of I-R-induced arrhythmia and infarction were compared. Trimucrin significantly reduced I-R-induced arrhythmias and reduced mortality, as well as infarct volume, troponin-I levels, creatine kinase, and lactate dehydrogenase activity in carotid blood compared with vehicle-treated animals during the same period. Trimucrin also improved cardiac function and survival rates after I-R injury. In addition, trimucrin concentration-dependently inhibited platelet adhesion on collagen- and fibrinogen-coated surfaces without affecting platelet counts. Trimucrin also significantly reduced neutrophil infiltration into heart tissues after I-R compared with controls. Furthermore, trimucrin treatment caused significant downregulation of Bax, Caspase-3 apoptotic proteins and upregulation of anti-apoptotic Bcl-2 protein. These results demonstrate that trimucrin exerts cardioprotective property against myocardial I-R injury mediated through antiplatele, anti-inflammatory, anti-apoptotic mechanism, as well as improvements in cardiac function. Copyright © 2017. Published by Elsevier B.V.

Mesenchymal stem cells derived from peripheral blood protects against ischemia.

PubMed

Ukai, Ryo; Honmou, Osamu; Harada, Kuniaki; Houkin, Kiyohiro; Hamada, Hirofumi; Kocsis, Jeffery D

2007-03-01

Intravenous delivery of mesenchymal stem cells (MSCs) prepared from bone marrow (BMSCs) reduces infarction volume and ameliorates functional deficits in a rat cerebral ischemia model. MSC-like multipotent precursor cells (PMSCs) have also been suggested to exist in peripheral blood. To test the hypothesis that treatment with PMSCs may have a therapeutic benefit in stroke, we compared the efficacy of systemic delivery of BMSCs and PMSCs. A permanent middle cerebral artery occlusion (MCAO) in rat was induced by intraluminal vascular occlusion with a microfilament. Rat BMSCs and PMSCs were prepared in culture and intravenously injected into the rats 6 h after MCAO. Lesion size was assessed at 6 h, and 1, 3, and 7 days using MR imaging and histology. The hemodynamic change of cerebral blood perfusion on stroke was assessed the same times using perfusion-weighted image (PWI). Functional outcome was assessed using the treadmill stress test. Both BMSCs and PMSCs treated groups had reduced lesion volume, improved regional cerebral blood flow, and functional improvement compared to the control group. The therapeutic benefits of both MSC-treated groups were similar. These data suggest that PMSCs derived from peripheral blood could be an important cell source of cell therapy for stroke.

Licorice Pretreatment Protects Against Brain Damage Induced by Middle Cerebral Artery Occlusion in Mice.

PubMed

Lim, Chiyeon; Lim, Sehyun; Lee, Byoungho; Kim, Buyeo; Cho, Suin

2018-05-01

Licorice is extracted from the roots of plants in the Glycyrrhiza genus, especially Glycyrrhiza uralensis in China and Korea. It has several pharmacological activities, including neuro-protective, anti-fungal, and anti-cariogenic effects. Ischemia/reperfusion-induced brain injury is a leading cause of adult disability and death; thus, the identification of anti-apoptotic, neuro-protective therapeutic agents is viewed as an attractive drug development strategy. Infarct volumes and the expression of several apoptosis-related proteins, including Bcl-xL, Bcl-2, caspase-8, and caspase-9, were evaluated by western blotting in the brains of mice subjected to middle cerebral artery occlusion (MCAO). Three consecutive days of oral pretreatment with the methanol extract of licorice (GRex) significantly reduced infarct volumes 24 h after MCAO. In addition, GRex effectively inhibited the activation of caspase-9 by upregulating protein expression of Bcl-xL and Bcl-2. The neuro-protective effect of licorice was due to its regulation of apoptosis-related proteins. These data suggest that licorice could be a potential candidate for the treatment of ischemia-induced brain damage.

The cardiac regenerative potential of myoblasts remains limited despite improving their survival via antioxidant treatment.

PubMed

Beckman, Sarah A; Sekiya, Naosumi; Chen, William C W; Mlakar, Logan; Tobita, Kimimassa; Huard, Johnny

2014-01-01

Since myoblasts have been limited by poor cell survival after cellular myoplasty, the major goal of the current study was to determine whether improving myoblast survival with an antioxidant could improve cardiac function after the transplantation of the myoblasts into an acute myocardial infarction. We previously demonstrated that early myogenic progenitors such as muscle-derived stem cells (MDSCs) exhibited superior cell survival and improved cardiac repair after transplantation into infarcted hearts compared to myoblasts, which we partially attributed to MDSC's higher antioxidant levels. To determine if antioxidant treatment could increase myoblast survival, subsequently improving cardiac function after myoblast transplantation into infarcted hearts. Myoblasts were pre-treated with the antioxidant N-acetylcysteine (NAC) or the glutathione depleter, diethyl maleate (DEM), and injected into infarcted murine hearts. Regenerative potential was monitored by cell survival and cardiac function. At early time points, hearts injected with NAC-treated myoblasts exhibited increased donor cell survival, greater cell proliferation, and decreased cellular apoptosis, compared to untreated myoblasts. NAC-treated myoblasts significantly improved cardiac contractility, reduced fibrosis, and increased vascular density compared to DEM-treated myoblasts, but compared to untreated myoblasts, no difference was noted. While early survival of myoblasts transplanted into infarcted hearts was augmented by NAC pre-treatment, cardiac function remained unchanged compared to non-treated myoblasts. Despite improving cell survival with NAC treated myoblast transplantation in a MI heart, cardiac function remained similar to untreated myoblasts. These results suggest that the reduced cardiac regenerative potential of myoblasts, when compared to MDSCs, is not only attributable to cell survival but is probably also related to the secretion of paracrine factors by the MDSCs.

The cardiac regenerative potential of myoblasts remains limited despite improving their survival via antioxidant treatment

PubMed Central

Beckman, Sarah A.; Sekiya, Naosumi; Chen, William C.W.; Mlakar, Logan; Tobita, Kimimassa; Huard, Johnny

2017-01-01

Introduction Since myoblasts have been limited by poor cell survival after cellular myoplasty, the major goal of the current study was to determine whether improving myoblast survival with an antioxidant could improve cardiac function after the transplantation of the myoblasts into an acute myocardial infarction. Background We previously demonstrated that early myogenic progenitors such as muscle-derived stem cells (MDSCs) exhibited superior cell survival and improved cardiac repair after transplantation into infarcted hearts compared to myoblasts, which we partially attributed to MDSC’s higher antioxidant levels. Aim To determine if antioxidant treatment could increase myoblast survival, subsequently improving cardiac function after myoblast transplantation into infarcted hearts. Materials and Methods Myoblasts were pre-treated with the antioxidant N-acetylcysteine (NAC) or the glutathione depleter, diethyl maleate (DEM), and injected into infarcted murine hearts. Regenerative potential was monitored by cell survival and cardiac function. Results At early time points, hearts injected with NAC-treated myoblasts exhibited increased donor cell survival, greater cell proliferation, and decreased cellular apoptosis, compared to untreated myoblasts. NAC-treated myoblasts significantly improved cardiac contractility, reduced fibrosis, and increased vascular density compared to DEM-treated myoblasts, but compared to untreated myoblasts, no difference was noted. Discussion While early survival of myoblasts transplanted into infarcted hearts was augmented by NAC pre-treatment, cardiac function remained unchanged compared to non-treated myoblasts. Conclusion Despite improving cell survival with NAC treated myoblast transplantation in a MI heart, cardiac function remained similar to untreated myoblasts. These results suggest that the reduced cardiac regenerative potential of myoblasts, when compared to MDSCs, is not only attributable to cell survival but is probably also related to the secretion of paracrine factors by the MDSCs. PMID:28989945

[System evaluation on Ginkgo Biloba extract in the treatment of acute cerebral infarction].

PubMed

Wang, Lin; Zhang, Tao; Bai, Kezhen

2015-10-01

To evaluate the effect and safety of Ginkgo Biloba extract on the treatment of acute cerebral infarction.
 The Database of Wanfang, China National Knowledge Infrastructure (CNKI) and VIPU were screened for literatures regarding Ginkgo Biloba extract in the treatment of acute cerebral infarction, including the clinical randomized controlled trials. Meta-analysis based on the Revman 4.2 system was performed.
 Compared with the control group, treatment with Ginkgo Biloba extract enhanced efficacy in the treatment of acute cerebral infarction (OR: 1.60-5.53), which displayed an improved neural function defect score [WMD -3.12 (95%CI: -3.96- -2.28)].
 Ginkgo Biloba extract is beneficial to the improvement of neurological function in patients with acute cerebral infarction and it is safe for patients.

Impact of gender on infarct size, ST-segment resolution, myocardial blush and clinical outcomes after primary stenting for acute myocardial infarction: Substudy from the EMERALD trial.

PubMed

Ng, Vivian G; Mori, Ken; Costa, Ricardo A; Kish, Mitra; Mehran, Roxana; Urata, Hidenori; Saku, Keijiro; Stone, Gregg W; Lansky, Alexandra J

2016-03-15

Women with AMI may have worse outcomes than men. However, it is unclear if this is related to differences in treatment, treatment effect or gender specific factors. We sought to determine whether primary percutaneous intervention (PCI) has a differential impact on infarct size, myocardial perfusion and ST segment resolution in men and women with acute myocardial infarction (AMI). A total of 501 AMI patients were prospectively enrolled in the EMERALD study and underwent PCI with or without distal protection. Post hoc gender subset analysis was performed. 501 patients (108 women, 393 men) with ST-segment elevation AMI presenting within 6h underwent primary (or rescue) PCI with stenting and a distal protection device. Women were older, had more hypertension, less prior AMI, smaller BSA, and smaller vessel size, but had similar rates of diabetes (30% versus 20.2%, p=0.87), LAD infarct, and time-to-reperfusion compared to men. Women more frequently had complete ST-resolution (>70%) at 30days (72.8% versus 59.8%, p=0.02), and smaller infarct size compared to males (12.2±19.6% versus 18.4±18.5%, p=0.006). At 6months, TLR (6.9% versus 5.2%) and MACE (11.4% versus 10.3%) were similar for women and men. Despite worse comorbidities, women with AMI treated with primary PCI with stenting showed similar early and midterm outcomes compared to men. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord stimulation improves left ventricular function in a porcine model of heart failure.

PubMed

Liao, Song-Yan; Liu, Yuan; Zuo, Mingliang; Zhang, Yuelin; Yue, Wensheng; Au, Ka-Wing; Lai, Wing-Hon; Wu, Yangsong; Shuto, Chika; Chen, Peter; Siu, Chung-Wah; Schwartz, Peter J; Tse, Hung-Fat

2015-12-01

Thoracic spinal cord stimulation (SCS) has been shown to improve left ventricular ejection fraction (LVEF) in heart failure (HF). Nevertheless, the optimal duration (intermittent vs. continuous) of stimulation and the mechanisms of action remain unclear. We performed chronic thoracic SCS at the level of T1-T3 (50 Hz, pulse width 0.2 ms) in 30 adult pigs with HF induced by myocardial infarction and rapid ventricular pacing for 4 weeks. All the animals were treated with daily oral metoprolol succinate (25 mg) plus ramipril (2.5 mg), and randomized to a control group (n = 10), intermittent SCS (4 h ×3, n = 10) or continuous SCS (24 h, n = 10) for 10 weeks. Serial measurements of LVEF and +dP/dt and serum levels of norepinephrine and B-type natriuretic peptide (BNP) were measured. After sacrifice, immunohistological studies of myocardial sympathetic and parasympathetic nerve sprouting and innervation were performed. Echocardiogram revealed a significant increase in LVEF and +dP/dt at 10 weeks in both the intermittent and continuous SCS group compared with controls (P < 0.05). In both SCS groups, there was diffuse sympathetic nerve sprouting over the infarct, peri-infarct, and normal regions compared with only the peri-infarct and infarct regions in the control group. In addition, sympathetic innervation at the peri-infarct and infarct regions was increased following SCS, but decreased in the control group. Myocardium norepinephrine spillover and serum BNP at 10 weeks was significantly decreased only in the continuous SCS group (P < 0.05). In a porcine model of HF, SCS induces significant remodelling of cardiac sympathetic innervation over the peri-infarct and infarct regions and is associated with improved LV function and reduced myocardial norepinephrine spillover. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies.

PubMed

Reilly, Muredach P; Li, Mingyao; He, Jing; Ferguson, Jane F; Stylianou, Ioannis M; Mehta, Nehal N; Burnett, Mary Susan; Devaney, Joseph M; Knouff, Christopher W; Thompson, John R; Horne, Benjamin D; Stewart, Alexandre F R; Assimes, Themistocles L; Wild, Philipp S; Allayee, Hooman; Nitschke, Patrick Linsel; Patel, Riyaz S; Martinelli, Nicola; Girelli, Domenico; Quyyumi, Arshed A; Anderson, Jeffrey L; Erdmann, Jeanette; Hall, Alistair S; Schunkert, Heribert; Quertermous, Thomas; Blankenberg, Stefan; Hazen, Stanley L; Roberts, Robert; Kathiresan, Sekar; Samani, Nilesh J; Epstein, Stephen E; Rader, Daniel J

2011-01-29

We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structural MRI correlates of apathy symptoms in older persons without dementia

PubMed Central

Grool, Anne M.; Geerlings, Mirjam I.; Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Jonsson, Palmi V.; Garcia, Melissa E.; Siggeirsdottir, Kristin; Harris, Tamara B.; Sigmundsson, Thordur; Gudnason, Vilmundur

2014-01-01

Objective: We aimed to investigate the relation between apathy symptoms and structural brain changes on MRI, including white matter lesions (WMLs) and atrophy, in a large cohort of older persons. Methods: Cross-sectional analyses are based on 4,354 persons without dementia (aged 76 ± 5 years) participating in the population-based Age, Gene/Environment Susceptibility–Reykjavik Study. Apathy symptoms were assessed with 3 items from the 15-item Geriatric Depression Scale. Brain volumes and total WML volume were estimated on 1.5-tesla MRI using an automated segmentation program; regional WML load was calculated using a semiquantitative scale. Regression analyses were adjusted for age, sex, education, intracranial volume, vascular risk factors, physical activity, brain infarcts, depressive symptoms, antidepressants, and cognitive status. Results: Compared to those with <2 apathy symptoms, participants with ≥2 apathy symptoms (49% of the cohort) had significantly smaller gray matter volumes (mean adjusted difference −3.6 mL, 95% confidence interval [CI] −6.2 to −1.0), particularly in the frontal and temporal lobes; smaller white matter volumes (mean adjusted difference −1.9 mL, 95% CI −3.6 to −0.3), mainly in the parietal lobe; and smaller thalamus volumes. They were also more likely to have WMLs in the frontal lobe (adjusted odds ratio = 1.08, 95% CI 0.9–1.3). Excluding participants with a depression diagnosis did not change the associations. Conclusions: In this older population without dementia, apathy symptoms are associated with a more diffuse loss of both gray and white matter volumes, independent of depression. PMID:24739783

Electromechanical wave imaging and electromechanical wave velocity estimation in a large animal model of myocardial infarction.

PubMed

Costet, Alexandre; Melki, Lea; Sayseng, Vincent; Hamid, Nadira; Nakanishi, Koki; Wan, Elaine; Hahn, Rebecca; Homma, Shunichi; Konofagou, Elisa

2017-11-29

Echocardiography is often used in the clinic for detection and characterization of myocardial infarction. Electromechanical wave imaging (EWI) is a non-invasive ultrasound-based imaging technique based on time-domain incremental motion and strain estimation that can evaluate changes in contractility in the heart. In this study, electromechanical activation is assessed in infarcted heart to determine whether EWI is capable of detecting and monitoring infarct formation. Additionally, methods for estimating electromechanical wave (EW) velocity are presented, and changes in the EW propagation velocity after infarct formation are studied. Five (n  =  5) adult mongrels were used in this study. Successful infarct formation was achieved in three animals by ligation of the left anterior descending (LAD) coronary artery. Dogs were survived for a few days after LAD ligation and monitored daily with EWI. At the end of the survival period, dogs were sacrificed and TTC (tetrazolium chloride) staining confirmed the formation and location of the infarct. In all three dogs, as soon as day 1 EWI was capable of detecting late-activated and non-activated regions, which grew over the next few days. On final day images, the extent of these regions corresponded to the location of infarct as confirmed by staining. EW velocities in border zones of infarct were significantly lower post-infarct formation when compared to baseline, whereas velocities in healthy tissues were not. These results indicate that EWI and EW velocity might help with the detection of infarcts and their border zones, which may be useful for characterizing arrhythmogenic substrate.

Electromechanical wave imaging and electromechanical wave velocity estimation in a large animal model of myocardial infarction

NASA Astrophysics Data System (ADS)

Costet, Alexandre; Melki, Lea; Sayseng, Vincent; Hamid, Nadira; Nakanishi, Koki; Wan, Elaine; Hahn, Rebecca; Homma, Shunichi; Konofagou, Elisa

2017-12-01

Echocardiography is often used in the clinic for detection and characterization of myocardial infarction. Electromechanical wave imaging (EWI) is a non-invasive ultrasound-based imaging technique based on time-domain incremental motion and strain estimation that can evaluate changes in contractility in the heart. In this study, electromechanical activation is assessed in infarcted heart to determine whether EWI is capable of detecting and monitoring infarct formation. Additionally, methods for estimating electromechanical wave (EW) velocity are presented, and changes in the EW propagation velocity after infarct formation are studied. Five (n  =  5) adult mongrels were used in this study. Successful infarct formation was achieved in three animals by ligation of the left anterior descending (LAD) coronary artery. Dogs were survived for a few days after LAD ligation and monitored daily with EWI. At the end of the survival period, dogs were sacrificed and TTC (tetrazolium chloride) staining confirmed the formation and location of the infarct. In all three dogs, as soon as day 1 EWI was capable of detecting late-activated and non-activated regions, which grew over the next few days. On final day images, the extent of these regions corresponded to the location of infarct as confirmed by staining. EW velocities in border zones of infarct were significantly lower post-infarct formation when compared to baseline, whereas velocities in healthy tissues were not. These results indicate that EWI and EW velocity might help with the detection of infarcts and their border zones, which may be useful for characterizing arrhythmogenic substrate.

The influence of myocardial substrate on ventricular fibrillation waveform: A swine model of acute and postmyocardial infarction

PubMed Central

Indik, Julia H.; Donnerstein, Richard L.; Hilwig, Ronald W.; Zuercher, Mathias; Feigelman, Justin; Kern, Karl B.; Berg, Marc D.; Berg, Robert A.

2009-01-01

Objective In cardiac arrest resulting from ventricular fibrillation, the ventricular fibrillation waveform may be a clue to its duration and predict the likelihood of shock success. However, ventricular fibrillation occurs in different myocardial substrates such as ischemia, heart failure, and structurally normal hearts. We hypothesized that ventricular fibrillation is altered by myocardial infarction and varies from the acute to postmyocardial infarction periods. Design An animal intervention study was conducted with comparison to a control group. Setting This study took place in a university animal laboratory. Subjects Study subjects included 37 swine. Interventions Myocardial infarction was induced by occlusion of the midleft anterior descending artery. Ventricular fibrillation was induced in control swine, acute myocardial infarction swine, and in postmyocardial infarction swine after a 2-wk recovery period. Measurements and Main Results Ventricular fibrillation was recorded in 11 swine with acute myocardial infarction, ten post-myocardial infarction, and 16 controls. Frequency (mean, median, dominant, and bandwidth) and amplitude-related content (slope, slope-amp [slope divided by amplitude], and amplitude–spectrum area) were analyzed. Frequencies at 5 mins of ventricular fibrillation were altered in both acute myocardial infarction (p < .001 for all frequency characteristics) and postmyocardial infarction swine (p = .015 for mean, .002 for median, .002 for dominant frequency, and <.001 for bandwidth). At 5 mins, median frequency was highest in controls, 10.9 ± .4 Hz; lowest in acute myocardial infarction, 8.4 ± .5 Hz; and intermediate in postmyocardial infarction, 9.7 ± .5 Hz (p < .001 for acute myocardial infarction and p = .002 for postmyocardial infarction compared with control). Slope and amplitude–spectrum area were similar among the three groups with a shallow decline after minute 2, whereas slope-amp remained significantly altered for acute myocardial infarction swine at 5 mins (p = .003). Conclusions Ventricular fibrillation frequencies depend on myocardial substrate and evolve from the acute through healing phases of myocardial infarction. Amplitude related measures, however, are similar among these groups. It is unknown how defibrillation may be affected by relying on the ventricular fibrillation waveform without considering myocardial substrate. PMID:18552696

Differences in symptoms, first medical contact and pre-hospital delay times between patients with ST- and non-ST-elevation myocardial infarction.

PubMed

Ängerud, Karin H; Sederholm Lawesson, Sofia; Isaksson, Rose-Marie; Thylén, Ingela; Swahn, Eva

2017-11-01

In ST-elevation myocardial infarction, time to reperfusion is crucial for the prognosis. Symptom presentation in myocardial infarction influences pre-hospital delay times but studies about differences in symptoms between patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction are sparse and inconclusive. The aim was to compare symptoms, first medical contact and pre-hospital delay times in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction. This multicentre, observational study included 694 myocardial infarction patients from five hospitals. The patients filled in a questionnaire about their pre-hospital experiences within 24 h of hospital admittance. Chest pain was the most common symptom in ST-elevation myocardial infarction and non-ST-elevation myocardial infarction (88.7 vs 87.0%, p=0.56). Patients with cold sweat (odds ratio 3.61, 95% confidence interval 2.29-5.70), jaw pain (odds ratio 2.41, 95% confidence interval 1.04-5.58), and nausea (odds ratio 1.70, 95% confidence interval 1.01-2.87) were more likely to present with ST-elevation myocardial infarction, whereas the opposite was true for symptoms that come and go (odds ratio 0.58, 95% confidence interval 0.38-0.90) or anxiety (odds ratio 0.52, 95% confidence interval 0.29-0.92). Use of emergency medical services was higher among patients admitted with ST-elevation myocardial infarction. The pre-hospital delay time from symptom onset to first medical contact was significantly longer in non-ST-elevation myocardial infarction (2:05 h vs 1:10 h, p=0.001). Patients with ST-elevation myocardial infarction differed from those with non-ST-elevation myocardial infarction regarding symptom presentation, ambulance utilisation and pre-hospital delay times. This knowledge is important to be aware of for all healthcare personnel and the general public especially in order to recognise symptoms suggestive of ST-elevation myocardial infarction and when to decide if there is a need for an ambulance.

Limited reliability of computed tomographic perfusion acute infarct volume measurements compared with diffusion-weighted imaging in anterior circulation stroke.

PubMed

Schaefer, Pamela W; Souza, Leticia; Kamalian, Shervin; Hirsch, Joshua A; Yoo, Albert J; Kamalian, Shahmir; Gonzalez, R Gilberto; Lev, Michael H

2015-02-01

Diffusion-weighted imaging (DWI) can reliably identify critically ischemic tissue shortly after stroke onset. We tested whether thresholded computed tomographic cerebral blood flow (CT-CBF) and CT-cerebral blood volume (CT-CBV) maps are sufficiently accurate to substitute for DWI for estimating the critically ischemic tissue volume. Ischemic volumes of 55 patients with acute anterior circulation stroke were assessed on DWI by visual segmentation and on CT-CBF and CT-CBV with segmentation using 15% and 30% thresholds, respectively. The contrast:noise ratios of ischemic regions on the DWI and CT perfusion (CTP) images were measured. Correlation and Bland-Altman analyses were used to assess the reliability of CTP. Mean contrast:noise ratios for DWI, CT-CBF, and CT-CBV were 4.3, 0.9, and 0.4, respectively. CTP and DWI lesion volumes were highly correlated (R(2)=0.87 for CT-CBF; R(2)=0.83 for CT-CBV; P<0.001). Bland-Altman analyses revealed little systemic bias (-2.6 mL) but high measurement variability (95% confidence interval, ±56.7 mL) between mean CT-CBF and DWI lesion volumes, and systemic bias (-26 mL) and high measurement variability (95% confidence interval, ±64.0 mL) between mean CT-CBV and DWI lesion volumes. A simulated treatment study demonstrated that using CTP-CBF instead of DWI for detecting a statistically significant effect would require at least twice as many patients. The poor contrast:noise ratios of CT-CBV and CT-CBF compared with those of DWI result in large measurement error, making it problematic to substitute CTP for DWI in selecting individual acute stroke patients for treatment. CTP could be used for treatment studies of patient groups, but the number of patients needed to identify a significant effect is much higher than the number needed if DWI is used. © 2014 American Heart Association, Inc.

Diet-Induced Ketosis Protects Against Focal Cerebral Ischemia in Mouse.

PubMed

Xu, Kui; Ye, Lena; Sharma, Katyayini; Jin, Yongming; Harrison, Matthew M; Caldwell, Tylor; Berthiaume, Jessica M; Luo, Yu; LaManna, Joseph C; Puchowicz, Michelle A

2017-01-01

Over the past decade we have consistently shown that ketosis is neuroprotective against ischemic insults in rats. We reported that diet-induced ketotic rats had a significant reduction in infarct volume when subjected to middle cerebral artery occlusion (MCAO), and improved survival and recovery after cardiac arrest and resuscitation. The neuroprotective mechanisms of ketosis (via ketogenic diet; KG) include (i) ketones are alternate energy substrates that can restore energy balance when glucose metabolism is deficient and (ii) ketones modulate cell-signalling pathways that are cytoprotective. We investigated the effects of diet-induced ketosis following transient focal cerebral ischemia in mice. The correlation between levels of ketosis and hypoxic inducible factor-1alpha (HIF-1α), AKT (also known as protein kinase B or PKB) and 5' AMP-activated protein kinase (AMPK) were determined. Mice were fed with KG diet or standard lab-chow (STD) diet for 4 weeks. For the MCAO group, mice underwent 60 min of MCAO and total brain infarct volumes were evaluated 48 h after reperfusion. In a separate group of mice, brain tissue metabolites, levels of HIF-1α, phosphorylated AKT (pAKT), and AMPK were measured. After feeding a KG diet, levels of blood ketone bodies (beta-hydroxyburyrate, BHB) were increased. There was a proportional decrease in infarct volumes with increased blood BHB levels (KG vs STD; 4.2 ± 0.6 vs 7.8 ± 2.2 mm 3 , mean ± SEM). A positive correlation was also observed with HIF-1α and pAKT relative to blood BHB levels. Our results showed that chronic ketosis can be induced in mice by KG diet and was neuroprotective against focal cerebral ischemia in a concentration dependent manner. Potential mechanisms include upregulation of cytoprotective pathways such as those associated with HIF-1α, pAKT and AMPK.

Neuroprotection by triptolide against cerebral ischemia/reperfusion injury through the inhibition of NF-κB/PUMA signal in rats.

PubMed

Zhang, Bin; Song, Cunfeng; Feng, Bo; Fan, Weibing

2016-01-01

Triptolide, an active compound extracted from the Chinese herb thunder god vine (Tripterygium wilfordii Hook F.), has potent antitumor activity. Recently, triptolide was found to have protective effects against acute cerebral ischemia/reperfusion (I/R) injury through inhibition of cell apoptosis. However, the regulatory mechanism of the effect remains unclear. We hypothesize that the regulatory mechanisms of triptolide are mediated by nuclear factor κB (NF-κB) and p53-upregulated-modulator-of-apoptosis signal inhibition. To verify this hypothesis, we occluded the middle cerebral artery in male rats to establish focal cerebral I/R model. The rats received triptolide or vehicle at the onset of reperfusion following middle cerebral artery occlusion. At 24 hours after reperfusion, neurological deficits, infarct volume, and cell apoptosis were evaluated. The expression levels of NF-κBp65, PUMA, and caspase-3 were determined by Western blot. Real-time polymerase chain reaction was used to determine the levels of NF-κBp65 mRNA, PUMA mRNA, and caspase-3 mRNA. NF-κB activity was determined by electrophoretic mobility shift assay. Apoptotic cells were detected using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. In I/R group, neurological deficit scores, cerebral infarct volume, expression of NF-κBp65, PUMA, caspase-3, NF-κB activity, and TUNEL-positive cells were found to be increased at 24 hours after I/R injury. The I/R/triptolide rats showed significantly better neurological deficit scores, decreased neural apoptosis, and reduced cerebral infarct volume. In addition, the expression of NF-κBp65, PUMA, caspase-3, and NF-κB activity was suppressed in the I/R/triptolide rats. These results indicate that the neuroprotective effects of triptolide during acute cerebral I/R injury are possibly related to the inhibition of apoptosis through suppression of NF-κB/PUMA signaling pathway.

Plasma tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9: novel indicators of left ventricular remodelling and prognosis after acute myocardial infarction.

PubMed

Kelly, Dominic; Khan, Sohail Q; Thompson, Matt; Cockerill, Gillian; Ng, Leong L; Samani, Nilesh; Squire, Iain B

2008-09-01

Matrix metalloproteinase (MMP) activity is central to the development of left ventricular (LV) remodelling and dysfunction after acute myocardial infarction (AMI). We assessed the relationships with LV structure and function and outcome, of tissue inhibitors of metalloproteinase-1 (TIMP-1) and MMP-9, and compared with N-terminal pro-B-type natriuretic peptide (NTproBNP). We studied 404 patients with AMI. Primary outcome measures were the associations of TIMP-1, MMP-9, and NTproBNP with death or heart failure, and with LV dimensions, function and remodelling (ΔLVEDV, change in LV end-diastolic volume between discharge and follow-up). Cut-off concentrations for prediction of death or heart failure were identified from receiver operator characteristic (ROC) curves. In multivariable analysis, TIMP-1 and NTproBNP had predictive value for LV ejection fraction pre-discharge (TIMP-1 P = 0.023; N-BNP P = 0.007) and at follow-up (TIMP-1 P = 0.001; N-BNP P = 0.003). MMP-9, TIMP-1, and NTproBNP correlated directly with LV volumes. MMP-9 (P = 0.005) and TIMP-1 (P = 0.036), but not NTproBNP, correlated with ΔLVEDV. For the combined endpoint of death or heart failure the area under the ROC curve was 0.640 for MMP-9, 0.799 for NTproBNP and 0.811 for TIMP-1. Patients with TIMP-1 > 135 ng/mL (P < 0.001) or NTproBNP >1472 fmol/mL (P < 0.001) had increased risk of endpoint. Consideration of both NTproBNP and TIMP-1 further improved risk stratification. TIMP-1 and MMP-9 correlate with echocardiographic parameters of LV dysfunction and remodelling after AMI and may identify patients at risk of subsequent LV remodelling and adverse prognosis.

Functional Trajectories, Cognition, and Subclinical Cerebrovascular Disease.

PubMed

Dhamoon, Mandip S; Cheung, Ying-Kuen; Gutierrez, Jose; Moon, Yeseon P; Sacco, Ralph L; Elkind, Mitchell S V; Wright, Clinton B

2018-03-01

Cognition and education influence functional trajectories, but whether associations differ with subclinical brain infarcts (SBI) or white matter hyperintensity volume (WMHV) is unknown. We hypothesized that SBI and WMHV moderated relationships between cognitive performance and education and functional trajectories. A total of 1290 stroke-free individuals underwent brain magnetic resonance imaging and were followed for 7.3 years (mean) with annual functional assessments with the Barthel index (range, 0-100). Magnetic resonance imaging measurements included pathology-informed SBI (PI-SBI) and WMHV (% total cranial volume). Generalized estimating equation models tested associations between magnetic resonance imaging variables and baseline Barthel index and change in Barthel index, adjusting for demographic, vascular, cognitive, and social risk factors, and stroke and myocardial infarction during follow-up. We tested interactions among education level, baseline cognitive performance (Mini-Mental State score), and functional trajectories and ran models stratified by levels of magnetic resonance imaging variables. Mean age was 70.6 (SD, 9.0) years; 19% had PI-SBI, and mean WMHV was 0.68%. Education did not modify associations between cognition and functional trajectories. PI-SBI modified associations between cognition and functional trajectories ( P =0.04) with a significant protective effect of better cognition on functional decline seen only in those without PI-SBI. There was no significant interaction for WMHV ( P =0.8). PI-SBI, and greater WMHV, were associated with 2- to 3-fold steeper functional decline, holding cognition constant. PI-SBI moderated the association between cognition and functional trajectories, with 3-fold greater decline among those with PI-SBI (compared with no PI-SBI) and normal baseline cognition. This highlights the strong and independent association between subclinical markers and patient-centered trajectories over time. © 2018 American Heart Association, Inc.

Sulforaphane improves outcomes and slows cerebral ischemic/reperfusion injury via inhibition of NLRP3 inflammasome activation in rats.

PubMed

Yu, Chang; He, Qi; Zheng, Jing; Li, Ling Yu; Hou, Yang Hao; Song, Fang Zhou

2017-04-01

Ischemia/reperfusion (I/R) injury has been correlated with systemic inflammatory response. In addition, NLRP3 has been suggested as a cause in many inflammatory processes. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli and cabbage. While recent studies have demonstrated that Sulforaphane has protective effects against cerebral ischemia/reperfusion injury, little is known about how those protective effects work. In this study, we focus our investigation on the role and process of Sulforaphane in the inhibition of NLRP3 inflammasome activation, as well as its effect on brain ischemia/reperfusion injury. Adult male Sprague-Dawley rats were injected with Sulforaphane (5 or 10mg/kg) intraperitoneally at the beginning of reperfusion, after a 60min period of occlusion. A neurological score and infarct volume were assessed at 24h after the administration of Sulforaphane. Myeloperoxidase (MPO) activity was measured at 24h to assess neutrophil infiltration in brain tissue. ELISA, RT-PCR and Western blot analyses were used to measure any inflammatory reaction. Sulforaphane treatment significantly reduced infarct volume and improved neurological scores when compared to a vehicle-treated group. Neutrophil infiltration was significantly higher in the vehicle-treated group than in the Sulforaphane treatment group. Sulforaphane treatment inhibits NLRP3 inflammasome activation and the downregulation of cleaved caspase-1, while reducing IL-1β and IL-18 expression. The inhibition of inflammatory response with Sulforaphane treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by Sulforaphane inhibited NLRP3 inflammasome activation caused by the downregulation of NLRP3, the induction of cleaved caspase-1, and thus the reduction of IL-1β and IL-18. Copyright © 2017 Elsevier B.V. All rights reserved.

Physician awareness of decompressive hemicraniectomy for malignant middle cerebral artery infarction in Saudi Arabia and the Gulf countries.

PubMed

Al-Jehani, Hosam M; Alsharydah, Abdulaziz; Rammal, Seba A; Baeesa, Saleh S; Mekhlafi, Mohammad

2018-04-01

To explore the perspective on Decompressive craniectomy (DH) of each of these specialties to establish common grounds for improved clinical practice. An electronic survey was distributed via email and social media groups to members of these specialties in Kingdom of Saudi Arabia and the Gulf countries. Local practices, common triggers for referral for DH, perceived outcomes of these procedures, individual impression of what constitutes good clinical outcomes were explored. There are 89 physicians participated: 41 (46.1%) neurologists, 34 (38.2%) neurosurgeons, and 14 (15.7%) intensivests. Participants are mostly practicing in intermediate volume centers or high volume centers. Half of the neurosurgeons preferred to be consulted immediately on candidates with large middle cerebral artery (MCA) strokes. The most important referral trigger for DH was clinical changes. The modified Rankin Scale (mRS) cutoff for good clinical outcome was 3 for 73.6% of respondents. There was agreement that DH only improves survival (64.4%). A third of the neurologists considered it to improve functional outcome compared to 15.4% of intensivests and 14.8% of neurosurgeons. There was agreement (66.7%) that patients older than 60 years with involvement of more than one territory should be excluded from DH. Only 7.7% of neurosurgeons excluded patients with dominant hemispheric strokes. Our physicians` views are variable in what`s called acceptable outcome, and further studies are needed to to test the characteristics that helps in decision making such as hemisphere dominancy, time onset of stroke and vital radiological signs. This is seen despite the literature being full of data that supports the DC over medical management in malignant MCA infarction. Better multidisciplinary education initiatives are needed to unify the understanding and help improve the practices in this challenging subset of patients.

Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by Promoting M2 Macrophage Polarization.

PubMed

Chu, Hannah X; Broughton, Brad R S; Kim, Hyun Ah; Lee, Seyoung; Drummond, Grant R; Sobey, Christopher G

2015-07-01

Ly6C(hi) monocytes are generally thought to exert a proinflammatory role in acute tissue injury, although their impact after injuries to the central nervous system is poorly defined. CC chemokine receptor 2 is expressed on Ly6C(hi) monocytes and plays an essential role in their extravasation and transmigration into the brain after cerebral ischemia. We used a selective CC chemokine receptor 2 antagonist, INCB3344, to assess the effect of Ly6C(hi) monocytes recruited into the brain early after ischemic stroke. Male C57Bl/6J mice underwent occlusion of the middle cerebral artery for 1 hour followed by 23 hours of reperfusion. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (10, 30 or 100 mg/kg IP) 1 hour before ischemia and at 2 and 6 hours after ischemia. At 24 hours, we assessed functional outcomes, infarct volume, and quantified the immune cells in blood and brain by flow cytometry or immunofluorescence. Gene expression of selected inflammatory markers was assessed by quantitative polymerase chain reaction. Ly6C(hi) monocytes were increased 3-fold in the blood and 10-fold in the brain after stroke, and these increases were selectively prevented by INCB3344 in a dose-dependent manner. Mice treated with INCB3344 exhibited markedly worse functional outcomes and larger infarct volumes, in association with reduced M2 polarization and increased peroxynitrite production in macrophages, compared with vehicle-treated mice. Our data suggest that Ly6C(hi) monocytes exert an acute protective effect after ischemic stroke to limit brain injury and functional deficit that involves promotion of M2 macrophage polarization. © 2015 American Heart Association, Inc.

The Synergistic Neuroprotective Effects of Combined Rosuvastatin and Resveratrol Pretreatment against Cerebral Ischemia/Reperfusion Injury.

PubMed

Liu, Ying; Yang, HongNa; Jia, GuoYong; Li, Lan; Chen, Hui; Bi, JianZhong; Wang, CuiLan

2018-06-01

It is well accepted that both rosuvastatin and resveratrol exert neuroprotective effects on cerebral ischemia/reperfusion injury through some common pathways. Resveratrol has also been demonstrated to protect against cerebral ischemia/reperfusion injury through enhancing autophagy. Thus, we hypothesized that combined rosuvastatin and resveratrol pretreatment had synergistic effects on cerebral ischemia/reperfusion injury. Adult male Sprague Dawley rats receiving middle cerebral artery occlusion surgery as animal model of cerebral ischemia/reperfusion injury were randomly assigned to 4 groups: control, resveratrol alone pretreatment, rosuvastatin alone pretreatment, and combined rosuvastatin and resveratrol pretreatment. Rosuvastatin (10 mg/kg) or resveratrol (50 mg/kg) was administrated once a day for 7 days before cerebral ischemia onset. We found that combined rosuvastatin and resveratrol pretreatment not only significantly decreased the neurologic defective score, cerebral infarct volume, the levels of caspase-3, and Interleukin-1β (IL-1β) but also significantly increased the ratios of Bcl-2/Bax and LC3II/LC3I, as well as the level of Becline-1, compared with resveratrol alone or rosuvastatin alone pretreatment group. Rosuvastatin alone pretreatment significantly increased the ratio of LC3II/LC3I and the level of Beclin-1. However, there were no significant differences in the neurologic defective score, cerebral infarct volume, the levels of caspase-3, IL-1β, and Beclin-1, and the ratios of Bcl-2/Bax and LC3II/LC3I between resveratrol pretreatment group and rosuvastatin pretreatment group. Synergistically enhanced antiapoptosis, anti-inflammation, and autophagy activation might be responsible for the synergistic neuroprotective effects of combining rosuvastatin with resveratrol on cerebral ischemia/reperfusion injury. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Regulatory CD8+CD122+ T-cells predominate in CNS after treatment of experimental stroke in male mice with IL-10-secreting B-cells

PubMed Central

Lapato, Andrew; Vandenbark, Arthur A.; Murphy, Stephanie J.; Saugstad, Julie A.; Offner, Halina

2014-01-01

Clinical stroke induces inflammatory processes leading to cerebral and splenic injury and profound peripheral immunosuppression. IL-10 expression is elevated during major CNS diseases and limits inflammation in the brain. Recent evidence demonstrated that transfer of IL-10+ B-cells reduced infarct volume in male C57BL/6J (wild-type, WT) recipient mice when given 24 h prior to or 4 h after middle cerebral artery occlusion (MCAO). The purpose of this study was to determine if passively transferred IL-10+ B-cells can exert therapeutic and immunoregulatory effects when injected 24 hours after MCAO induction in B-cell-sufficient male WT mice. The results demonstrated that IL-10+ B-cell treated mice had significantly reduced infarct volumes in the ipsilateral cortex and hemisphere and improved neurological deficits vs. Vehicle-treated control mice after 60 min occlusion and 96 h of reperfusion. The MCAO-protected B-cell recipient mice had less splenic atrophy and reduced numbers of activated, inflammatory T-cells, decreased infiltration of T-cells and a less inflammatory milieu in the ischemic hemispheres compared with Vehicle-treated control mice. These immunoregulatory changes occurred in concert with the predominant appearance of IL-10-secreting CD8+CD122+ Treg cells in both the spleen and the MCAO-affected brain hemisphere. This study for the first time demonstrates a major neuroprotective role for IL-10+ B-cells in treating MCAO in male WT mice at a time point well beyond the ~4 h tPA treatment window, leading to the generation of a dominant IL-10+CD8+CD122+ Treg population associated with spleen preservation and reduced CNS inflammation. PMID:25537181

Nox2 Knockout Delays Infarct Progression and Increases Vascular Recovery through Angiogenesis in Mice following Ischaemic Stroke with Reperfusion

PubMed Central

McCann, Sarah K.; Dusting, Gregory J.; Roulston, Carli L.

2014-01-01

Evidence suggests the NADPH oxidases contribute to ischaemic stroke injury and Nox2 is the most widely studied subtype in the context of stroke. There is still conjecture however regarding the benefits of inhibiting Nox2 to improve stroke outcome. The current study aimed to examine the temporal effects of genetic Nox2 deletion on neuronal loss after ischaemic stroke using knockout (KO) mice with 6, 24 and 72 hour recovery. Transient cerebral ischaemia was induced via intraluminal filament occlusion and resulted in reduced infarct volumes in Nox2 KO mice at 24 h post-stroke compared to wild-type controls. No protection was evident at either 6 h or 72 h post-stroke, with both genotypes exhibiting similar volumes of damage. Reactive oxygen species were detected using dihydroethidium and were co-localised with neurons and microglia in both genotypes using immunofluorescent double-labelling. The effect of Nox2 deletion on vascular damage and recovery was also examined 24 h and 72 h post-stroke using an antibody against laminin. Blood vessel density was decreased in the ischaemic core of both genotypes 24 h post-stroke and returned to pre-stroke levels only in Nox2 KO mice by 72 h. Overall, these results are the first to show that genetic Nox2 deletion merely delays the progression of neuronal loss after stroke but does not prevent it. Additionally, we show for the first time that Nox2 deletion increases re-vascularisation of the damaged brain by 72 h, which may be important in promoting endogenous brain repair mechanisms that rely on re-vascularisation. PMID:25375101

Reported Prestroke Physical Activity Is Associated with Vascular Endothelial Growth Factor Expression and Good Outcomes after Stroke.

PubMed

López-Cancio, Elena; Ricciardi, Ana Clara; Sobrino, Tomás; Cortés, Jordi; de la Ossa, Natalia Pérez; Millán, Mónica; Hernández-Pérez, María; Gomis, Meritxell; Dorado, Laura; Muñoz-Narbona, Lucía; Campos, Francisco; Arenillas, Juan F; Dávalos, Antoni

2017-02-01

Physical activity (PhA) prior to stroke has been associated with good outcomes after the ischemic insult, but there is scarce data on the involved molecular mechanisms. We studied consecutive acute ischemic stroke patients admitted to a single tertiary stroke center. Prestroke PhA was evaluated with the International Physical Activity Questionnaire (metabolic equivalent of minutes/week). We studied several circulating angiogenic and neurogenic factors at different time points: vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and brain-derived neurotrophic factor (BDNF) at admission, day 7, and at 3 months. We considered good functional outcome at 3 months (modified Rankin scale  ≤ 2) as primary end point, and final infarct volume as secondary outcome. We studied 83 patients with at least 2 time point serum determinations (mean age 69.6 years, median National Institutes of Health Stroke Scale 17 at admission). Patients more physically active before stroke had a significantly higher increment of serum VEGF on the seventh day when compared to less active patients. This increment was an independent predictor of good functional outcome at 3 months and was associated with smaller infarct volume in multivariate analyses adjusted for relevant covariates. We did not find independent associations of G-CSF or BDNF levels neither with level of prestroke PhA nor with stroke outcomes. Although there are probably more molecular mechanisms by which PhA exerts its beneficial effects in stroke outcomes, our observation regarding the potential role of VEGF is plausible and in line with previous experimental studies. Further research in this field is needed. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Diagnostic usefulness of the oedema-infarct ratio to differentiate acute from chronic myocardial damage using magnetic resonance imaging.

PubMed

Yamada, Kiyoyasu; Isobe, Satoshi; Suzuki, Susumu; Kinoshita, Kousuke; Yokouchi, Kazuhiko; Iwata, Hirokazu; Ohshima, Satoru; Hirai, Makoto; Sawada, Ken; Murohara, Toyoaki

2012-04-01

To differentiate acute from chronic damage to the myocardium in patients with myocardial infarction (MI) using DE and T2w MR. Short-axis T2w and DE MR images were acquired twice after the onset of MI in 36 patients who successfully underwent emergency coronary revascularisation. The areas of infarct and oedema were measured. The oedema-infarct ratio (O/I) of the left ventricular area was calculated by dividing the oedema by the infarct area. The oedema size on T2w MR was significantly larger than the infarct size on DE MR in the acute phase. Both the oedema size on T2w MR and the infarct size on DE MR in the acute phase were significantly larger than those in the chronic phase. The O/I was significantly greater in the acute phase compared with that in the chronic phase (P < 0.05). An analysis of relative cumulative frequency distributions revealed an O/I of 1.4 as a cut-off value for differentiating acute from chronic myocardial damage with the sensitivity, specificity, and accuracy of 85.1%, 82.7% and 83.9%, respectively. The oedema-infarct ratio may be a useful index in differentiating acute from chronic myocardial damage in patients with MI. MR can differentiate reversible from irreversible myocardial damage after myocardial infarction. MR is a useful modality to noninvasively differentiate the infarct stages. The O/I is an important index to decide therapeutic strategies.

Clinical and imaging features in different inner border-zone infarct patterns.

PubMed

Wang, Yujie; Wang, Jian

2015-03-01

The clinical and imaging features of different inner border-zone infarct patterns, corona radiata (CR) and centrum semiovale (CSO), is not quiet clear. Both are mostly reported together in previous studies. We intended to observe their clinical and imaging features. We observed 83 patients-47 cases with CR infarct lesion pattern and 36 cases with CSO. The lesion patterns were determined by diffusion-weighted imaging. Basic, clinical and radiologic features were compared between the patients with CR and CSO infarct lesion patterns. There was no significant difference between CR and CSO infarct patterns in terms of risk factors. However, patients with CR infarct had a higher initial National Institutes of Health Stroke Scale (NIHSS) score at admission (5.2 ± 2.3) than with CSO (3.9 ± 2.0, p = 0.009). Early clinical deterioration (OR, 2.42; 95% CI, 1.12-5.21; p = 0.024) and middle cerebral artery (MCA) stenosis (OR, 10.31; 95% CI, 3.30-32.19; p < 0.0001) were independently associated with the CR infarct lesion pattern. Partial infarct lesion shape (OR, 5.95; 95% CI, 1.40-25.33; p = 0.016) and internal carotid artery (ICA) stenosis (OR, 5.28; 95% CI, 1.92-14.51; p = 0.001) were independently correlated with the CSO infarct lesion pattern. Although CR and CSO infarct patterns might share common etiology and mechanisms, their clinical and imaging features are different.

Image-based reconstruction of three-dimensional myocardial infarct geometry for patient-specific modeling of cardiac electrophysiology

PubMed Central

Ukwatta, Eranga; Arevalo, Hermenegild; Rajchl, Martin; White, James; Pashakhanloo, Farhad; Prakosa, Adityo; Herzka, Daniel A.; McVeigh, Elliot; Lardo, Albert C.; Trayanova, Natalia A.; Vadakkumpadan, Fijoy

2015-01-01

Purpose: Accurate three-dimensional (3D) reconstruction of myocardial infarct geometry is crucial to patient-specific modeling of the heart aimed at providing therapeutic guidance in ischemic cardiomyopathy. However, myocardial infarct imaging is clinically performed using two-dimensional (2D) late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) techniques, and a method to build accurate 3D infarct reconstructions from the 2D LGE-CMR images has been lacking. The purpose of this study was to address this need. Methods: The authors developed a novel methodology to reconstruct 3D infarct geometry from segmented low-resolution (Lo-res) clinical LGE-CMR images. Their methodology employed the so-called logarithm of odds (LogOdds) function to implicitly represent the shape of the infarct in segmented image slices as LogOdds maps. These 2D maps were then interpolated into a 3D image, and the result transformed via the inverse of LogOdds to a binary image representing the 3D infarct geometry. To assess the efficacy of this method, the authors utilized 39 high-resolution (Hi-res) LGE-CMR images, including 36 in vivo acquisitions of human subjects with prior myocardial infarction and 3 ex vivo scans of canine hearts following coronary ligation to induce infarction. The infarct was manually segmented by trained experts in each slice of the Hi-res images, and the segmented data were downsampled to typical clinical resolution. The proposed method was then used to reconstruct 3D infarct geometry from the downsampled images, and the resulting reconstructions were compared with the manually segmented data. The method was extensively evaluated using metrics based on geometry as well as results of electrophysiological simulations of cardiac sinus rhythm and ventricular tachycardia in individual hearts. Several alternative reconstruction techniques were also implemented and compared with the proposed method. Results: The accuracy of the LogOdds method in reconstructing 3D infarct geometry, as measured by the Dice similarity coefficient, was 82.10% ± 6.58%, a significantly higher value than those of the alternative reconstruction methods. Among outcomes of electrophysiological simulations with infarct reconstructions generated by various methods, the simulation results corresponding to the LogOdds method showed the smallest deviation from those corresponding to the manual reconstructions, as measured by metrics based on both activation maps and pseudo-ECGs. Conclusions: The authors have developed a novel method for reconstructing 3D infarct geometry from segmented slices of Lo-res clinical 2D LGE-CMR images. This method outperformed alternative approaches in reproducing expert manual 3D reconstructions and in electrophysiological simulations. PMID:26233186

Image-based reconstruction of three-dimensional myocardial infarct geometry for patient-specific modeling of cardiac electrophysiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ukwatta, Eranga, E-mail: eukwatt1@jhu.edu; Arevalo, Hermenegild; Pashakhanloo, Farhad

Purpose: Accurate three-dimensional (3D) reconstruction of myocardial infarct geometry is crucial to patient-specific modeling of the heart aimed at providing therapeutic guidance in ischemic cardiomyopathy. However, myocardial infarct imaging is clinically performed using two-dimensional (2D) late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) techniques, and a method to build accurate 3D infarct reconstructions from the 2D LGE-CMR images has been lacking. The purpose of this study was to address this need. Methods: The authors developed a novel methodology to reconstruct 3D infarct geometry from segmented low-resolution (Lo-res) clinical LGE-CMR images. Their methodology employed the so-called logarithm of odds (LogOdds) function to implicitlymore » represent the shape of the infarct in segmented image slices as LogOdds maps. These 2D maps were then interpolated into a 3D image, and the result transformed via the inverse of LogOdds to a binary image representing the 3D infarct geometry. To assess the efficacy of this method, the authors utilized 39 high-resolution (Hi-res) LGE-CMR images, including 36 in vivo acquisitions of human subjects with prior myocardial infarction and 3 ex vivo scans of canine hearts following coronary ligation to induce infarction. The infarct was manually segmented by trained experts in each slice of the Hi-res images, and the segmented data were downsampled to typical clinical resolution. The proposed method was then used to reconstruct 3D infarct geometry from the downsampled images, and the resulting reconstructions were compared with the manually segmented data. The method was extensively evaluated using metrics based on geometry as well as results of electrophysiological simulations of cardiac sinus rhythm and ventricular tachycardia in individual hearts. Several alternative reconstruction techniques were also implemented and compared with the proposed method. Results: The accuracy of the LogOdds method in reconstructing 3D infarct geometry, as measured by the Dice similarity coefficient, was 82.10% ± 6.58%, a significantly higher value than those of the alternative reconstruction methods. Among outcomes of electrophysiological simulations with infarct reconstructions generated by various methods, the simulation results corresponding to the LogOdds method showed the smallest deviation from those corresponding to the manual reconstructions, as measured by metrics based on both activation maps and pseudo-ECGs. Conclusions: The authors have developed a novel method for reconstructing 3D infarct geometry from segmented slices of Lo-res clinical 2D LGE-CMR images. This method outperformed alternative approaches in reproducing expert manual 3D reconstructions and in electrophysiological simulations.« less

Low dose CT perfusion in acute ischemic stroke.

PubMed

Murphy, Amanda; So, Aaron; Lee, Ting-Yim; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I

2014-12-01

The purpose of this investigation is to determine if CT perfusion (CTP) measurements at low doses (LD = 20 or 50 mAs) are similar to those obtained at regular doses (RD = 100 mAs), with and without the addition of adaptive statistical iterative reconstruction (ASIR). A single-center, prospective study was performed in patients with acute ischemic stroke (n = 37; 54% male; age = 74 ± 15 years). Two CTP scans were performed on each subject: one at 100 mAs (RD) and one at either 50 or 20 mAs (LD). CTP parameters were compared between the RD and LD scans in regions of ischemia, infarction, and normal tissue. Differences were determined using a within-subjects ANOVA (p < 0.05) followed by a paired t test post hoc analysis (p < 0.01). At 50 mAs, there was no significant difference between cerebral blood flow (CBF), cerebral blood volume (CBV), or time to maximum enhancement (Tmax) values for the RD and LD scans in the ischemic, infarcted, or normal contralateral regions (p < 0.05). At 20 mAs, there were significant differences between the RD and LD scans for all parameters in the ischemic and normal tissue regions (p > 0.05). CTP-derived CBF and CBV are not different at 50 mAs compared to 100 mAs, even without the addition of ASIR. Current CTP protocols can be modified to reduce the effective dose by 50 % without altering CTP measurements.

Relations of arterial stiffness and endothelial function to brain aging in the community.

PubMed

Tsao, Connie W; Seshadri, Sudha; Beiser, Alexa S; Westwood, Andrew J; Decarli, Charles; Au, Rhoda; Himali, Jayandra J; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Larson, Martin G; Benjamin, Emelia J; Wolf, Philip A; Vasan, Ramachandran S; Mitchell, Gary F

2013-09-10

To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging. Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively). Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05). Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.

Right ventricular involvement in patients with inferior myocardial infarction, correlation of electrocardiographic findings with echocardiography data.

PubMed

Javed, Sumbul; Rajani, Ali Raza; Govindaswamy, Pushparani; Radaideh, Ghazi Ahmed; Abubaraka, Harb Ahmed; Qureshi, Tariq Ilyas; Arshad, Hassaan Bin

2017-03-01

To determine the right ventricular involvement in patients with inferior myocardial infarction by echocardiography in relation to electrocardiographic findings. This observational, prospective study was conducted at Rashid Hospital, Dubai, the United Arab Emirates, from January to September 2013, and comprised patients with inferior myocardial infarction. All patients aged above 18 years were included. Right ventricular myocardial infarction was defined by the electrocardiographic criteria of > 1mV ST elevation in V4R-V5R leads. RV infarction was assessed on echocardiography by fractional area change, tricuspid annular plane systolic excursion and tricuspid annular systolic velocity by tissue Doppler imaging. SPSS 21 was used for data analysis. Of the 73 patients, there were 68(93%) men and 5(7%) women. The three modalities used to assess the right ventricular infarction showed right ventricular involvement in 36(49.3%) cases by fractional area change, 28(38.4%) cases by tricuspid annular plane systolic excursion and 31(42.5%) cases by tissue Doppler imaging in patients with inferior myocardial infarction. Tissue Doppler imaging and right ventricular function showed low degree of negative correlation (p=0.16) while the correlation between tricuspid annular plane systolic excursion and right ventricular function showed significant positive correlation (p<0.0001). Assessment of right ventricular infarction by echocardiography helped to diagnose right ventricular infarction in greater number of cases compared to surface electrocardiogram.

Self-rated function, self-rated health, and postmortem evidence of brain infarcts: findings from the Nun Study.

PubMed

Greiner, P A; Snowdon, D A; Greiner, L H

1999-07-01

Self-rated function is a new global measure. Previous findings suggest that self-rated function predicts future functional decline and is strongly associated with all-cause mortality. We hypothesized that the strength of the relationship of self-rated function to all-cause mortality was in part due to functional decline, such as would occur with brain infarcts. Self-ratings of function and health (on a 5-point scale, ranging from excellent to poor) were assessed annually on 630 participants in the Nun Study. Mortality surveillance extended from October 31, 1991 to March 1, 1998, and, among those who died, neuropathological examination determined postmortem evidence of brain infarcts. Cox regression modeling with self-rated function and health as time-dependent covariates and stratification by assessment period were used in these analyses. Self-rated function and health ratings of good, fair, and poor were significantly associated with doubling of the risk of mortality, compared with ratings of very good and excellent. Self-rated function ratings of fair or poor were associated with a threefold increase in the risk of mortality with brain infarcts, but self-rated function and health ratings of fair and poor were comparable in their association with all-cause mortality and mortality without brain infarcts. Self-rated function was significantly associated with mortality with brain infarcts, suggesting that brain infarcts may be experienced as functional loss but not recognized or labeled as disease. Our results suggest that self-rated function and health should be explored simultaneously in future research.

Myocardial infarction size and location: a comparative study of epicardial isopotential mapping, thallium-201 scintigraphy, electrocardiography and vectorcardiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toyama, S.; Suzuki, K.; Takahashi, T.

1987-07-01

Based on epicardial isopotential mapping (the Ep Map), which was calculated from body surface isopotential mapping (the Body Map) with Yamashita's method, using the finite element technique, we predicted the location and size of the abnormal depolarized area (the infarcted area) in 19 clinical cases of anterior and 18 cases of inferoposterior infarction. The prediction was done using Toyama's diagnostic method, previously reported. The accuracy of the prediction by the Ep Map was assessed by comparing it with findings from thallium-201 scintigraphy (SCG), electrocardiography (ECG) and vectorcardiography (VCG). In all cases of anterior infarction, the location of the abnormal depolarizedmore » areas determined on the Ep Map, which was localized at the anterior wall along the anterior intraventricular septum, agreed with the location of the abnormal findings obtained by SCG, ECG and VCG. For all inferoposterior infarction cases, the abnormal depolarized areas were localized at the posterior wall and the location also coincided with that of the abnormal findings obtained by SCG, ECG and VCG. Furthermore, we ranked and ordered the size of the abnormal depolarized areas, which were predicted by the Ep Map for both anterior and inferoposterior infarction cases. In the cases of anterior infarction, the order of the size of the abnormal depolarized area by the Ep Map was correlated to the size of the abnormal findings by SCG, as well as to the results from Selvester's QRS scoring system in ECG and to the angle of the maximum QRS vector in the horizontal plane in VCG.« less

Mesenchymal Stem Cells from Fetal Heart Attenuate Myocardial Injury after Infarction: An In Vivo Serial Pinhole Gated SPECT-CT Study in Rats

PubMed Central

Garikipati, Venkata Naga Srikanth; Jadhav, Sachin; Pal, Lily; Prakash, Prem; Dikshit, Madhu; Nityanand, Soniya

2014-01-01

Mesenchymal stem cells (MSC) have emerged as a potential stem cell type for cardiac regeneration after myocardial infarction (MI). Recently, we isolated and characterized mesenchymal stem cells derived from rat fetal heart (fC-MSC), which exhibited potential to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. In the present study, we investigated the therapeutic efficacy of intravenously injected fC-MSC in a rat model of MI using multi-pinhole gated SPECT-CT system. fC-MSC were isolated from the hearts of Sprague Dawley (SD) rat fetuses at gestation day 16 and expanded ex vivo. One week after induction of MI, 2×106 fC-MSC labeled with PKH26 dye (n = 6) or saline alone (n = 6) were injected through the tail vein of the rats. Initial in vivo tracking of 99mTc-labeled fC-MSC revealed a focal uptake of cells in the anterior mid-ventricular region of the heart. At 4 weeks of fC-MSC administration, the cells labeled with PKH26 were located in abundance in infarct/peri-infarct region and the fC-MSC treated hearts showed a significant increase in left ventricular ejection fraction and a significant decrease in the end diastolic volume, end systolic volume and left ventricular myo-mass in comparison to the saline treated group. In addition, fC-MSC treated hearts had a significantly better myocardial perfusion and attenuation in the infarct size, in comparison to the saline treated hearts. The engrafted PKH26-fC-MSC expressed cardiac troponin T, endothelial CD31 and smooth muscle sm-MHC, suggesting their differentiation into all major cells of cardiovascular lineage. The fC-MSC treated hearts demonstrated an up-regulation of cardio-protective growth factors, anti-fibrotic and anti-apoptotic molecules, highlighting that the observed left ventricular functional recovery may be due to secretion of paracrine factors by fC-MSC. Taken together, our results suggest that fC-MSC therapy may be a new therapeutic strategy for MI and multi-pinhole gated SPECT-CT system may be a useful tool to evaluate cardiac perfusion, function and cell tracking after stem cell therapy in acute myocardial injury setting. PMID:24971627

Causes of Troponin Elevation and Associated Mortality in Young Patients.

PubMed

Wu, Candace; Singh, Avinainder; Collins, Bradley; Fatima, Amber; Qamar, Arman; Gupta, Ankur; Hainer, Jon; Klein, Josh; Jarolim, Petr; Di Carli, Marcelo; Nasir, Khurram; Bhatt, Deepak L; Blankstein, Ron

2018-03-01

While increased serum troponin levels are often due to myocardial infarction, increased levels may also be found in a variety of other clinical scenarios. Although these causes of troponin elevation have been characterized in several studies in older adults, they have not been well characterized in younger individuals. We conducted a retrospective review of patients 50 years of age or younger who presented with elevated serum troponin levels to 2 large tertiary care centers between January 2000 and April 2016. Patients with prior known coronary artery disease were excluded. The cause of troponin elevation was adjudicated via review of electronic medical records. All-cause death was determined using the Social Security Administration's death master file. Of the 6081 cases meeting inclusion criteria, 3574 (58.8%) patients had a myocardial infarction, while 2507 (41.2%) had another cause of troponin elevation. Over a median follow-up of 8.7 years, all-cause mortality was higher in patients with nonmyocardial infarction causes of troponin elevation compared with those with myocardial infarction (adjusted hazard ratio [HR] 1.30; 95% confidence interval [CI], 1.15-1.46; P < .001). Specifically, mortality was higher in those with central nervous system pathologies (adjusted HR 2.21; 95% CI, 1.85-2.63; P < .001), nonischemic cardiomyopathies (adjusted HR 1.66; 95% CI, 1.37-2.02; P < .001), and end-stage renal disease (adjusted HR 1.36; 95% CI, 1.07-1.73; P = .013). However, mortality was lower in patients with myocarditis compared with those with an acute myocardial infarction (adjusted HR 0.43; 95% CI:, 0.31-0.59; P < .001). There is a broad differential for troponin elevation in young patients, which differs based on demographic features. Most nonmyocardial infarction causes of troponin elevation are associated with higher all-cause mortality compared with acute myocardial infarction. Copyright © 2018 Elsevier Inc. All rights reserved.

Feasibility of myocardial PET imaging using a benzylguanidine analog: meta-(3-[18F]fluoropropyl)benzylguanidine ([18F]mFPBG).

PubMed

Woo, Sang-Keun; Moon, Byung Seok; Kim, Bom Sahn; Kim, Min Hwan; Lee, Yong Jin; Jung, Jae Ho; Lee, Kyo Chul; Seo, Youngho; Kim, Wook; Lim, Sang Moo; Lee, Byung Chul; Kim, Sang Eun

2018-05-03

Global and regional sympathetic activity in the heart can be evaluated using [ 123 I]meta-iodobenzylguanidine ([ 123 I]mIBG) imaging. However, [ 123 I]mIBG is associated with low image spatial resolution and sensitivity in cardiac imaging. We investigated the capability of an F-18-labeled mIBG derivative, meta-(3-[ 18 F]fluoropropyl)benzylguanidine ([ 18 F]mFPBG), for identifying ischemic and viable myocardium in a rat model of myocardial infarction. The ex vivo biodistribution and in vivo metabolic stability of [ 18 F]mFPBG were investigated in Sprague-Dawley rats. Selective cardiac adrenergic activation was confirmed via a blocking experiment involving pretreatment with desipramine (2 mg kg -1 ), followed by the administration of [ 18 F]mFPBG. Imaging properties of [ 18 F]mFPBG were compared with those of traditional cardiac imaging radiotracers ([ 123 I]mIBG and [ 99m Tc]MIBI) in a rat model of myocardial infarction. Non-invasive image-based measurements of infarct sizes were then compared with histological findings by using Bland-Altman analysis. The differences in infarct sizes determined using histological analysis and [ 18 F]mFPBG PET were -2.55 ± 4.99% (range: -12.33 to 7.22), -2.35 ± 3.32% (range: -8.87 to 4.16), and -3.15 ± 6.16% (range: -15.24 to 8.93) at 5, 20, and 40 min, respectively. Furthermore, [ 18 F]mFPBG PET was superior to traditional imaging methods in assessing the degree of ischemia in areas of myocardial infarction, as well as the actual infarct size. Compared to [ 123 I]mIBG, [ 18 F]mFPBG showed improved spatial resolution and sensitivity in a rat model of myocardial infarction. This result suggested that [ 18 F]mFPBG is a promising cardiac PET imaging agent for potential diagnostic application in PET cardiology. Copyright © 2018 Elsevier Inc. All rights reserved.

The fluoroscopy time, door to balloon time, contrast volume use and prevalence of vascular access site failure with transradial versus transfemoral approach in ST segment elevation myocardial infarction: A systematic review & meta-analysis.

PubMed

Singh, Sukhchain; Singh, Mukesh; Grewal, Navsheen; Khosla, Sandeep

2015-12-01

The authors aimed to conduct first systematic review and meta-analysis in STEMI patients evaluating vascular access site failure rate, fluoroscopy time, door to balloon time and contrast volume used with transradial vs transfemoral approach (TRA vs TFA) for PCI. The PubMed, CINAHL, clinicaltrials.gov, Embase and CENTRAL databases were searched for randomized trials comparing TRA versus TFA. Random effect models were used to conduct this meta-analysis. Fourteen randomized trials comprising 3758 patients met inclusion criteria. The access site failure rate was significantly higher TRA compared to TFA (RR 3.30, CI 2.16-5.03; P=0.000). Random effect inverse variance weighted prevalence rate meta-analysis showed that access site failure rate was predicted to be 4% (95% CI 3.0-6.0%) with TRA versus 1% (95% CI 0.0-1.0 %) with TFA. Door to balloon time (Standardized mean difference [SMD] 0.30 min, 95% CI 0.23-0.37 min; P=0.000) and fluoroscopy time (Standardized mean difference 0.14 min, 95% CI 0.06-0.23 min; P=0.001) were also significantly higher in TRA. There was no difference in the amount of contrast volume used with TRA versus TFA (SMD -0.05 ml, 95% CI -0.14 to 0.04 ml; P=0.275). Statistical heterogeneity was low in cross-over rate and contrast volume use, moderate in fluoroscopy time but high in the door to balloon time comparison. Operators need to consider higher cross-over rate with TRA compared to TFA in STEMI patients while attempting PCI. Fluoroscopy and door to balloon times are negligibly higher with TRA but there is no difference in terms of contrast volume use. Copyright © 2015 Elsevier Inc. All rights reserved.

Laser system refinements to reduce variability in infarct size in the rat photothrombotic stroke model

PubMed Central

Alaverdashvili, Mariam; Paterson, Phyllis G.; Bradley, Michael P.

2015-01-01

Background The rat photothrombotic stroke model can induce brain infarcts with reasonable biological variability. Nevertheless, we observed unexplained high inter-individual variability despite using a rigorous protocol. Of the three major determinants of infarct volume, photosensitive dye concentration and illumination period were strictly controlled, whereas undetected fluctuation in laser power output was suspected to account for the variability. New method The frequently utilized Diode Pumped Solid State (DPSS) lasers emitting 532 nm (green) light can exhibit fluctuations in output power due to temperature and input power alterations. The polarization properties of the Nd:YAG and Nd:YVO4 crystals commonly used in these lasers are another potential source of fluctuation, since one means of controlling output power uses a polarizer with a variable transmission axis. Thus, the properties of DPSS lasers and the relationship between power output and infarct size were explored. Results DPSS laser beam intensity showed considerable variation. Either a polarizer or a variable neutral density filter allowed adjustment of a polarized laser beam to the desired intensity. When the beam was unpolarized, the experimenter was restricted to using a variable neutral density filter. Comparison with existing method(s) Our refined approach includes continuous monitoring of DPSS laser intensity via beam sampling using a pellicle beamsplitter and photodiode sensor. This guarantees the desired beam intensity at the targeted brain area during stroke induction, with the intensity controlled either through a polarizer or variable neutral density filter. Conclusions Continuous monitoring and control of laser beam intensity is critical for ensuring consistent infarct size. PMID:25840363

Urban-Rural Comparisons in Hospital Admission, Treatments, and Outcomes for ST-Segment-Elevation Myocardial Infarction in China From 2001 to 2011: A Retrospective Analysis From the China PEACE Study (Patient-Centered Evaluative Assessment of Cardiac Events).

PubMed

Li, Xi; Murugiah, Karthik; Li, Jing; Masoudi, Frederick A; Chan, Paul S; Hu, Shuang; Spertus, John A; Wang, Yongfei; Downing, Nicholas S; Krumholz, Harlan M; Jiang, Lixin

2017-11-01

In response to urban-rural disparities in healthcare resources, China recently launched a healthcare reform with a focus on improving rural care during the past decade. However, nationally representative studies comparing medical care and patient outcomes between urban and rural areas in China during this period are not available. We created a nationally representative sample of patients in China admitted for ST-segment-elevation myocardial infarction in 2001, 2006, and 2011, using a 2-stage random sampling design in 2 urban and 3 rural strata. In China, evidence-based treatments were provided less often in 2001 in rural hospitals, which had lower volume and less availability of advanced cardiac facilities. However, these differences diminished by 2011 for reperfusion therapy (54% in urban versus 57% in rural; P =0.1) and reversed for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (66% versus 68%; P =0.04) and early β-blockers (56% versus 60%; P =0.01). The risk-adjusted rate of in-hospital death or withdrawal from treatment was not significantly different between urban and rural hospitals in any study year, with an adjusted odds ratio of 1.13 (0.77-1.65) in 2001, 0.99 (0.77-1.27) in 2006, and 0.94 (0.74-1.19) in 2011. Although urban-rural disparities in evidence-based treatment for myocardial infarction in China have largely been eliminated, substantial gaps in quality of care persist in both settings. In addition, urban hospitals providing more resource-intensive care did not achieve better outcomes. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01624883. © 2017 American Heart Association, Inc.

Perfusion weighted imaging and its application in stroke

NASA Astrophysics Data System (ADS)

Li, Enzhong; Tian, Jie; Han, Ying; Wang, Huifang; Li, Xingfeng; Zhu, Fuping

2003-05-01

To study the technique and application of perfusion weighted imaging (PWI) in the diagnosis and medical treatment of acute stroke, 25 patients were examined by 1.5 T or 1.0 T MRI scanner. The Data analysis was done with "3D Med System" developed by our Lab to process the data and obtain apparent diffusion coefficient (ADC) map, cerebral blood volume (CBV) map, cerebral blood flow (CBF) map as well as mean transit time (MTT) map. In accute stage of stroke, normal or slightly hypointensity in T1-, hyperintensity in T2- and diffusion-weighted images were seen in the cerebral infarction areas. There were hypointensity in CBV map, CBF map and ADC map; and hyperintensity in MTT map that means this infarct area could be saved. If the hyperintensity area in MTT map was larger than the area in diffusion weighted imaging (DWI), the larger part was called penumbra and could be cured by an appropriate thrombolyitic or other therapy. The CBV, CBF and MTT maps are very important in the diagnosis and medical treatment of acute especially hyperacute stroke. Comparing with DWI, we can easily know the situation of penumbra and the effect of curvative therapy. Besides, we can also make a differential diagnosis with this method.

Proteomic analysis of cPKCβII-interacting proteins involved in HPC-induced neuroprotection against cerebral ischemia of mice.

PubMed

Bu, Xiangning; Zhang, Nan; Yang, Xuan; Liu, Yanyan; Du, Jianli; Liang, Jing; Xu, Qunyuan; Li, Junfa

2011-04-01

Hypoxic preconditioning (HPC) initiates intracellular signaling pathway to provide protection against subsequent cerebral ischemic injuries, and its mechanism may provide molecular targets for therapy in stroke. According to our study of conventional protein kinase C βII (cPKCβII) activation in HPC, the role of cPKCβII in HPC-induced neuroprotection and its interacting proteins were determined in this study. The autohypoxia-induced HPC and middle cerebral artery occlusion (MCAO)-induced cerebral ischemia mouse models were prepared as reported. We found that HPC reduced 6 h MCAO-induced neurological deficits, infarct volume, edema ratio and cell apoptosis in peri-infarct region (penumbra), but cPKCβII inhibitors Go6983 and LY333531 blocked HPC-induced neuroprotection. Proteomic analysis revealed that the expression of four proteins in cytosol and eight proteins in particulate fraction changed significantly among 49 identified cPKCβII-interacting proteins in cortex of HPC mice. In addition, HPC could inhibit the decrease of phosphorylated collapsin response mediator protein-2 (CRMP-2) level and increase of CRMP-2 breakdown product. TAT-CRMP-2 peptide, which prevents the cleavage of endogenous CRMP-2, could inhibit CRMP-2 dephosphorylation and proteolysis as well as the infarct volume of 6 h MCAO mice. This study is the first to report multiple cPKCβII-interacting proteins in HPC mouse brain and the role of cPKCβII-CRMP-2 in HPC-induced neuroprotection against early stages of ischemic injuries in mice. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Neuroprotection by dimethyloxalylglycine following permanent and transient focal cerebral ischemia in rats

PubMed Central

Nagel, Simon; Papadakis, Michalis; Chen, Ruoli; Hoyte, Lisa C; Brooks, Keith J; Gallichan, Daniel; Sibson, Nicola R; Pugh, Chris; Buchan, Alastair M

2011-01-01

Dimethyloxalylglycine (DMOG) is an inhibitor of prolyl-4-hydroxylase domain (PHD) enzymes that regulate the stability of hypoxia-inducible factor (HIF). We investigated the effect of DMOG on the outcome after permanent and transient middle cerebral artery occlusion (p/tMCAO) in the rat. Before and after pMCAO, rats were treated with 40 mg/kg, 200 mg/kg DMOG, or vehicle, and with 40 mg/kg or vehicle after tMCAO. Serial magnetic resonance imaging (MRI) was performed to assess infarct evolution and regional cerebral blood flow (rCBF). Both doses significantly reduced infarct volumes, but only 40 mg/kg improved the behavior after 24 hours of pMCAO. Animals receiving 40 mg/kg were more likely to maintain rCBF values above 30% from the contralateral hemisphere within 24 hours of pMCAO. DMOG after tMCAO significantly reduced the infarct volumes and improved behavior at 24 hours and 8 days and also improved the rCBF after 24 hours. A consistent and significant upregulation of both mRNA and protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) was associated with the observed neuroprotection, although this was not consistently related to HIF-1α levels at 24 hours and 8 days. Thus, DMOG afforded neuroprotection both at 24 hours after pMCAO and at 24 hours and 8 days after tMCAO. This effect was associated with an increase of VEGF and eNOS and was mediated by improved rCBF after DMOG treatment. PMID:20407463

Collagen remodeling after myocardial infarction in the rat heart.

PubMed Central

Cleutjens, J. P.; Verluyten, M. J.; Smiths, J. F.; Daemen, M. J.

1995-01-01

In this study changes in the amount and distribution of types I and III collagen mRNA and protein were investigated in the rat heart after induction of a left ventricular myocardial infarction (MI). Sham operated rats served as controls. The animals were sacrificed at different time intervals after operation. Northern blotting of cardiac RNA and hybridization with cDNA probes for types I and III procollagen revealed a 5- to 15-fold increase in the infarcted left ventricle. Type III procollagen mRNA levels were already increased at day 2 after MI, whereas type I procollagen mRNA followed this response at day 4 after MI. This increase was sustained for at least 21 days in the infarcted left ventricle for type III procollagen mRNA, whereas type 1 procollagen mRNA levels were still elevated at 90 days after MI. In the noninfarcted right ventricle a 5- to 7-fold increase was observed for both type I and type III procollagen mRNA levels, but only at day 4 after MI. In the non-infarcted septum a transient increase was observed for type I procollagen mRNA from day 7-21 (4- to 5-fold increase) and a decline to sham levels thereafter. In the septum type III procollagen mRNA levels were only elevated at 7 days after MI (4- to 5-fold increase) compared with sham operated controls. In situ hybridization with the same types I and III procollagen probes showed procollagen mRNA-producing cells in the infarcted area around necrotic cardiomyocytes, and in the interstitial cells in the non-infarcted part of the myocardium. No labeling was detected above cardiomyocytes. Combined in situ hybridization and immunohistochemistry showed that the collagen mRNA producing cells have a myofibroblast-like phenotype in the infarcted myocardium and are fibroblasts in the noninfarcted septum and right ventricle. The increase in types I and III procollagen mRNA in both infarcted and non-infarcted myocardium was followed by an increased collagen deposition, measured by computerized morphometry on sirius red-stained tissue sections as well as by the hydroxyproline assay. In the non-infarcted septum and right ventricle the collagen-positive area was maximal at day 14 (3- to 5-fold increase compared with sham operated controls) and slightly declined at day 21. In the infarcted myocardium the collagen-positive area was 57 +/- 10% at day 14 after MI. Hydroxyproline contents were significantly increased in the noninfarcted septum.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 1 Figure 4 Figure 5 Figure 8 Figure 9 PMID:7639329

Collagen remodeling after myocardial infarction in the rat heart.

PubMed

Cleutjens, J P; Verluyten, M J; Smiths, J F; Daemen, M J

1995-08-01

In this study changes in the amount and distribution of types I and III collagen mRNA and protein were investigated in the rat heart after induction of a left ventricular myocardial infarction (MI). Sham operated rats served as controls. The animals were sacrificed at different time intervals after operation. Northern blotting of cardiac RNA and hybridization with cDNA probes for types I and III procollagen revealed a 5- to 15-fold increase in the infarcted left ventricle. Type III procollagen mRNA levels were already increased at day 2 after MI, whereas type I procollagen mRNA followed this response at day 4 after MI. This increase was sustained for at least 21 days in the infarcted left ventricle for type III procollagen mRNA, whereas type 1 procollagen mRNA levels were still elevated at 90 days after MI. In the noninfarcted right ventricle a 5- to 7-fold increase was observed for both type I and type III procollagen mRNA levels, but only at day 4 after MI. In the non-infarcted septum a transient increase was observed for type I procollagen mRNA from day 7-21 (4- to 5-fold increase) and a decline to sham levels thereafter. In the septum type III procollagen mRNA levels were only elevated at 7 days after MI (4- to 5-fold increase) compared with sham operated controls. In situ hybridization with the same types I and III procollagen probes showed procollagen mRNA-producing cells in the infarcted area around necrotic cardiomyocytes, and in the interstitial cells in the non-infarcted part of the myocardium. No labeling was detected above cardiomyocytes. Combined in situ hybridization and immunohistochemistry showed that the collagen mRNA producing cells have a myofibroblast-like phenotype in the infarcted myocardium and are fibroblasts in the noninfarcted septum and right ventricle. The increase in types I and III procollagen mRNA in both infarcted and non-infarcted myocardium was followed by an increased collagen deposition, measured by computerized morphometry on sirius red-stained tissue sections as well as by the hydroxyproline assay. In the non-infarcted septum and right ventricle the collagen-positive area was maximal at day 14 (3- to 5-fold increase compared with sham operated controls) and slightly declined at day 21. In the infarcted myocardium the collagen-positive area was 57 +/- 10% at day 14 after MI. Hydroxyproline contents were significantly increased in the noninfarcted septum.(ABSTRACT TRUNCATED AT 400 WORDS)

Results of the Croatian Primary Percutaneous Coronary Intervention Network for patients with ST-segment elevation acute myocardial infarction.

PubMed

Nikolić Heitzler, Vjeran; Babic, Zdravko; Milicic, Davor; Bergovec, Mijo; Raguz, Miroslav; Mirat, Jure; Strozzi, Maja; Plazonic, Zeljko; Giunio, Lovel; Steiner, Robert; Starcevic, Boris; Vukovic, Ivica

2010-05-01

The Republic of Croatia, with a gross domestic product per capita of US$11,554 in 2008, is an economically less-developed Western country. The goal of the present investigation was to prove that a well-organized primary percutaneous coronary intervention network in an economically less-developed country equalizes the prospects of all patients with acute ST-segment elevation myocardial infarction at a level comparable to that of more economically developed countries. We prospectively investigated 1,190 patients with acute ST-segment elevation myocardial infarction treated with primary PCI in 8 centers across Croatia (677 nontransferred and 513 transferred). The postprocedural Thrombolysis In Myocardial Infarction flow, in-hospital mortality, and incidence of major adverse cardiovascular events (ie, mortality, pectoral angina, restenosis, reinfarction, coronary artery bypass graft, and cerebrovascular accident rate) during 6 months of follow-up were compared between the nontransferred and transferred subgroups and in the subgroups of older patients, women, and those with cardiogenic shock. In all investigated patients, the average door-to-balloon time was 108 minutes, and the total ischemic time was 265 minutes. Postprocedural Thrombolysis In Myocardial Infarction 3 flow was established in 87.1% of the patients, and the in-hospital mortality rate was 4.4%. No statistically significant difference was found in the results of treatment between the transferred and nontransferred patients overall or in the subgroups of patients >75 years, women, and those with cardiogenic shock. In conclusion, the Croatian Primary Percutaneous Coronary Intervention Network has ensured treatment results of acute ST-segment elevation myocardial infarction comparable to those of randomized studies and registries of more economically developed countries. Copyright 2010 Elsevier Inc. All rights reserved.

Impact on delay times and characteristics of patients undergoing primary percutaneous coronary intervention in the southern metropolitan area of Barcelona after implementation of the infarction code program.

PubMed

Gómez-Hospital, Joan Antoni; Dallaglio, Paolo Domenico; Sánchez-Salado, Jose Carlos; Ariza, Albert; Homs, Silvia; Lorente, Victoria; Ferreiro, Jose Luis; Gomez-Lara, Josep; Romaguera, Rafael; Salazar-Mendiguchía, Joel; Teruel, Luis; Cequier, Ángel

2012-10-01

A standardized protocol of emergent transfer for primary percutaneous coronary intervention for patients with ST elevation myocardial infarction, defined as the Infarction Code, was implemented in June 2009 in the Catalan regional health system. The objective of this study was to evaluate the impact of the new protocol on delay times, number of procedures and clinical characteristics compared with the previous period in the population of patients referred to our hospital. All consecutive patients undergoing primary percutaneous coronary intervention in our hospital were prospectively registered. The clinical characteristics, delay times and mortality in the follow-up of the protocol implementation period (June 2009-May 2010) were analyzed and compared with the previous year (June 2008-May 2009). During the protocol period, 514 patients were included, compared with 241 in the previous year. Age, cardiovascular risk factors, anterior myocardial infarction and procedure characteristics were similar in the 2 groups. The first medical contact to balloon time was lower in the protocol period (median time 120 min vs 88 min; P<.001). Patients in the protocol period showed a trend toward less severe disease (Killip III, rescue angioplasty). The multivariate regression analysis showed a significant association between 1-year mortality and age, Killip class ≥ III at admission, anterior infarction and 3-vessel disease. The introduction of the Infarction Code program increased the number of patients treated by primary percutaneous coronary intervention with a reduction in delay times and better clinical characteristics at presentation. Full English text available from:www.revespcardiol.org. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Cryptogenic Stroke and Nonstenosing Intracranial Calcified Atherosclerosis.

PubMed

Kamel, Hooman; Gialdini, Gino; Baradaran, Hediyeh; Giambrone, Ashley E; Navi, Babak B; Lerario, Michael P; Min, James K; Iadecola, Costantino; Gupta, Ajay

2017-04-01

Because some cryptogenic strokes may result from large-artery atherosclerosis that goes unrecognized as it causes <50% luminal stenosis, we compared the prevalence of nonstenosing intracranial atherosclerotic plaques ipsilateral to cryptogenic cerebral infarcts versus the unaffected side using imaging biomarkers of calcium burden. In a prospective stroke registry, we identified patients with cerebral infarction limited to the territory of one internal carotid artery (ICA). We included patients with stroke of undetermined etiology and, as controls, patients with cardioembolic stroke. We used noncontrast computed tomography to measure calcification in both intracranial ICAs, including qualitative calcium scoring and quantitative scoring utilizing the Agatston-Janowitz (AJ) calcium scoring. Within subjects, the Wilcoxon signed-rank sum test for nonparametric paired data was used to compare the calcium burden in the ICA upstream of the infarction versus the ICA on the unaffected side. We obtained 440 calcium measures from 110 ICAs in 55 patients. Among 34 patients with stroke of undetermined etiology, we found greater calcium in the ICA ipsilateral to the infarction (mean Modified Woodcock Visual Scale score, 6.7 ± 4.6) compared with the contralateral side (5.4 ± 4.1) (P = .005). Among 21 patients with cardioembolic stroke, we found no difference in calcium burden ipsilateral to the infarction (6.7 ± 5.9) versus the contralateral side (7.3 ± 6.3) (P = .13). The results were similar using quantitative calcium measurements, including the AJ calcium scores. In patients with strokes of undetermined etiology, the burden of calcified intracranial large-artery plaque was associated with downstream cerebral infarction. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Autologous Fat Used for Facial Filling Can Lead to Massive Cerebral Infarction Through Middle Cerebral Artery or Facial Intracranial Branches.

PubMed

Wang, Xian; Wu, Min; Zhou, Xing; Liu, Hengdeng; Zhang, Yongchao; Wang, Haiping

2018-05-31

Autologous fat injection is a procedure aimed at eliminating grave defects in the skin surface by subcutaneous injection of the patient's fatty tissue. Fat embolism is a rare but severe complication of this procedure, especially cerebral infarction. It is first reported by Thaunat in 2004. were presented to the hospital with sudden unconsciousness and left limb weakness in 24 hours after facial fat injection. Brain computed tomography and magnetic resonance imaging were performed immediately after admission. Frontal temporoparietal decompressive craniectomy plus multiple treatments scheduled for patients. Pictures and videos were taken during follow-up. Figures are edited with Adobe Photograph CS6. Patients were diagnosed with extensive cerebral infarction of the right hemisphere through the middle cerebral artery or facial-intracranial branches. Routine cosmetic procedures of facial fat injections could cause devastating and even fatal complications to patients. The small volume of fat grafts can be inserted through the internal carotid artery or go through the communicating branches between the facial artery and the intracranial artery into the brain.

Sacubitril and valsartan protect from experimental myocardial infarction by ameliorating oxidative damage in Wistar rats.

PubMed

Imran, Mohd; Hassan, Md Quamrul; Akhtar, Md Sayeed; Rahman, Obaid; Akhtar, M; Najmi, Abul Kalam

2018-03-29

Sacubitril (SAC), a neprilysin inhibitor prevent degradation of neprilysin and activate cGMP signaling pathways leading to rise in blood volume concurrent to blood pressure by means of vasoactive peptides, adrenomedullin, and bradykinin. The aim of this study was to evaluate the anti-ischemic effects of SAC through inhibiting neprilysin in isoproterenol (ISO) induced myocardial infarction (MI) in Wistar albino rats. ISO (85 mg/kg) was injected subcutaneously at the end of 14 days pre-treatment with SAC and valsartan (VAL). Biochemical investigation revealed that SAC along with VAL significantly prevented the antioxidant enzymes (SOD, Catalase, GR, GPx, GST, and GSH) degradation and malondialdehyde (MDA) induced by ISO intoxication in Wistar rats. Along with this, cardiac biomarkers (LDH, CK-MB, ALT, AST, and ALP) were also significantly ameliorated by SACand VAL in ISO-treated rats. Concurrently, decreased infarction area (IA)and marked reduction in myofibril damage by SACand VAL further supported its protective benefits in MI. Taken together, the results suggest that inhibition of enzyme neprilysin alleviated the ISO induces myocardial damage mediated by its strong antioxidant potential.

Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.

PubMed

Snowdon, D A; Greiner, L H; Mortimer, J A; Riley, K P; Greiner, P A; Markesbery, W R

1997-03-12

To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. Convents in the Midwestern, Eastern, and Southern United States. A total of 102 college-educated women aged 76 to 100 years. Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7, 95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.

Differential Clinical Implications of High-Degree Atrioventricular Block Complicating ST-Segment Elevation Myocardial Infarction according to the Location of Infarction in the Era of Primary Percutaneous Coronary Intervention

PubMed Central

Kim, Kyung Hwan; Ahn, Youngkeun; Kim, Young Jo; Cho, Myeong Chan; Kim, Wan

2016-01-01

Background and Objectives The clinical implication of high-degree (second- and third-degree) atrioventricular block (HAVB) complicating ST-segment elevation myocardial infarction (STEMI) is ripe for investigation in this era of primary percutaneous coronary intervention (PCI). We sought to address the incidence, predictors and prognosis of HAVB according to the location of infarct in STEMI patients treated with primary PCI. Subjects and Methods A total of 16536 STEMI patients (anterior infarction: n=9354, inferior infarction: n=7692) treated with primary PCI were enrolled from a multicenter registry. We compared in-hospital mortality between patients with HAVB and those without HAVB with anterior or inferior infarction, separately. Multivariate analyses were performed to unearth predictors of HAVB and to identify whether HAVB is independently associated with in-hospital mortality. Results STEMI patients with HAVB showed higher in-hospital mortality than those without HAVB in both anterior (hazard ratio [HR]=9.821, 95% confidence interval [CI]: 4.946-19.503, p<0.001) and inferior infarction (HR=2.819, 95% CI: 2.076-3.827, p<0.001). In multivariate analyses, HAVB was associated with increased in-hospital mortality in anterior myocardial infarction (HR=19.264, 95% CI: 5.804-63.936, p<0.001). However, HAVB in inferior infarction was not an independent predictor of increased in-hospital mortality (HR=1.014, 95% CI: 0.547-1.985, p=0.901). Conclusion In this era of primary PCI, the prognostic impact of HAVB is different according to the location of infarction. Because of recent improvements in reperfusion strategy, the negative prognostic impact of HAVB in inferior STEMI is no longer prominent. PMID:27275168

Assessment of left ventricular ejection fraction by radionuclide angiography. Comparison to echocardiography and serial measurements in patients with myocardial infarction

NASA Technical Reports Server (NTRS)

Schelbert, H. R.; Henning, H.; Orourke, R. A.; Ashburn, W. L.

1975-01-01

Measurements of the left ventricular ejection fraction were compared in patients with previous myocardial infarctions. Left ventricular ejection fraction was measured by the radioisotopic method serially in patients early after an acute myocardial infarction and during the convalescence period. Ultrasound recordings were obtained utilizing a commercially available ultrasonoscope and a 1/9 cm transducer focused at 10 cm with a repetition rate of 1000 impulses per second. All recordings were made on a visicorder oscillography.

Fluorodeoxyglucose /sup 18/F scan in Alzheimer's disease and multi-infarct dementia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, D.F.; Kuhl, D.E.; Hawkins, R.A.

1983-11-01

Patients with Alzheimer's disease and multi-infarct dementia were studied with scans using fluorodeoxyglucose tagged with fluorine 18. The rates of glucose metabolism were calculated. Patients with Alzheimer's dementia showed decreased metabolism in all areas of the brain but with preferential sparing of the primary motor and sensory cortex. Patients with multi-infarct dementia also had global reductions in glucose metabolic rates when compared with normal control subjects, but the areas of hypometabolism were focal and asymmetric.

Quantification of myocardium at risk in ST- elevation myocardial infarction: a comparison of contrast-enhanced steady-state free precession cine cardiovascular magnetic resonance with coronary angiographic jeopardy scores.

PubMed

De Palma, Rodney; Sörensson, Peder; Verouhis, Dinos; Pernow, John; Saleh, Nawzad

2017-07-27

Clinical outcome following acute myocardial infarction is predicted by final infarct size evaluated in relation to left ventricular myocardium at risk (MaR). Contrast-enhanced steady-state free precession (CE-SSFP) cardiovascular magnetic resonance imaging (CMR) is not widely used for assessing MaR. Evidence of its utility compared to traditional assessment methods and as a surrogate for clinical outcome is needed. Retrospective analysis within a study evaluating post-conditioning during ST elevation myocardial infarction (STEMI) treated with coronary intervention (n = 78). CE-SSFP post-infarction was compared with angiographic jeopardy methods. Differences and variability between CMR and angiographic methods using Bland-Altman analyses were evaluated. Clinical outcomes were compared to MaR and extent of infarction. MaR showed correlation between CE-SSFP, and both BARI and APPROACH scores of 0.83 (p < 0.0001) and 0.84 (p < 0.0001) respectively. Bias between CE-SSFP and BARI was 1.1% (agreement limits -11.4 to +9.1). Bias between CE-SSFP and APPROACH was 1.2% (agreement limits -13 to +10.5). Inter-observer variability for the BARI score was 0.56 ± 2.9; 0.42 ± 2.1 for the APPROACH score; -1.4 ± 3.1% for CE-SSFP. Intra-observer variability was 0.15 ± 1.85 for the BARI score; for the APPROACH score 0.19 ± 1.6; and for CE-SSFP -0.58 ± 2.9%. Quantification of MaR with CE-SSFP imaging following STEMI shows high correlation and low bias compared with angiographic scoring and supports its use as a reliable and practical method to determine myocardial salvage in this patient population. Clinical trial registration information for the parent clinical trial: Karolinska Clinical Trial Registration (2008) Unique identifier: CT20080014. Registered 04 th January 2008.

Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-2.

PubMed

Morihara, Ryuta; Yamashita, Toru; Kono, Syoichiro; Shang, Jingwei; Nakano, Yumiko; Sato, Kota; Hishikawa, Nozomi; Ohta, Yasuyuki; Heitmeier, Stefan; Perzborn, Elisabeth; Abe, Koji

2017-09-01

This study aimed to assess the risk of intracerebral hemorrhage (ICH) after tissue-type plasminogen activator (tPA) treatment in rivaroxaban compared with warfarin-pretreated male Wistar rat brain after ischemia in relation to activation profiles of protease-activated receptor-1, -2, -3, and -4 (PAR-1, -2, -3, and -4). After pretreatment with warfarin (0.2 mg/kg/day), low-dose rivaroxaban (60 mg/kg/day), high-dose rivaroxaban (120 mg/kg/day), or vehicle for 14 days, transient middle cerebral artery occlusion was induced for 90 min, followed by reperfusion with tPA (10 mg/kg/10 ml). Infarct volume, hemorrhagic volume, immunoglobulin G leakage, and blood parameters were examined. Twenty-four hours after reperfusion, immunohistochemistry for PARs was performed in brain sections. ICH volume was increased in the warfarin-pretreated group compared with the rivaroxaban-treated group. PAR-1, -2, -3, and -4 were widely expressed in the normal brain, and their levels were increased in the ischemic brain, especially in the peri-ischemic lesion. Warfarin pretreatment enhanced the expression of PAR-1 and PAR-2 in the peri-ischemic lesion, whereas rivaroxaban pretreatment did not. The present study shows a lower risk of brain hemorrhage in rivaroxaban-pretreated compared with warfarin-pretreated rats following tPA administration to the ischemic brain. It is suggested that the relative downregulation of PAR-1 and PAR-2 by rivaroxaban compared with warfarin pretreatment might be partly involved in the mechanism of reduced hemorrhagic complications in patients receiving rivaroxaban in clinical trials. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Early Cerebral Small Vessel Disease and Brain Volume, Cognition, and Gait

PubMed Central

Smith, Eric E; O'Donnell, Martin; Dagenais, Gilles; Lear, Scott A; Wielgosz, Andreas; Sharma, Mukul; Poirier, Paul; Stotts, Grant; Black, Sandra E; Strother, Stephen; Noseworthy, Michael D; Benavente, Oscar; Modi, Jayesh; Goyal, Mayank; Batool, Saima; Sanchez, Karla; Hill, Vanessa; McCreary, Cheryl R; Frayne, Richard; Islam, Shofiqul; DeJesus, Jane; Rangarajan, Sumathy; Teo, Koon; Yusuf, Salim

2015-01-01

Objective Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI). Methods Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND). Results Mean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum. Interpretation Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life. Ann Neurol 2015;77:251–261 PMID:25428654

Illness consequences after myocardial infarction: problems with physical functioning and return to work.

PubMed

Brink, Eva; Brändström, Yvonne; Cliffordsson, Christina; Herlitz, Johan; Karlson, Björn W

2008-12-01

This paper is a report of a study to explore health problems, physical and mental functioning, and physical activity in working-age patients after myocardial infarction, in order to assess the possible effects of these factors on return to work. A diagnosis of myocardial infarction may discourage patients from continuing an active working life. Enabling myocardial infarction patients to return to work has benefits for both individuals and society. A convenience sample was recruited of 88 patients,

Brain metabolite changes in patients with type 2 diabetes and cerebral infarction using proton magnetic resonance spectroscopy.

PubMed

Zhang, Min; Sun, Xinhai; Zhang, Zhengjun; Meng, Qiang; Wang, Yuzhong; Chen, Jing; Ma, Xueqin; Geng, Houfa; Sun, Lin

2014-01-01

The aim of this study was to investigate the possible brain metabolic alterations in patients with type 2 diabetes mellitus (T2DM) and cerebral infarction (DMCI) using proton magnetic resonance spectroscopy (MRS). Thirty-four patients with T2DM and DMCI were scanned together with 33 patients with nondiabetic cerebral infarction (NDCI) on a 1.5-T MRI/MRS imager. Voxels were placed in the infarcted area and the contralateral normal area in the basal ganglia. N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and lactate (Lac)/Cr ratios were calculated. Cerebral NAA/Cr ratios in the infarcted area were lower than those in the contralateral normal area of the NDCI group. There was a significant decrease in NAA/Cr in the infarcted area of the DMCI group as compared with the infarcted area of the NDCI group. NAA/Cr ratios in the contralateral normal area of DMCI group were lower than those of the NDCI group. Lac/Cr ratios were increased in the infarcted area of both the DMCI group and NDCI group, and Lac/Cr ratios tended to be higher in the infarcted area of the DMCI group than those of the NDCI group. Glycosylated hemoglobin (HbA1c) levels were negatively correlated with NAA/Cr ratios. The study suggested that the metabolite changes were different between DMCI patients and NDCI patients, which may provide important information in the treatment of DMCI.

Temporal trends in incidence of myocardial infarction and ischemic stroke by socioeconomic position in Sweden 1987-2010.

PubMed

Malki, Ninoa; Koupil, Ilona; Eloranta, Sandra; Weibull, Caroline E; Tiikkaja, Sanna; Ingelsson, Erik; Sparén, Pär

2014-01-01

We analyzed temporal trends in the incidence of myocardial infarction and ischemic stroke in Sweden by socioeconomic position and investigated whether social inequalities in incidence of these diseases changed over time. We studied a cohort of almost three million Swedish residents born between 1932 and 1960 followed from 1987 until 2010. Incident cases of myocardial infarction and ischemic stroke were identified in the Swedish National Inpatient Register and Cause of Death Register. Socioeconomic position was retrieved from the Population and Housing Censuses. Incidence rates of myocardial infarction and ischemic stroke and incidence rate ratios comparing levels of socioeconomic position were estimated using flexible parametric survival models adjusted for calendar year, attained age, sex, and birth country. The overall incidences of myocardial infarction and ischemic stroke decreased over time among men, but were stable over time among women. With regard to ischemic stroke incidence, socioeconomic inequality increased over time in the age group 55 to 59: the incidence rate ratios for low manual compared to high non-manual increased from 1.3 (95% CI: 1.2-1.4) in 1997 to 1.5 (1.4-1.7) in 2010 among men, and from 1.4 (1.3-1.6) in 1997 to 2.1 (1.8-2.5) in 2010 among women. The socioeconomic inequality in incidence of myocardial infarction was stable over time for both men and women. There was a decrease in myocardial infarction and ischemic stroke incidence over time among men but no significant change for women. Our study highlights existing, and in some cases increasing, social inequalities in the incidence of cardiovascular diseases.

Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats

PubMed Central

Rocha, Juraci Aparecida; Ribeiro, Susan Pereira; França, Cristiane Miranda; Coelho, Otávio; Alves, Gisele; Kallás, Esper Georges; Irigoyen, Maria Cláudia

2016-01-01

We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg−1·day−1) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups—denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups—were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3+ cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4+CD25+FOXP3+), and a less extreme decrease in conventional T cells (CD25+FOXP3−) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats. PMID:26791829

Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats.

PubMed

Rocha, Juraci Aparecida; Ribeiro, Susan Pereira; França, Cristiane Miranda; Coelho, Otávio; Alves, Gisele; Lacchini, Silvia; Kallás, Esper Georges; Irigoyen, Maria Cláudia; Consolim-Colombo, Fernanda M

2016-04-15

We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg(-1)·day(-1)) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups-denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3(+)cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4(+)CD25(+)FOXP3(+)), and a less extreme decrease in conventional T cells (CD25(+)FOXP3(-)) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats. Copyright © 2016 the American Physiological Society.

Sitagliptin attenuates sympathetic innervation via modulating reactive oxygen species and interstitial adenosine in infarcted rat hearts.

PubMed

Lee, Tsung-Ming; Chen, Wei-Ting; Yang, Chen-Chia; Lin, Shinn-Zong; Chang, Nen-Chung

2015-02-01

We investigated whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuates arrhythmias through inhibiting nerve growth factor (NGF) expression in post-infarcted normoglycemic rats, focusing on adenosine and reactive oxygen species production. DPP-4 bound adenosine deaminase has been shown to catalyse extracellular adenosine to inosine. DPP-4 inhibitors increased adenosine levels by inhibiting the complex formation. Normoglycemic male Wistar rats were subjected to coronary ligation and then randomized to either saline or sitagliptin in in vivo and ex vivo studies. Post-infarction was associated with increased oxidative stress, as measured by myocardial superoxide, nitrotyrosine and dihydroethidium fluorescent staining. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated infarcted rats compared with sham. Compared with vehicle, infarcted rats treated with sitagliptin significantly increased interstitial adenosine levels and attenuated oxidative stress. Sympathetic hyperinnervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Ex vivo studies showed a similar effect of erythro-9-(2-hydroxy-3-nonyl) adenine (an adenosine deaminase inhibitor) to sitagliptin on attenuated levels of superoxide and NGF. Furthermore, the beneficial effects of sitagliptin on superoxide anion production and NGF levels can be reversed by 8-cyclopentyl-1,3-dipropulxanthine (adenosine A1 receptor antagonist) and exogenous hypoxanthine. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation via adenosine A1 receptor and xanthine oxidase-dependent pathways, which converge through the attenuated formation of superoxide in the non-diabetic infarcted rats. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Tomato (Lycopersicon esculentum) or lycopene supplementation attenuates ventricular remodeling after myocardial infarction through different mechanistic pathways.

PubMed

Pereira, Bruna L B; Reis, Patrícia P; Severino, Fábio E; Felix, Tainara F; Braz, Mariana G; Nogueira, Flávia R; Silva, Renata A C; Cardoso, Ana C; Lourenço, Maria A M; Figueiredo, Amanda M; Chiuso-Minicucci, Fernanda; Azevedo, Paula S; Polegato, Bertha F; Okoshi, Katashi; Fernandes, Ana A H; Paiva, Sergio A R; Zornoff, Leonardo A M; Minicucci, Marcos F

2017-08-01

The objective of this study was to evaluate the influence of tomato or lycopene supplementation on cardiac remodeling after myocardial infarction (MI). Male Wistar rats were assigned to four groups: the sham group (animals that underwent simulated surgery) that received a standard chow (S; n=18), the infarcted group that received a standard chow (MI; n=13), the infarcted group supplemented with lycopene (1 mg of lycopene/kg body weight/day) (MIL; n=16) and the infarcted group supplemented with tomato (MIT; n=16). After 3 months, morphological, functional and biochemical analyses were performed. The groups MIL and MIT showed decreased interstitial fibrosis induced by infarction. Tomato supplementation attenuated the hypertrophy induced by MI. In addition, tomato and lycopene improved diastolic dysfunction evaluated by echocardiographic and isolated heart studies, respectively. The MI group showed higher levels of cardiac TNF-α compared to the MIL and MIT groups. Decreased nuclear factor E2-related factor 2 was measured in the MIL group. Lipid hydroperoxide levels were higher in the infarcted groups; however, the MIT group had a lower concentration than did the MI group [S=223±20.8, MI=298±19.5, MIL=277±26.6, MIT=261±28.8 (nmol/g); n=8; P<.001]. We also examined left ventricle miRNA expression; when compared to the S group, the MIL group uniquely down-regulated the expression of eight miRNAs. No miRNA was found to be up-regulated uniquely in the MIT and MIL groups. In conclusion, tomato or lycopene supplementation attenuated the cardiac remodeling process and improved diastolic function after MI. However, the effect of lycopene and tomato supplementation occurred through different mechanistic pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect and Safety of Morphine Use in Acute Anterior ST-Segment Elevation Myocardial Infarction.

PubMed

Bonin, Mickael; Mewton, Nathan; Roubille, Francois; Morel, Olivier; Cayla, Guillaume; Angoulvant, Denis; Elbaz, Meyer; Claeys, Marc J; Garcia-Dorado, David; Giraud, Céline; Rioufol, Gilles; Jossan, Claire; Ovize, Michel; Guerin, Patrice

2018-02-10

Morphine is commonly used to treat chest pain during myocardial infarction, but its effect on cardiovascular outcome has never been directly evaluated. The aim of this study was to examine the effect and safety of morphine in patients with acute anterior ST-segment elevation myocardial infarction followed up for 1 year. We used the database of the CIRCUS (Does Cyclosporine Improve Outcome in ST Elevation Myocardial Infarction Patients) trial, which included 969 patients with anterior ST-segment elevation myocardial infarction, admitted for primary percutaneous coronary intervention. Two groups were defined according to use of morphine preceding coronary angiography. The composite primary outcome was the combined incidence of major adverse cardiovascular events, including cardiovascular death, heart failure, cardiogenic shock, myocardial infarction, unstable angina, and stroke during 1 year. A total of 554 (57.1%) patients received morphine at first medical contact. Both groups, with and without morphine treatment, were comparable with respect to demographic and periprocedural characteristics. There was no significant difference in major adverse cardiovascular events between patients who received morphine compared with those who did not (26.2% versus 22.0%, respectively; P =0.15). The all-cause mortality was 5.3% in the morphine group versus 5.8% in the no-morphine group ( P =0.89). There was no difference between groups in infarct size as assessed by the creatine kinase peak after primary percutaneous coronary intervention (4023±118 versus 3903±149 IU/L; P =0.52). In anterior ST-segment elevation myocardial infarction patients treated by primary percutaneous coronary intervention, morphine was used in half of patients during initial management and was not associated with a significant increase in major adverse cardiovascular events at 1 year. © 2018 The Authors and Hospices Civils de Lyon. Published on behalf of the American Heart Association, Inc., by Wiley.

Subacute cardiac rubidium-82 positron emission tomography (82Rb-PET) to assess myocardial area at risk, final infarct size, and myocardial salvage after STEMI.

PubMed

Ghotbi, Adam Ali; Kjaer, Andreas; Nepper-Christensen, Lars; Ahtarovski, Kiril Aleksov; Lønborg, Jacob Thomsen; Vejlstrup, Niels; Kyhl, Kasper; Christensen, Thomas Emil; Engstrøm, Thomas; Kelbæk, Henning; Holmvang, Lene; Bang, Lia E; Ripa, Rasmus Sejersten; Hasbak, Philip

2018-06-01

Determining infarct size and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) is important when assessing the efficacy of new reperfusion strategies. We investigated whether rest 82 Rb-PET myocardial perfusion imaging can estimate area at risk, final infarct size, and myocardial salvage index when compared to cardiac SPECT and magnetic resonance (CMR). Twelve STEMI patients were injected with 99m Tc-Sestamibi intravenously immediate prior to reperfusion. SPECT, 82 Rb-PET, and CMR imaging were performed post-reperfusion and at a 3-month follow-up. An automated algorithm determined area at risk, final infarct size, and hence myocardial salvage index. SPECT, CMR, and PET were performed 2.2 ± 0.5, 34 ± 8.5, and 32 ± 24.4 h after reperfusion, respectively. Mean (± SD) area at risk were 35.2 ± 16.6%, 34.7 ± 11.3%, and 28.1 ± 16.1% of the left ventricle (LV) in SPECT, CMR, and PET, respectively, P = 0.04 for difference. Mean final infarct size estimates were 12.3 ± 15.4%, 13.7 ± 10.4%, and 11.9 ± 14.6% of the LV in SPECT, CMR, and PET imaging, respectively, P = .72. Myocardial salvage indices were 0.64 ± 0.33 (SPECT), 0.65 ± 0.20 (CMR), and 0.63 ± 0.28 (PET), (P = .78). 82 Rb-PET underestimates area at risk in patients with STEMI when compared to SPECT and CMR. However, our findings suggest that PET imaging seems feasible when assessing the clinical important parameters of final infarct size and myocardial salvage index, although with great variability, in a selected STEMI population with large infarcts. These findings should be confirmed in a larger population.

Punjabi Sikh patients' cardiac rehabilitation experiences following myocardial infarction: a qualitative analysis.

PubMed

Galdas, Paul M; Kang, H Bindy K

2010-11-01

To explore the cardiac rehabilitation experiences of Punjabi Sikh patients post myocardial infarction. Punjabi Sikh people are at significantly higher risk of mortality from myocardial infarction compared with those of European descent. Punjabi Sikh patients' participation in cardiac rehabilitation post myocardial infarction is therefore likely to yield considerable benefits. However, uptake of cardiac rehabilitation by South Asian people has been reported to be modest. Previous investigators have seldom provided insight into experiences of Punjabi Sikh patients post myocardial infarction and the steps that can be taken to improve the appropriateness of cardiac rehabilitation programmes for this at-risk patient group. Interpretive qualitative design. In-depth interviews, based on the McGill Illness Narrative Interview schedule, with 15 Punjabi Sikh patients post myocardial infarction attending a cardiac rehabilitation programme in British Columbia, Canada, were conducted; thematic analysis using grounded theory methods of coding and constant comparative analysis was employed. Four mutually exclusive themes emerged relating to the salient aspects of participants' cardiac rehabilitation experience: 'making sense of the diagnosis', 'practical dietary advice', 'ongoing interaction with peers and the multi-disciplinary team' and 'transport and attendance'. The themes identified point towards some of the ingredients necessary for providing culturally appropriate cardiac rehabilitation interventions for Punjabi Sikh patients following myocardial infarction. The findings highlight the importance of providing culturally relevant rehabilitation advice about diet and lifestyle changes and providing time for ongoing dialogue with support from health care professionals and peers. The findings from this study also illustrate the need to avoid generalisations about the impact religious beliefs may have on South Asian individuals' willingness to adhere to cardiac rehabilitation advice and make lifestyle adjustments. This study raises awareness of some of the salient features of experiences of Punjabi Sikh patients with post myocardial infarction that can help guide nurses to provide culturally appropriate cardiac rehabilitation and coronary health promotion. © 2010 Blackwell Publishing Ltd.

[Seasonal variations in the myocardial infarction incidence and possible effects of geomagnetic micropulsations on the cardiovascular system in humans].

PubMed

Kleĭmenova, N G; Kozyreva, O V; Breus, T K; Rapoport, S I

2007-01-01

The analysis of the ambulance calls in Moscow, related to myocardial infarction (85.000 events), sudden death (71.700 events), and hypertension crises (165.500 events) over the period of 1979-1981 demonstrated their clear seasonal variations with a profound summer minimum and a winter maximum. The same results were obtained in the analysis of statistical monthly data on sudden death from infarction in Bulgaria over the period of 15 years (1970-1985). However, there are a great number of clinical and statistical studies confirming the rises in the incidence of myocardial infarction, hypertension crise, and sudden death during geomagnetic disturbances, which have maximum occurrence near equinox, not in winter. In order to explain this contradiction, we suggested that one of critical factors that affect the human cardiovascular system is geomagnetic micropulsations Pc1 having the frequency comparable with the frequency of heart rate beatings and winter maximum in their occurrence. The results of a comparative analysis of data of ambulance calls in Moscow related to myocardial infarction and sudden death and the catalog of Pc1 observations at the geophysical observatory "Borok" (Yaroslavl region) are presented. It is shown that in approximately 70% of days with an anomalously large number of ambulance calls related to myocardial infarction, Pc1 micropulsations have been registered. The probability of simultaneous occurrence of myocardial infarction and Pc1 in the winter season was 1.5 times greater than their accidental coincidence. Moreover, it was found that in winter the effects of magnetic storms and Pc1 IM(A) were much higher than in summer. We suggested that one of possible reasons for the seasonal variations in the occurrence of myocardial infarction is an increase in the production of the pineal hormone melatonin in winter which leads to an unstable state of the human organism and an increase in its sensitivity to the effect of geomagnetic pulsations.

Stem cells in cardiac repair.

PubMed

Henning, Robert J

2011-01-01

Myocardial infarction is the leading cause of death among people in industrialized nations. Although the heart has some ability to regenerate after infarction, myocardial restoration is inadequate. Consequently, investigators are currently exploring the use of human embryonic stem cells (hESCs), skeletal myoblasts and adult bone marrow stem cells to limit infarct size. hESCs are pluripotent cells that can regenerate myocardium in infarcted hearts, attenuate heart remodeling and contribute to left ventricle (LV) systolic force development. Since hESCs can form heart teratomas, investigators are differentiating hESCs toward cardiac progenitor cells prior to transplantation into hearts. Large quantities of hESCs cardiac progenitor cells, however, must be generated, immune rejection must be prevented and grafts must survive over the long term to significantly improve myocardial performance. Transplanted autologous skeletal myoblasts can survive in infarcted myocardium in small numbers, proliferate, differentiate into skeletal myofibers and increase the LV ejection fraction. These cells, however, do not form electromechanical connections with host cardiomyocytes. Consequently, electrical re-entry can occur and cause cardiac arrhythmias. Autologous bone marrow mononuclear cells contain hematopoietic and mesenchymal stem cells. In several meta-analyses, patients with coronary disease who received autologous bone marrow cells by intracoronary injection show significant 3.7% (range: 1.9-5.4%) increases in LV ejection fraction, decreases in LV end-systolic volume of -4.8 ml (range: -1.4 to -8.2 ml) and reductions in infarct size of 5.5% (-1.9 to -9.1%), without experiencing arrhythmias. Bone marrow cells appear to release biologically active factors that limit myocardial damage. Unfortunately, bone marrow cells from patients with chronic diseases propagate poorly and can die prematurely. Substantial challenges must be addressed and resolved to advance the use of stem cells in cardiac repair including identifying the optimal stem cell(s) that permit transplantation without requirements for host immune suppression; timing of stem cell transplantation that maximizes chemoattraction of stem cells to infarcts; and determining the optimal technique for injecting stem cells for cardiac repair. Techniques must be developed to enhance survival and propagation of stem cells in the myocardium. These studies will require close cooperation and interaction of scientists and clinicians. Cell-based cardiac repair in the 21st century will offer new hope for millions of patients worldwide with myocardial infarctions who, otherwise, would suffer from the relentless progression of heart disease to heart failure and death.

Refined ambient PM2.5 exposure surrogates and the risk of myocardial infarction

EPA Science Inventory

Using a case-crossover study design and conditional logistic regression, we compared the relative odds of transmural (full-wall) myocardial infarction (MI) calculated using exposure surrogates that account for human activity patterns and the indoor transport of ambient PM_2....

High resolution magnetic resonance imaging in pathogenesis diagnosis of single lenticulostriate infarction with nonstenotic middle cerebral artery, a retrospective study.

PubMed

Sun, Li-Li; Li, Zhong-Hao; Tang, Wen-Xiong; Liu, Lei; Chang, Fei-Yan; Zhang, Xue-Bin; Ye, Wei-Jie; Lu, Shuo; Liu, Zun-Jing; Zhu, Xian-Jin

2018-04-25

It is usually difficult to identify stroke pathogenesis for single lenticulostriate infarction with nonstenotic middle cerebral artery (MCA). Our aim is to differentiate the two pathogeneses, non-branch atheromatous small vessel disease and branch atheromatous disease (BAD) by high-resolution magnetic resonance imaging (HR-MRI). Thirty-two single lenticulostriate infarction patients with nonstenotic MCA admitted to the China-Japan Friendship Hospital from December 2014 to August 2017 were enrolled for retrospective analysis. National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), atherosclerotic risk factors, imaging features, and the characteristic of MCA vessel wall in HR-MRI were evaluated. MCA plaques were detected in 15(46.9%) patients which implied BAD and 8 of 15 (53.3%) patients had plaques location in upper dorsal side of the vessel wall. Patients with HR-MRI identified plaques had a significantly larger infarction lesion length (1.95 ± 0.86 cm versus 1.38 ± 0.55 cm; P = 0.031) and larger lesion volume (2.95 ± 3.94 cm 3 versus 0.90 ± 0.94 cm 3 ; P = 0.027) than patients without plaques. Patients with HR-MRI identified plaques had a significant higher percentage of proximal lesions than patients without plaques (P = 0.055). However, according to the location of MCA plaques, there were no significant differences in terms of imaging features, NIHSS and mRS. We demonstrated high frequency of MCA atheromatous plaques visualized in single lenticulostriate infarction patients with nonstenotic MCA by using HR-MRI. Patients with HR-MRI identified plaque presented larger infarction lesions and more proximal lesions than patients without plaque, which were consistent with imaging features of BAD. HR-MRI is an important and effective tool for identifying stroke etiology in patients with nonstenotic MCA.

Longitudinal thalamic diffusion changes after middle cerebral artery infarcts

PubMed Central

Herve, D; Molko, N; Pappata, S; Buffon, F; LeBihan, D; Bousser, M; Chabriat, H

2005-01-01

Background: Cerebral infarcts are responsible for functional alterations and microscopic tissue damage at distance from the ischaemic area. Such remote effects have been involved in stroke recovery. Thalamic hypometabolism is related to motor recovery in middle cerebral artery (MCA) infarcts but little is known concerning the tissue changes underlying these metabolic changes. Diffusion tensor imaging (DTI) is highly sensitive to microstructural tissue alterations and can be used to quantify in vivo the longitudinal microscopic tissue changes occurring in the thalamus after MCA infarcts in humans. Methods: Nine patients underwent DTI after an isolated MCA infarct. Mean diffusivity (MD), fractional anisotropy (FA), and thalamic region volume were measured from the first week to the sixth month after stroke onset in these patients and in 10 age matched controls. Results: MD significantly increased in the ipsilateral thalamus between the first and the sixth month (0.766x10–3 mm2/s first month; 0.792x10–3 mm2/s third month; 0.806x10–3 mm2/s sixth month). No significant modification of FA was detected. In six patients, the ipsilateral/contralateral index of MD was higher than the upper limit of the 95% CI calculated in 10 age matched controls. An early decrease of MD preceded the increase of ipsilateral thalamic diffusion in one patient at the first week and in two other patients at the first month. Conclusion: After MCA infarcts, an increase in diffusion is observed with DTI in the ipsilateral thalamus later than 1 month after the stroke onset. This is presumably because of the progressive loss of neurons and/or glial cells. In some patients, this increase is preceded by a transient decrease in diffusion possibly related to an early swelling of these cells or to microglial activation. Further studies in larger series are needed to assess the clinical correlates of these findings. PMID:15654032

Malignant infarction of the middle cerebral artery in a porcine model. A pilot study

PubMed Central

Martínez-Valverde, Tamara; Sánchez-Guerrero, Ángela; Campos, Mireia; Esteves, Marielle; Gandara, Dario; Torné, Ramon; Castro, Lidia; Dalmau, Antoni; Tibau, Joan

2017-01-01

Background and purpose Interspecies variability and poor clinical translation from rodent studies indicate that large gyrencephalic animal stroke models are urgently needed. We present a proof-of-principle study describing an alternative animal model of malignant infarction of the middle cerebral artery (MCA) in the common pig and illustrate some of its potential applications. We report on metabolic patterns, ionic profile, brain partial pressure of oxygen (PtiO2), expression of sulfonylurea receptor 1 (SUR1), and the transient receptor potential melastatin 4 (TRPM4). Methods A 5-hour ischemic infarct of the MCA territory was performed in 5 2.5-to-3-month-old female hybrid pigs (Large White x Landrace) using a frontotemporal approach. The core and penumbra areas were intraoperatively monitored to determine the metabolic and ionic profiles. To determine the infarct volume, 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry analysis was performed to determine SUR1 and TRPM4 expression. Results PtiO2 monitoring showed an abrupt reduction in values close to 0 mmHg after MCA occlusion in the core area. Hourly cerebral microdialysis showed that the infarcted tissue was characterized by reduced concentrations of glucose (0.03 mM) and pyruvate (0.003 mM) and increases in lactate levels (8.87mM), lactate-pyruvate ratio (4202), glycerol levels (588 μM), and potassium concentration (27.9 mmol/L). Immunohistochemical analysis showed increased expression of SUR1-TRPM4 channels. Conclusions The aim of the present proof-of-principle study was to document the feasibility of a large animal model of malignant MCA infarction by performing transcranial occlusion of the MCA in the common pig, as an alternative to lisencephalic animals. This model may be useful for detailed studies of cerebral ischemia mechanisms and the development of neuroprotective strategies. PMID:28235044

Do patients have any special medical or rehabilitation difficulties after a craniectomy for malignant cerebral infarction during their hospitalization in a physical medicine and rehabilitation department?

PubMed

Mandon, L; Bradaï, N; Guettard, E; Bonan, I; Vahedi, K; Bousser, M G; Yelnik, A

2010-03-01

To observe whether medical complications, the evolution of neurological disorders and dependence and/or the discharge destinations are different for patients treated by craniectomy for malignant cerebral infarction in the middle cerebral artery compared to patients treated medically for severe or malignant cerebral infarction in the same cerebral territory, during their hospitalization in a physical medicine and rehabilitation department. This retrospective study compared patients treated by craniectomy for malignant cerebral infarction in the middle cerebral artery and patients treated medically for severe or malignant cerebral infarction in the same cerebral territory. Patients were paired according to age, lesion side and hospitalization period. Twelve patients treated by craniectomy (age 43+/-10.44) were paired with 12 patients treated medically (age 49+/-7.66). The two groups were comparable in terms of general undesirable medical events. The medical events related to craniectomy are described. The evolution of patient deficiencies, the length of the hospital stay (194+/-118.93 days vs 152+/-94.64 days), the Functional Independence Measure at discharge (87+/-21.28 vs 95+/-22.19) and the number of direct home discharges (7 vs 9) did not significantly differ between groups. No more medical problems were observed in the patients treated by craniectomy than in the patients treated medically, except for the medical events specifically related to craniectomy, which extended the hospital stay but had no major repercussions. 2010 Elsevier Masson SAS. All rights reserved.

The extracellular matrix in myocardial injury, repair, and remodeling

PubMed Central

2017-01-01

The cardiac extracellular matrix (ECM) not only provides mechanical support, but also transduces essential molecular signals in health and disease. Following myocardial infarction, dynamic ECM changes drive inflammation and repair. Early generation of bioactive matrix fragments activates proinflammatory signaling. The formation of a highly plastic provisional matrix facilitates leukocyte infiltration and activates infarct myofibroblasts. Deposition of matricellular proteins modulates growth factor signaling and contributes to the spatial and temporal regulation of the reparative response. Mechanical stress due to pressure and volume overload and metabolic dysfunction also induce profound changes in ECM composition that contribute to the pathogenesis of heart failure. This manuscript reviews the role of the ECM in cardiac repair and remodeling and discusses matrix-based therapies that may attenuate remodeling while promoting repair and regeneration. PMID:28459429

Cannabidiol prevents infarction via the non-CB1 cannabinoid receptor mechanism.

PubMed

Hayakawa, Kazuhide; Mishima, Kenichi; Abe, Kohji; Hasebe, Nobuyoshi; Takamatsu, Fumie; Yasuda, Hiromi; Ikeda, Tomoaki; Inui, Keiichiro; Egashira, Nobuaki; Iwasaki, Katsunori; Fujiwara, Michihiro

2004-10-25

Cannabidiol, a non-psychoactive constituent of cannabis, has been reported as a neuroprotectant. Cannabidiol and Delta(9)-tetrahydrocannabinol, the primary psychoactive constituent of cannabis, significantly decreased the infarct volume at 4 h in the mouse middle cerebral artery occlusion model. The neuroprotective effects of Delta(9)-tetrahydrocannabinol but not cannabidiol were inhibited by SR141716, a cannabinoid CB1 receptor antagonist, and were abolished by warming of the animals to the levels observed in the controls. Delta(9)-Tetrahydrocannabinol significantly decreased the rectal temperature, and the hypothermic effect was inhibited by SR141716. These results surely show that the neuroprotective effect of Delta(9)-tetrahydrocannabinol are via a CB1 receptor and temperature-dependent mechanisms whereas the neuroprotective effects of cannabidiol are independent of CB1 blockade and of hypothermia.

Lesion segmentation from multimodal MRI using random forest following ischemic stroke.

PubMed

Mitra, Jhimli; Bourgeat, Pierrick; Fripp, Jurgen; Ghose, Soumya; Rose, Stephen; Salvado, Olivier; Connelly, Alan; Campbell, Bruce; Palmer, Susan; Sharma, Gagan; Christensen, Soren; Carey, Leeanne

2014-09-01

Understanding structure-function relationships in the brain after stroke is reliant not only on the accurate anatomical delineation of the focal ischemic lesion, but also on previous infarcts, remote changes and the presence of white matter hyperintensities. The robust definition of primary stroke boundaries and secondary brain lesions will have significant impact on investigation of brain-behavior relationships and lesion volume correlations with clinical measures after stroke. Here we present an automated approach to identify chronic ischemic infarcts in addition to other white matter pathologies, that may be used to aid the development of post-stroke management strategies. Our approach uses Bayesian-Markov Random Field (MRF) classification to segment probable lesion volumes present on fluid attenuated inversion recovery (FLAIR) MRI. Thereafter, a random forest classification of the information from multimodal (T1-weighted, T2-weighted, FLAIR, and apparent diffusion coefficient (ADC)) MRI images and other context-aware features (within the probable lesion areas) was used to extract areas with high likelihood of being classified as lesions. The final segmentation of the lesion was obtained by thresholding the random forest probabilistic maps. The accuracy of the automated lesion delineation method was assessed in a total of 36 patients (24 male, 12 female, mean age: 64.57±14.23yrs) at 3months after stroke onset and compared with manually segmented lesion volumes by an expert. Accuracy assessment of the automated lesion identification method was performed using the commonly used evaluation metrics. The mean sensitivity of segmentation was measured to be 0.53±0.13 with a mean positive predictive value of 0.75±0.18. The mean lesion volume difference was observed to be 32.32%±21.643% with a high Pearson's correlation of r=0.76 (p<0.0001). The lesion overlap accuracy was measured in terms of Dice similarity coefficient with a mean of 0.60±0.12, while the contour accuracy was observed with a mean surface distance of 3.06mm±3.17mm. The results signify that our method was successful in identifying most of the lesion areas in FLAIR with a low false positive rate. Copyright © 2014 Elsevier Inc. All rights reserved.

Myocardial Infarct Segmentation from Magnetic Resonance Images for Personalized Modeling of Cardiac Electrophysiology

PubMed Central

Ukwatta, Eranga; Arevalo, Hermenegild; Li, Kristina; Yuan, Jing; Qiu, Wu; Malamas, Peter; Wu, Katherine C.

2016-01-01

Accurate representation of myocardial infarct geometry is crucial to patient-specific computational modeling of the heart in ischemic cardiomyopathy. We have developed a methodology for segmentation of left ventricular (LV) infarct from clinically acquired, two-dimensional (2D), late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) images, for personalized modeling of ventricular electrophysiology. The infarct segmentation was expressed as a continuous min-cut optimization problem, which was solved using its dual formulation, the continuous max-flow (CMF). The optimization objective comprised of a smoothness term, and a data term that quantified the similarity between image intensity histograms of segmented regions and those of a set of training images. A manual segmentation of the LV myocardium was used to initialize and constrain the developed method. The three-dimensional geometry of infarct was reconstructed from its segmentation using an implicit, shape-based interpolation method. The proposed methodology was extensively evaluated using metrics based on geometry, and outcomes of individualized electrophysiological simulations of cardiac dys(function). Several existing LV infarct segmentation approaches were implemented, and compared with the proposed method. Our results demonstrated that the CMF method was more accurate than the existing approaches in reproducing expert manual LV infarct segmentations, and in electrophysiological simulations. The infarct segmentation method we have developed and comprehensively evaluated in this study constitutes an important step in advancing clinical applications of personalized simulations of cardiac electrophysiology. PMID:26731693

Diagnosis of bowel infarction: a comparison of plain films and CT scans in 23 cases.

PubMed

Smerud, M J; Johnson, C D; Stephens, D H

1990-01-01

We retrospectively reviewed abdominal CT and plain film findings in 23 proved cases of mesenteric infarction to compare the value of the two techniques. Criteria considered specific for infarction on CT were identified in nine (39%) of 23 patients and comprised pneumatosis in seven patients (30%), mesenteric or portal venous gas in three patients (13%), and focally thick-walled bowel in two patients (9%). Criteria considered specific for bowel infarction on plain films were identified in seven (30%) of 23 patients and comprised focally edematous bowel in six patients (26%) and pneumatosis intestinalis in one patient (4%). Only one patient had specific changes on both CT and plain films, but 15 (65%) of the 23 showed specific changes on at least one study. The results indicate that plain films remain an important tool in patients suspected of mesenteric infarction and can provide information that is complementary to CT. Also, as both studies were nonspecific in eight (35%) of our patients, negative or nonspecific findings should not deter further diagnostic or interventional procedures in patients in whom the clinical suspicion of bowel infarction is high.

Long-term low dose dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in chronic heart failure in rats.

PubMed

Ahmet, Ismayil; Tae, Hyun-Jin; Lakatta, Edward G; Talan, Mark

2017-03-01

A short-term exposure to resveratrol at high dosages exerts a remarkable cardioprotective effect. Whether a long-term exposure to resveratrol at low dosages that can be obtained through consumption of a resveratrol-rich diet is beneficial to heart diseases is unknown. We tested the effects of a resveratrol-enriched diet on cardiovascular remodeling of chronic heart failure (CHF) in rats resulting from permanent ligation of left coronary artery. Two weeks after surgery, rats were started on either a resveratrol-enriched (R; 5 mg/kg per day; n = 23) or normal (Control; n = 23) diet for next 10 months. Serial echocardiography in Control showed a significant decline in LV ejection fraction, increases in LV end-systolic and end-diastolic volumes, and expansion in myocardial infarct from pre-treatment values. In R, compared with Control, there were substantial improvements in those parameters. End-point LV pressure-volume loop analysis showed a significantly improved LV systolic function and AV-coupling, an index of energy transfer efficacy between the heart and aortic tree, in R compared with Control (p < 0.05). Aortic pulse wave velocity, a measure of arterial stiffness, was significantly lower in R (389 ± 15 cm/s; p < 0.05) compared with Control (489 ± 38 cm/s). These results demonstrated that long-term dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in CHF.

Cyclosporine A at reperfusion fails to reduce infarct size in the in vivo rat heart.

PubMed

De Paulis, Damien; Chiari, Pascal; Teixeira, Geoffrey; Couture-Lepetit, Elisabeth; Abrial, Maryline; Argaud, Laurent; Gharib, Abdallah; Ovize, Michel

2013-09-01

We examined the effects on infarct size and mitochondrial function of ischemic (Isch), cyclosporine A (CsA) and isoflurane (Iso) preconditioning and postconditioning in the in vivo rat model. Anesthetized open-chest rats underwent 30 min of ischemia followed by either 120 min (protocol 1: infarct size assessment) or 15 min of reperfusion (protocol 2: assessment of mitochondrial function). All treatments administered before the 30-min ischemia (Pre-Isch, Pre-CsA, Pre-Iso) significantly reduced infarct as compared to control. In contrast, only Post-Iso significantly reduced infarct size, while Post-Isch and Post-CsA had no significant protective effect. As for the postconditioning-like interventions, the mitochondrial calcium retention capacity significantly increased only in the Post-Iso group (+58 % vs control) after succinate activation. Only Post-Iso increased state 3 (+177 and +62 %, for G/M and succinate, respectively) when compared to control. Also, Post-Iso reduced the hydrogen peroxide (H2O2) production (-46 % vs control) after complex I activation. This study suggests that isoflurane, but not cyclosporine A, can prevent lethal reperfusion injury in this in vivo rat model. This might be related to the need for a combined effect on cyclophilin D and complex I during the first minutes of reperfusion.

Does menopausal hormone therapy reduce myocardial infarction risk if initiated early after menopause? A population-based case-control study.

PubMed

Carrasquilla, Germán D; Berglund, Anita; Gigante, Bruna; Landgren, Britt-Marie; de Faire, Ulf; Hallqvist, Johan; Leander, Karin

2015-06-01

This study aims to assess whether the timing of menopausal hormone therapy initiation in relation to onset of menopause and hormone therapy duration is associated with myocardial infarction risk. This study was based on the Stockholm Heart Epidemiology Program, a population-based case-control study including 347 postmenopausal women who had experienced a nonfatal myocardial infarction and 499 female control individuals matched for age and residential area. Odds ratios (with 95% CIs) for myocardial infarction were calculated using logistic regression. Early initiation of hormone therapy (within 10 y of onset of menopause or before age 60 y), compared with never use, was associated with an odds ratio of 0.87 (95% CI, 0.58-1.30) after adjustments for lifestyle factors, body mass index, and socioeconomic status. For late initiation of hormone therapy, the corresponding odds ratio was 0.97 (95% CI, 0.53-1.76). For hormone therapy duration of 5 years or more, compared with never use, the adjusted odds ratio was 0.64 (95% CI, 0.35-1.18). For hormone therapy duration of less than 5 years, the odds ratio was 0.97 (95% CI, 0.63-1.48). Neither the timing of hormone therapy initiation nor the duration of therapy is significantly associated with myocardial infarction risk.

Cardiac and peripheral adjustments induced by early exercise training intervention were associated with autonomic improvement in infarcted rats: role in functional capacity and mortality.

PubMed

Jorge, Luciana; Rodrigues, Bruno; Rosa, Kaleizu Teodoro; Malfitano, Christiane; Loureiro, Tatiana Carolina Alba; Medeiros, Alessandra; Curi, Rui; Brum, Patricia Chakur; Lacchini, Silvia; Montano, Nicola; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2011-04-01

To test the effects of early exercise training (ET) on left ventricular (LV) and autonomic functions, haemodynamics, tissues blood flows (BFs), maximal oxygen consumption (VO(2) max), and mortality after myocardial infarction (MI) in rats. Male Wistar rats were divided into: control (C), sedentary-infarcted (SI), and trained-infarcted (TI). One week after MI, TI group underwent an ET protocol (90 days, 50-70% VO(2) max). Left ventricular function was evaluated non-invasively and invasively. Baroreflex sensitivity, heart rate variability, and pulse interval were measured. Cardiac output (CO) and regional BFs were determined using coloured microspheres. Infarcted area was reduced in TI (19 ± 6%) compared with SI (34 ± 5%) after ET. Exercise training improved the LV and autonomic functions, the CO and regional BF changes induced by MI, as well as increased SERCA2 expression and mRNA vascular endothelial growth factor levels. These changes brought about by ET resulted in mortality rate reduction in the TI (13%) group compared with the SI (54%) group. Early aerobic ET reduced cardiac and peripheral dysfunctions and preserved cardiovascular autonomic control after MI in trained rats. Consequently, these ET-induced changes resulted in improved functional capacity and survival after MI.

Fibroblast growth factor 2 is an essential cardioprotective factor in a closed‐chest model of cardiac ischemia‐reperfusion injury

PubMed Central

House, Stacey L.; Wang, Joy; Castro, Angela M.; Weinheimer, Carla; Kovacs, Attila; Ornitz, David M.

2015-01-01

Abstract Fibroblast growth factor 2 (FGF2) is cardioprotective in in vivo models of myocardial infarction; however, whether FGF2 has a protective role in in vivo ischemia‐reperfusion (IR) injury, a model that more closely mimics acute myocardial infarction in humans, is not known. To assess the cardioprotective efficacy of endogenous FGF2, mice lacking a functional Fgf2 gene (Fgf2−/−) and wild‐type controls were subjected to closed‐chest regional cardiac IR injury (90 min ischemia, 7 days reperfusion). Fgf2−/− mice had significantly increased myocardial infarct size and significantly worsened cardiac function compared to wild‐type controls at both 1 and 7 days post‐IR injury. Pathophysiological analysis showed that at 1 day after IR injury Fgf2−/− mice have worsened cardiac strain patterns and increased myocardial cell death. Furthermore, at 7 days post‐IR injury, Fgf2−/− mice showed a significantly reduced cardiac hypertrophic response, decreased cardiac vessel density, and increased vessel diameter in the peri‐infarct area compared to wild‐type controls. These data reveal both acute cardioprotective and a longer term proangiogenic potential of endogenous FGF2 in a clinically relevant, in vivo, closed‐chest regional cardiac IR injury model that mimics acute myocardial infarction. PMID:25626875

Oxygen in the Setting of Acute Myocardial Infarction: Is It Really a Breath of Fresh Air?

PubMed

Loomba, Rohit S; Nijhawan, Karan; Aggarwal, Saurabh; Arora, Rohit R

2016-03-01

Supplemental oxygen has been used in the setting of acute myocardial infarction (AMI). Once an official recommendation in the guidelines for the management of acute ST-segment elevation myocardial infarction, it is now mentioned as an intervention to be considered. Data for the use of supplemental oxygen or AMI are limited, and some data have suggested associated harm. We performed a systematic review of the literature and a subsequent meta-analysis of the data to determine the effect of high concentration oxygen versus titrated oxygen or room air in the setting of AMI. The following end points were studied: in-hospital mortality, opiate use, percentage of infarcted myocardium by magnetic resonance imaging (MRI), and mass of infarcted myocardium by MRI. No significant difference was noted with end points when comparing those randomized to high-concentration oxygen versus those randomized to titrated oxygen or room air in the setting of AMI. No significant publication bias was identified although this could not be assessed for all end points. High-concentration oxygen may not offer any benefit when compared to titrated oxygen or room air. A large, randomized trial is warranted to further delineate these differences with respect to multiple end points. © The Author(s) 2015.

K-134, a Phosphodiesterase 3 Inhibitor, Prevents Brain Damage by Inhibiting Thrombus Formation in a Rat Cerebral Infarction Model

PubMed Central

Yoshida, Hideo; Ashikawa, Yuka; Itoh, Shinsuke; Nakagawa, Takashi; Asanuma, Akimune; Tanabe, Sohei; Inoue, Yoshihiro; Hidaka, Hiroyoshi

2012-01-01

Background K-134 is a more potent antiplatelet drug with a selective inhibitory effect on phosphodiesterase 3 (PDE3) compared with its analogue, cilostazol. Objectives This study was performed to compare the ameliorating effects of K-134 and cilostazol on brain damage in an experimental photothrombotic cerebral infarction model. Methods and Results We investigated the effects of oral preadministration of PDE3 inhibitors in a rat stroke model established by photothrombotic middle cerebral artery (MCA) occlusion. K-134 significantly prolonged MCA occlusion time at doses >10 mg/kg, and reduced cerebral infarct size at 30 mg/kg in the stroke model (n = 12, 87.5±5.6 vs. 126.8±7.5 mm3, P<0.01), indicating its potent antithrombotic effect. On the other hand, the effects of cilostazol on MCA occlusion time and cerebral infarct size are relatively weak even at the high dosage of 300 mg/kg. Furthermore, K-134 blocked rat platelet aggregation more potently than cilostazol in vitro. Also in an arteriovenous shunt thrombosis model, K-134 showed an antithrombotic effect greater than cilostazol. Conclusions These findings suggest that K-134, which has strong antithrombotic activity, is a promising drug for prevention of cerebral infarction associated with platelet hyperaggregability. PMID:23110051

K-134, a phosphodiesterase 3 inhibitor, prevents brain damage by inhibiting thrombus formation in a rat cerebral infarction model.

PubMed

Yoshida, Hideo; Ashikawa, Yuka; Itoh, Shinsuke; Nakagawa, Takashi; Asanuma, Akimune; Tanabe, Sohei; Inoue, Yoshihiro; Hidaka, Hiroyoshi

2012-01-01

K-134 is a more potent antiplatelet drug with a selective inhibitory effect on phosphodiesterase 3 (PDE3) compared with its analogue, cilostazol. This study was performed to compare the ameliorating effects of K-134 and cilostazol on brain damage in an experimental photothrombotic cerebral infarction model. We investigated the effects of oral preadministration of PDE3 inhibitors in a rat stroke model established by photothrombotic middle cerebral artery (MCA) occlusion. K-134 significantly prolonged MCA occlusion time at doses >10 mg/kg, and reduced cerebral infarct size at 30 mg/kg in the stroke model (n = 12, 87.5±5.6 vs. 126.8±7.5 mm(3), P<0.01), indicating its potent antithrombotic effect. On the other hand, the effects of cilostazol on MCA occlusion time and cerebral infarct size are relatively weak even at the high dosage of 300 mg/kg. Furthermore, K-134 blocked rat platelet aggregation more potently than cilostazol in vitro. Also in an arteriovenous shunt thrombosis model, K-134 showed an antithrombotic effect greater than cilostazol. These findings suggest that K-134, which has strong antithrombotic activity, is a promising drug for prevention of cerebral infarction associated with platelet hyperaggregability.

Alteplase: a pharmacoeconomic evaluation of its use in the management of myocardial infarction.

PubMed

Barradell, L B; Goa, K L

1995-11-01

Alteplase (recombinant tissue plasminogen activator; rt-PA) is a thrombolytic agent that when given in an accelerated regimen with intravenous heparin has survival advantages compared with streptokinase in the treatment of acute myocardial infarction, as shown by the results of the Global Utilisation of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial. Although alteplase is more fibrin-specific than streptokinase, alteplase therapy is associated with a small relative increase in the incidence of haemorrhagic stroke, but appears to cause a small relative decrease in the incidence of major bleeding. Because alteplase has a higher acquisition cost than alternative thrombolytic agents, analyses have been undertaken to assess whether administration of alteplase after myocardial infarction is a cost-effective use of healthcare resources. In retrospective analyses undertaken before completion of the GUSTO trial, it was generally assumed, on the basis of better 90-minute patency rates, that alteplase would provide survival advantages compared with streptokinase or conventional nonthrombolytic therapy. Alteplase had acceptable cost-effectiveness ratios compared with conventional therapy and streptokinase therapy from both third-party payer and hospital perspectives. Subgroup analyses demonstrated that alteplase was more cost effective when given early after symptom onset and when given to patients with large infarcts. Prospective evaluations of the cost effectiveness of alteplase in 3-hour and accelerated regimens have similarly demonstrated that alteplase therapy after myocardial infarction improves survival at an 'acceptable' cost. The largest prospective evaluation undertaken to date was performed in conjunction with the GUSTO trial. Primary analysis, on the basis of the clinical findings of the GUSTO trial and prospective collection of cost data from US patients, revealed that the cost-effectiveness ratio for accelerated alteplase therapy compared with streptokinase was $US32,687 (1993 dollars) per year of life saved (YLS). This value is most relevant for US patients and lies within the definition of 'cost effective' if $US50,000/YLS is the benchmark for acceptable use of resources. The cost-effectiveness ratio for alteplase was most sensitive to assumptions regarding long term survival and cost differences after the first year following treatment. In subgroup analyses, alteplase was a cost-effective treatment option for all elderly patients (> 60 years of age) and all patients > 40 years of age with anterior infarction. Alteplase therapy appears to have in-hospital costs/charges similar to those for primary percutaneous transluminal coronary angioplasty (PTCA), mainly because PTCA appears to have a favourable effect on duration of hospitalisation. Given the technical expertise and facilities required for PTCA, it is likely that thrombolytic therapy will remain the management option of choice in most centres. In conclusion, under the conditions of the GUSTO study, accelerated alteplase in combination with intravenous heparin confers survival advantages compared with streptokinase therapy. While decision-makers must choose how best to use their available healthcare resources, pharmacoeconomic evaluations have confirmed that, on the basis of accepted benchmark values, alteplase therapy is a cost-effective therapeutic option for the treatment of acute myocardial infarction, especially in elderly patients with either anterior or inferior infarcts and nearly all patients with anterior myocardial infarction. Thus, on the basis of clinical and economic data, predominantly provided by the GUSTO trial, alteplase is a cost-effective first-line management option for acute myocardial infarction.

Effects of the methylene chloride fraction from modified Boyang-Hwan-o-Tang, a polyherbal medicine on transient middle cerebral artery occlusion-induced ischemia in rats.

PubMed

Oh, Tae Woo; Jung, Hyo Won; Shin, Gil Jo; Park, Yong-Ki

2014-01-28

To study the neuroprotective effect of the methylene chloride fraction from modified Boyang-Hwan-o-Tang (mBHT-MC), especially against neuronal apoptosis. mBHT-MC (10, 25 or 50 mg/kg) was orally administered once per day for 7 days in transient middle cerebral artery occlusion (MCAO)-induced ischemic rats. Infarction volumes was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological deficit score and the expression of apoptotic proteins such as Bcl-2, Bax and caspase-3 by Western blot in MCAO-induced ischemic brain. Neuronal apoptosis in ischemic phenumbra was also investigated by staining with hematoxylin and eosin, Nissl and Hoechst 33342. mBHT-MC administration in MCAO rats significantly decreased infarction volume and neurological deficit scores. mBHT-MC significantly enhanced Bcl-2 expression, and inhibited Bax and caspase-3 expression in ischemic brain. In addition, mBHT-MC significantly decreased the number of apoptotic neuronal cells in ischemic brains. mBHT-MC administration inhibits neuronal death induced by cerebral ischemia in rats, suggesting that mBHT-MC has a neuroprotective property in brain ischemia.

Evidence of CCR2-independent transmigration of Ly6C(hi) monocytes into the brain after permanent cerebral ischemia in mice.

PubMed

Chu, Hannah X; Kim, Hyun Ah; Lee, Seyoung; Broughton, Brad R S; Drummond, Grant R; Sobey, Christopher G

2016-04-15

Previously we showed that INCB3344, a CCR2 antagonist, inhibits transmigration of Ly6C(hi) monocytes into the brain after ischemia-reperfusion. Here we tested the effect of CCR2 inhibition during permanent cerebral ischemia. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (30 or 100mg/kg IP) 1h before middle cerebral artery occlusion and at 2 and 6h after the initiation of ischemia. After 24h, we assessed functional outcome, infarct volume and quantified immune cells in blood and brain. The increase in circulating bone marrow-derived Ly6C(hi) monocytes, but not the infiltration of those cells into the brain, was blocked by the CCR2 antagonist. INCB3344 had no effect on either neurological deficit or infarct volume. Our data confirm that cerebral ischemia triggers a CCR2-dependent increase in circulating Ly6C(hi) monocytes, but suggest that in the absence of reperfusion these cells may transmigrate into the ischemic brain in a CCR2-independent manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Pretreatment with scutellaria baicalensis stem-leaf total flavonoid prevents cerebral ischemia-reperfusion injury

PubMed Central

Zhao, Shumin; Kong, Wei; Zhang, Shufeng; Chen, Meng; Zheng, Xiaoying; Kong, Xiangyu

2013-01-01

Pretreatment with scutellaria baicalensis stem-leaf total flavonoid has protective effects against ischemia and attenuates myocardial ischemia-reperfusion injury. In this study, rats were given scutellaria baicalensis stem-leaf total flavonoid intragastrically at 50, 100, and 200 mg/kg per day for 7 days before focal cerebral ischemia-reperfusion injury models were established using the suture method. We then determined the protective effects of scutellaria baicalensis stem-leaf total flavonoid pretreatment on focal cerebral ischemia-reperfusion injury. Results showed that neurological deficit scores increased, infarct volumes enlarged, apoptosis increased and Bcl-2 and Bax protein expression were upregulated at 24 hours after reperfusion. Pretreatment with scutellaria baicalensis stem-leaf total flavonoid at any dose lowered the neurological deficit scores, reduced the infarct volume, prevented apoptosis in hippocampal cells, attenuated neuronal and blood-brain barrier damage and upregulated Bcl-2 protein expression but inhibited Bax protein expression. Doses of 100 and 200 mg/kg were the most efficacious. Our findings indicate that pretreatment with scutellaria baicalensis stem-leaf total flavonoid at 100 and 200 mg/kg can improve the neurological functions and have preventive and protective roles after focal cerebral ischemia-reperfusion injury. PMID:25206639

Neuroprotective capabilities of TSA against cerebral ischemia/reperfusion injury via PI3K/Akt signaling pathway in rats.

PubMed

Ma, Xiao-Hui; Gao, Qiang; Jia, Zhen; Zhang, Ze-Wei

2015-02-01

Hundreds of previous studies demonstrated the cytoprotective effect of trichostatin-A (TSA), a kind of histone deacetylases inhibitors (HDACIs), against cerebral ischemia/reperfusion insult. Meanwhile, phosphatidylinositol-3 kinase/Akt (PI3K/Akt) is a well-known, important signaling pathway that mediates neuroprotection. However, it should be remains unclear whether the neuroprotective capabilities of TSA against cerebral ischemia/reperfusion is mediated by activation of the PI3K/Akt signaling pathway. Five groups rats (n = 12 each), with middle cerebral artery occlusion (MCAO) except sham group, were used to investigate the neuroprotective effect of certain concentration (0.05 mg/kg) of TSA, and whether the neuroprotective effect of TSA is associated with activation of the PI3K/Akt signaling pathway through using of wortmannin (0.25 mg/kg). TSA significantly increased the expression of p-Akt protein, reduced infarct volume, and attenuated neurological deficit in rats with transient MCAO, wortmannin weakened such effect of TSA dramatically. TSA could significantly decrease the neurological deficit scores and reduce the cerebral infarct volume during cerebral ischemia/reperfusion injury, which was achieved partly by activation of the PI3K/Akt signaling pathway via upgrading of p-Akt protein.

Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.

PubMed

Jia, Jie; Zhang, Xi; Hu, Yong-Shan; Wu, Yi; Wang, Qing-Zhi; Li, Na-Na; Wu, Cai-Qin; Yu, Hui-Xian; Guo, Qing-Chuan

2009-03-01

Tetramethyl pyrazine has been considered an effective agent in treating neurons ischemia/reperfusion injury, but the mechanism of its therapeutic effect remains unclear. This study was to explore the therapeutic time window and mechanism of tetramethyl pyrazine on temporary focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg of tetramethyl pyrazine was intraperitoneally injected at different time points. At 72 h after reperfusion, all animals' neurologic deficit scores were evaluated. Cerebrums were removed and cerebral infarction volume was measured. The expression of thioredoxin and thioredoxin reductase mRNA was determined at 6 and 24 h after reperfusion. Cerebral infarction volume and neurological deficit scores were significantly decreased in the group with tetramethyl pyrazine treatment. The expression of thioredoxin-1/thioredoxin-2 and thioredoxin reductase-1/thioredoxin reductase-2 was significantly decreased in rats with ischemia/reperfusion injury, while it was increased by tetramethyl pyrazine administration. Treatment with tetramethyl pyrazine, within 4 h after reperfusion, protects the brain from ischemic reperfusion injury in rats. The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription.

[Splenic infarction at high altitude, Huaraz-Peru (3,100 masl)].

PubMed

López de Guimaraes, Douglas; Menacho López, Julio; Villanueva Palacios, Jovita; Mosquera Vásquez, Vitaliano

2009-01-01

We report three cases of splenic infarction in healthy men for the first time that amounted to high altitudes, observed in the hospital "Victor Ramos Guardia" Huaraz (3100 m). Case 1 (1995) of 55 years, born in Cuba, from Lima, caucasian suddenly presented acute abdominal pain in epigastrium, distension, nausea and vomiting, was laparotomized for acute abdomen and surgical pathology revealed thrombosis with splenic infarction splenic artery and vein. During follow-up in Lima, hemoglobin electrophoresis showed that it was heterozygous carrier of the sickle trait (Hb A: 57% Hb S: 38.5%). Case 2 (1998) of 23 years, born in Cuba, from Lima, Black said acute abdominal pain in left hypochondrium, shortness of breath and chest pain, clinical examination and radiography of the abdomen showed the spleen volume increased. Case 3 (2006) of 17 years, natural and from Lima, mestizo, who came on tour promotion, acute abdominal pain referred onset in the epigastrium and left hypochondrium, headache, increase heat, nausea and vomiting, pharyngitis was found acute and painful, and spleen increased in size by clinical and x-ray of abdomen simple stand. None had no history of hemoglobinopathy and anemia. In general, medical management was supportive and cases 2 and 3 are recommended hemoglobin electrophoresis. We conclude that we must think of splenic infarction associated with height in any healthy person who is first at high altitude (> 3000m) and having a sudden acute abdominal pain in epigastrium and / or left hypochondrium, pain and palpable spleen and radiological study compatible with image. In this case is indicated by hemoglobin electrophoresis to determine whether there is an individual heterozygous carrier of the sickle trait. splenic infarction, high altitude, sickle trait, Huaraz.

Gap in gender parity: gender disparities in incidence and clinical impact of chronic total occlusion in non-infarct artery in patients with non-ST-segment elevation myocardial infarction and multivessel coronary artery disease.

PubMed

Tajstra, Mateusz; Hawranek, Michał; Desperak, Piotr; Ciślak, Aneta; Gąsior, Mariusz

2017-10-03

A chronic total occlusion in a non-infarct-related artery is an independent predictor of mortality in non-ST elevation myocardial infarction. There are no mortality data about the impact of a chronic total occlusion in patients with non-ST elevation myocardial infarction according to gender. The purpose of this study was to evaluate the prevalence of the chronic total occlusion in in men and women and examine its impact on clinical outcomes. Data from consecutive patients with multivessel coronary artery disease treated in a high-volume center between 2006 and 2012 were included in a prospective registry and divided according to gender and the presence of chronic total occlusion. All of the analyzed patients were followed up for at least 24 months, with all-cause mortality defined as the primary endpoint. Among the 515 patients who fulfilled the inclusion criteria, 32.8% were female. In the female arm, the 24-month mortality for the groups with and without chronic total occlusion was similar (18.9% and 14.7%, respectively; p = 0.47). In contrast, in the male arm, the occurrence of chronic total occlusion was associated with higher 24-month mortality (24.3% vs. 13.4%; p = 0.009). Multivariate analysis of the male arm revealed a trend toward a positive association between the occurrence of chronic total occlusion and 24-month mortality (HR 1.62; 95% CI 0.93-2.83; p = 0.087). The presence of chronic total occlusion in men is associated with an adverse long-term prognosis, whereas in women this effect was not observed.

Segmental liver ischemia/infarction after elective transjugular intrahepatic portosystemic shunt creation: clinical outcomes in 10 patients.

PubMed

Lopera, Jorge E; Katabathina, Venkata; Bosworth, Brian; Garg, Deepak; Kroma, Ghazwan; Garza-Berlanga, Andres; Suri, Rajeev; Wholey, Michael

2015-06-01

To determine the clinical significance and potential mechanisms of segmental liver ischemia and infarction following elective creation of a transjugular intrahepatic portosystemic shunt (TIPS). A retrospective review of 374 elective TIPS creations between March 2006 and September 2014 was performed, yielding 77 contrast-enhanced scans for review. Patients with imaging evidence of segmental perfusion defects were identified. Model for End-stage Liver Disease scores, liver volume, and percentage of liver ischemia/infarct were calculated. Clinical outcomes after TIPS creation were reviewed. Ten patients showed segmental liver ischemia/infarction on contrast-enhanced imaging after elective TIPS creation. Associated imaging findings included thrombosis of the posterior division (n = 7) and anterior division (n = 3) of the right portal vein (PV). The right hepatic vein was thrombosed in 5 patients, as was the middle hepatic vein in 3 and the left hepatic vein in 1. One patient had acute thrombosis of the shunt and main PV. Three patients developed acute liver failure: 2 died within 30 days and 1 required emergent liver transplantation. One patient died of acute renal failure 20 days after TIPS creation. A large infarct in a transplant recipient resulted in biloma formation. Five patients survived without additional interventions with follow-up times ranging from 3 months to 5 years. Segmental perfusion defects are not an uncommon imaging finding after elective TIPS creation. Segmental ischemia was associated with thrombosis of major branches of the PVs and often of the hepatic veins. Clinical outcomes varied significantly, from transient problems to acute liver failure with high mortality rates. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

The Post-Myocardial Infarction Pacing Remodeling Prevention Therapy (PRomPT) Trial: Design and Rationale.

PubMed

Chung, Eugene S; Fischer, Trent M; Kueffer, Fred; Anand, Inder S; Bax, Jeroen J; Gold, Michael R; Gorman, Robert C; Theres, Heinz; Udelson, James E; Stancak, Branislav; Svendsen, Jesper H; Stone, Gregg W; Leon, Angel

2015-07-01

Despite considerable improvements in the medical management of patients with myocardial infarction (MI), patients with large MI still have substantial risk of developing heart failure. In the early post-MI setting, implantable cardioverter defibrillators have reduced arrhythmic deaths but have no impact on overall mortality. Therefore, additional interventions are required to further reduce the overall morbidity and mortality of patients with large MI. The Pacing Remodeling Prevention Therapy (PRomPT) trial is designed to study the effects of peri-infarct pacing in preventing adverse post-MI remodeling. Up to 120 subjects with peak creatine phosphokinase >3,000 U/L (or troponin T >10 μg/L) at time of MI will be randomized to either dual-site or single-site biventricular pacing with the left ventricular lead implanted in a peri-infarct region or to a nonimplanted control group. Those randomized to a device will be blinded to the pacing mode, but randomization to a device or control cannot be blinded. Subjects randomized to pacing will have the device implanted within 10 days of MI. The primary objective is to assess the change in left ventricular end-diastolic volume from baseline to 18 months. Secondary objectives are to assess changes in clinical and mechanistic parameters between the groups, including rates of hospitalization for heart failure and cardiovascular events, the incidence of sudden cardiac death and all-cause mortality, New York Heart Association functional class, 6-minute walking distance, and quality of life. The PRomPT trial will provide important evidence regarding the potential of peri-infarct pacing to interrupt adverse remodeling in patients with large MI. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical impacts of inhibition of renin-angiotensin system in patients with acute ST-segment elevation myocardial infarction who underwent successful late percutaneous coronary intervention.

PubMed

Park, Hyukjin; Kim, Hyun Kuk; Jeong, Myung Ho; Cho, Jae Yeong; Lee, Ki Hong; Sim, Doo Sun; Yoon, Nam Sik; Yoon, Hyun Ju; Hong, Young Joon; Kim, Kye Hun; Park, Hyung Wook; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Kim, Young Jo; Cho, Myeong Chan; Kim, Chong Jim

2017-01-01

Successful percutaneous coronary intervention (PCI) of the occluded infarct-related artery (IRA) in latecomers may improve long-term survival mainly by reducing left ventricular remodeling. It is not clear whether inhibition of renin-angiotensin system (RAS) brings additional better clinical outcomes in this specific population subset. Between January 2008 and June 2013, 669 latecomer patients with acute ST-segment elevation myocardial infarction (STEMI) (66.2±12.1 years, 71.0% males) in Korea Acute Myocardial Infarction Registry (KAMIR) who underwent a successful PCI were enrolled. The study population underwent a successful PCI for a totally occluded IRA. They were divided into two groups according to whether they were prescribed RAS inhibitors at the time of discharge: group I (RAS inhibition, n=556), and group II (no RAS inhibition, n=113). During the one-year follow-up, major adverse cardiac events (MACE), which consist of cardiac death and myocardial infarction, occurred in 71 patients (10.6%). There were significantly reduced incidences of MACE in the group I (hazard ratio=0.34, 95% confidence interval 0.199-0.588, p=0.001). In subgroup analyses, RAS inhibition was beneficial in patients with male gender, history of hypertension or diabetes mellitus, and even in patients with left ventricular ejection fraction (LVEF) ≥40%. In the baseline and follow-up echocardiographic data, benefit in changes of LVEF and left ventricular end-systolic volume was noted in group I. In latecomers with STEMI, RAS inhibition improved long-term clinical outcomes after a successful PCI, even in patients with low risk who had relatively preserved LVEF. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

The active metabolite of prasugrel, R-138727, improves cerebral blood flow and reduces cerebral infarction and neurologic deficits in a non-human primate model of acute ischaemic stroke.

PubMed

Sugidachi, Atsuhiro; Mizuno, Makoto; Ohno, Kousaku; Jakubowski, Joseph A; Tomizawa, Atsuyuki

2016-10-05

Previously, we showed preventive effects of prasugrel, a P2Y12 antagonist, in a non-human primate model of thrombotic middle cerebral artery occlusion (MCAO); however, it remains unclear if P2Y12 inhibition after MCAO reduces cerebral injury and dysfunction. Here we investigated the effects of R-138727, the major active metabolite of prasugrel, on ex vivo platelet aggregation at 5min, 15min, 60min, and 24h after administration to non-human primates (n=3). A single intravenous dose of R-138727 (0.03-0.3mg/kg) resulted in significant and sustained dose-related effects on platelets for up to 24h. R-138727 was administered 1h after MCAO induction, and its effects on thrombosis, cerebral infarction, and neurological deficits were determined (n=8-10). R-138727 (0.3mg/kg) significantly increased total patency rate of the MCA (P=0.0211). Although there was no effect on the patency rate before R-138727 dosing (P=0.3975), it increased 1h after dosing (P=0.0114). R-138727 significantly reduced total ischaemic infarction volumes (P=0.0147), including those of basal ganglia (P=0.0028), white matter (P=0.0393), and haemorrhagic infarction (P=0.0235). Additionally, treatment with R-138727 reduced overall neurological deficits (P=0.0019), including the subcategories of consciousness (P=0.0042), sensory system (P=0.0045), motor system (P=0.0079) and musculoskeletal coordination (P=0.0082). These findings support the possible utility of P2Y12 inhibition during early-onset MCAO to limit the progression and degree of cerebral ischaemia and infarction and also associated neurological deficits. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas.

PubMed

Riegler, Johannes; Ebert, Antje; Qin, Xulei; Shen, Qi; Wang, Mouer; Ameen, Mohamed; Kodo, Kazuki; Ong, Sang-Ging; Lee, Won Hee; Lee, Grace; Neofytou, Evgenios; Gold, Joseph D; Connolly, Andrew J; Wu, Joseph C

2016-02-09

The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm(3). A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm(3) and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Exercise training versus T3 and T4 hormones treatment: The differential benefits of thyroid hormones on the parasympathetic drive of infarcted rats.

PubMed

Teixeira, Rayane Brinck; Zimmer, Alexsandra; de Castro, Alexandre Luz; Carraro, Cristina Campos; Casali, Karina Rabello; Dias, Ingrid Gonçalves Machuca; Godoy, Alessandra Eifler Guerra; Litvin, Isnard Elman; Belló-Klein, Adriane; da Rosa Araujo, Alex Sander

2018-03-01

This study aimed to investigate whether beneficial effects of thyroid hormones are comparable to those provided by the aerobic exercise training, to verify its applicability as a therapeutic alternative to reverse the pathological cardiac remodeling post-infarction. Male rats were divided into SHAM-operated (SHAM), myocardial infarction (MI), MI subjected to exercise training (MIE), and MI who received T3 and T4 treatment (MIH) (n = 8/group). MI, MIE and MIH groups underwent an infarction surgery while SHAM was SHAM-operated. One-week post-surgery, MIE and MIH groups started the exercise training protocol (moderate intensity on treadmill), or the T3 (1.2 μg/100 g/day) and T4 (4.8 μg/100 g/day) hormones treatment by gavage, respectively, meanwhile SHAM and MI had no intervention for 9 weeks. The groups were accompanied until 74 days after surgery, when all animals were anesthetized, left ventricle echocardiography and femoral catheterization were performed, followed by euthanasia and left ventricle collection for morphological, oxidative stress, and intracellular kinases expression analysis. Thyroid hormones treatment was more effective in cardiac dilation and infarction area reduction, while exercise training provided more protection against fibrosis. Thyroid hormones treatment increased the lipoperoxidation and decreased GSHPx activity as compared to MI group, increased the t-Akt2 expression as compared to SHAM group, and increased the vascular parasympathetic drive. Thyroid hormones treatment provided differential benefits on the LV function and autonomic modulation as compared to the exercise training. Nevertheless, the redox unbalance induced by thyroid hormones highlights the importance of more studies targeting the ideal duration of this treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction]).

PubMed

Pasupathy, Sivabaskari; Tavella, Rosanna; Grover, Suchi; Raman, Betty; Procter, Nathan E K; Du, Yang Timothy; Mahadavan, Gnanadevan; Stafford, Irene; Heresztyn, Tamila; Holmes, Andrew; Zeitz, Christopher; Arstall, Margaret; Selvanayagam, Joseph; Horowitz, John D; Beltrame, John F

2017-09-05

Contemporary ST-segment-elevation myocardial infarction management involves primary percutaneous coronary intervention, with ongoing studies focusing on infarct size reduction using ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin and thus represents a potentially beneficial ancillary therapy in primary percutaneous coronary intervention. The NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction) examined the effects of NAC on infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high-dose NAC (29 g over 2 days) with background low-dose nitroglycerin (7.2 mg over 2 days) on early cardiac magnetic resonance imaging-assessed infarct size. Secondary end points included cardiac magnetic resonance-determined myocardial salvage and creatine kinase kinetics. Of 112 randomized patients with ST-segment-elevation myocardial infarction, 75 (37 in NAC group, 38 in placebo group) underwent early cardiac magnetic resonance imaging. Median duration of ischemia pretreatment was 2.4 hours. With background nitroglycerin infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in cardiac magnetic resonance-assessed infarct size relative to placebo (median, 11.0%; [interquartile range 4.1, 16.3] versus 16.5%; [interquartile range 10.7, 24.2]; P =0.02). Myocardial salvage was approximately doubled in the NAC group (60%; interquartile range, 37-79) compared with placebo (27%; interquartile range, 14-42; P <0.01) and median creatine kinase areas under the curve were 22 000 and 38 000 IU·h in the NAC and placebo groups, respectively ( P =0.08). High-dose intravenous NAC administered with low-dose intravenous nitroglycerin is associated with reduced infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes. Australian New Zealand Clinical Trials Registry. URL: http://www.anzctr.org.au/. Unique identifier: 12610000280000. © 2017 American Heart Association, Inc.

Renin-Angiotensin System Blockade Improves Cardiac Indices in Acromegaly Patients.

PubMed

Thomas, Julia D J; Dattani, Abhishek; Zemrak, Filip; Burchell, Thomas; Akker, Scott A; Kaplan, Felicity J L; Khoo, Bernard; Aylwin, Simon; Grossman, Ashley B; Davies, L Ceri; Korbonits, Márta

2017-06-01

Blockade of the angiotensin-renin system, with angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), has been shown to improve cardiac outcomes following myocardial infarction and delay progression of heart failure. Acromegaly is associated with a disease-specific cardiomyopathy, the pathogenesis of which is poorly understood.The cardiac indices of patients with active acromegaly with no hypertension (Group A, n=4), established hypertension not taking ACEi/ARBs (Group B, n=4) and established hypertension taking ACEi/ARBs (Group C, n=4) were compared using cardiac magnetic imaging.Patients taking ACEi/ARBs had lower end diastolic volume index (EDVi) and end systolic volume index (ESVi) than the other 2 groups ([C] 73.24 vs. [A] 97.92 vs. [B] 101.03 ml/m 2 , ANOVA p=0.034, B vs. C p<0.01). Groups A and B had EDVi and ESVi values at the top of published reference range values; Group C had values in the middle of the range.Acromegaly patients on ACEi/ARBs for hypertension demonstrate improved cardiac indices compared to acromegaly patients with hypertension not taking these medications. Further studies are needed to determine if these drugs have a beneficial cardiac effect in acromegaly in the absence of demonstrable hypertension. © Georg Thieme Verlag KG Stuttgart · New York.

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

PubMed

Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

2017-10-01

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p < 0.001) and higher chance of good functional outcome (OR 4.58, p < 0.001). Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p < 0.001) and lateral (+19.2%; p = 0.016) MCA territory compared to pretreatment during MCA occlusion. Safety indicators were treatment-related mortality and cardiorespiratory effects. The highest efficacy and safety profile was observed for HDT. Our findings suggest that acute modulation of cerebral collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

New angiotensin II type 1 receptor blocker, azilsartan, attenuates cardiac remodeling after myocardial infarction.

PubMed

Nakamura, Yuichi; Suzuki, Satoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

2013-01-01

After an acute myocardial infarction (MI), neurohumoral systems including renin-angiotensin-aldosterone system (RAAS) are activated which in turn aggravate cardiac remodeling. Angiotensin receptor blockers (ARBs) are useful drugs for suppression of RAAS. The purpose of this study was to evaluate a new ARB, azilsartan, for suppressing cardiac remodeling and progression to heart failure after MI. We created MI by left anterior descending coronary artery ligation in male mice, and these mice were orally administered saline (0.2 mL) in the control group (Group C), 0.1 mg/kg/d of azilsartan in the low dose group (Group L), and 1.0 mg/kg/d in the high dose group (Group H) everyday. Blood pressure was decreased in Group H, but not in Group L, compared to Group C. At 2 weeks after MI creation, infarct size and fibrotic change at the site remote to the myocardial infarcted area were attenuated in Group L and Group H compared to Group C. Echocardiography revealed that cardiac remodeling was suppressed in Group L and Group H compared to Group C. Increases of mRNA expression levels related to fibrotic change were attenuated in Group L and Group H compared to Group C. The new ARB, azilsartan, had a cardiac remodeling suppression effect after MI, and this effect was observed without blood pressure lowering.

Silymarin improves the behavioural, biochemical and histoarchitecture alterations in focal ischemic rats: a comparative evaluation with piracetam and protocatachuic acid.

PubMed

Muley, Milind M; Thakare, Vishnu N; Patil, Rajesh R; Kshirsagar, Ajay D; Naik, Suresh R

2012-08-01

Comparative neuroprotective potential of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) was evaluated in focal ischemic rats. Various pharmacological, biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite content, brain water content) and behavioural (memory impairment, motor control, neurological score) including infarct size and histopathological alterations were evaluated. Silymarin (200mg/kg) and PCA treatment significantly improved behavioural, biochemical and histopathological changes, and reduced water content and infarct size. However, piracetam only improved behavioural and histopathological changes, reduced water content and infarct size. The findings indicate that silymarin exhibits neuroprotective activity better than PCA and piracetam in focal ischemia/reperfusion reflected by its better restoration of behavioural and antioxidant profile. Copyright © 2012 Elsevier Inc. All rights reserved.

Curcumin promotes cardiac repair and ameliorates cardiac dysfunction following myocardial infarction

PubMed Central

Wang, Ning-Ping; Wang, Zhang-Feng; Tootle, Stephanie; Philip, Tiji; Zhao, Zhi-Qing

2012-01-01

BACKGROUND AND PURPOSE Curcumin, the natural yellow pigment extracted from the rhizomes of the plant curcuma longa, has been demonstrated to exhibit a variety of potent beneficial effects, acting as an antioxidant, anti-inflammatory and anti-fibrotic. In this study we tested the hypothesis that curcumin attenuates maladaptive cardiac repair and improves cardiac function after ischaemia and reperfusion by reducing degradation of extracellular matrix (ECM) and inhibiting synthesis of collagens via TGFβ/Smad-mediated signalling pathway. EXPERIMENTAL APPROACH Sprague-Dawley rats were subjected to 45 min of ischaemia followed by 7, 21 and 42 days of reperfusion respectively. Curcumin was fed orally at a dose of 150 mg·kg−1·day−1 only during reperfusion. KEY RESULTS Curcumin reduced the level of malondialdehyde, inhibited activity of MMPs, preserved ECM from degradation and attenuated collagen deposition, as it reduced the extent of collagen-rich scar and increased mass of viable myocardium. In addition to reducing collagen synthesis and fibrosis in the ischaemic/reperfused myocardium, curcumin significantly down-regulated the expression of TGFβ1 and phospho-Smad2/3, and up-regulated Smad7 and also increased the population of α-smooth muscle actin expressing myofibroblasts within the infarcted myocardium relative to the control. Echocardiography showed it significantly improved left ventricular end-diastolic volume, stroke volume and ejection fraction. The wall thickness of the infarcted middle anterior septum in the curcumin group was also greater than that in the control group. CONCLUSION AND IMPLICATIONS Dietary curcumin is effective at inhibiting maladaptive cardiac repair and preserving cardiac function after ischaemia and reperfusion. Curcumin has potential as a treatment for patients who have had a heart attack. PMID:22823335

Neuroprotective effect of hydroxy safflor yellow A against cerebral ischemia-reperfusion injury in rats: putative role of mPTP.

PubMed

Ramagiri, Sruthi; Taliyan, Rajeev

2016-01-01

Hydroxy safflor yellow A (HSYA) has been translated clinically for cardiovascular diseases. HSYA is also greatly acknowledged for its protective effects against cerebral ischemic-reperfusion (I/R) injury. Although the precise mechanism of cerebral I/R injury is not fully understood, oxygen-derived free radicals and mitochondrial permeability transition pore (mPTP) opening during I/R injury are widely recognized as an important contributor to neuronal injury. Thus, we speculated that the neuroprotective effects of HSYA against cerebral I/R injury may be associated with mPTP modulation. Induction of I/R injury was achieved by 60 min of middle cerebral artery occlusion, followed by reperfusion for 24 h. For behavior and cognitive assessment, neurological scoring (NSS), rotarod, and Y-maze task were performed. Oxidative damage was measured in terms of markers such as malondialdehyde, reduced glutathione, and catalase levels and cerebral infarct volumes were quantified using 2,3,5-triphenyl tetrazolinium chloride staining. I/R injury-induced inflammation was determined using tumor necrosis factor-α (TNF-α) levels. Animals exposed to I/R injury showed neurological severity, functional and cognitive disability, elevated oxidative markers, and TNF-α levels along with large infarct volumes. HSYA treatment during onset of reperfusion ameliorated performance in NSS, rotarod and Y-maze attenuated oxidative damage, TNF-α levels, and infarction rate. However, treatment with carboxyatractyloside, an mPTP opener, 20 min before HSYA, attenuated the protective effect of HSYA. Our study confirmed that protective effect of HSYA may be conferred through its free radical scavenger action followed by inhibiting the opening of mPTP during reperfusion and HSYA might act as a promising therapeutic agent against cerebral I/R injury.

Dabigatran Etexilate Reduces Thrombin-Induced Inflammation and Thrombus Formation in Experimental Ischemic Stroke.

PubMed

Dittmeier, Melanie; Wassmuth, Kathrin; Schuhmann, Michael K; Kraft, Peter; Kleinschnitz, Christoph; Fluri, Felix

2016-01-01

Dabigatran etexilate (DE), a direct-acting, oral inhibitor of thrombin, significantly reduces the risk of stroke compared with traditional anticoagulants, without increasing the risk of major bleeding. However, studies on the fate of cerebral tissue after ischemic stroke in patients receiving DE are sparse and the role of dabigatran-mediated reduction of thrombin in this context has not yet been investigated. Here, we investigated whether pretreatment with DE reduces thrombin-mediated pro-inflammatory mechanisms and leakage of the blood-brain barrier (BBB) following ischemic stroke in rats. Male Wistar rats received DE (15 mg/kg) or a vehicle solution 1 hour before transient middle cerebral artery occlusion (tMCAO) for 90 minutes. Infarct volume, neurologic outcome and intracranial hemorrhage (ICH) were determined after tMCAO. Thrombin generation was indirectly assessed by measuring thrombin/antithrombin III complex. Microvascular patency was evaluated histologically. Cytokine expression and immunoreactivity of cluster of differentiation (CD) 68 were examined to characterize inflammatory processes after pretreatment with DE. BBB integrity was examined by quantifying brain edema. Rats given DE revealed a significant reduction in infarct size without an increase in ICH and significant recovery of neurologic deficits compared to controls. Administration of DE decreased thrombin generation and thrombus formation, dampened the CD68-immunoreactivity and attenuated pro-inflammatory cytokine expression in the cerebral parenchyma ipsilateral to the ischemic lesion. BBB permeability was unaltered following treatment with DE. In summary, prophylactic anticoagulation with DE improves stroke outcome by reducing thrombin-induced inflammation and thrombus formation without increasing the rate of ICH.

Overall ED efficiency is associated with decreased time to percutaneous coronary intervention for ST-segment elevation myocardial infarction.

PubMed

Jones, Christopher W; Sonnad, Seema S; Augustine, James J; Reese, Charles L

2014-10-01

Performance of percutaneous coronary intervention (PCI) within 90 minutes of hospital arrival for ST-segment elevation myocardial infarction patients is a commonly cited clinical quality measure. The Centers for Medicare and Medicaid Services use this measure to adjust hospital reimbursement via the Value-Based Purchasing Program. This study investigated the relationship between hospital performance on this quality measure and emergency department (ED) operational efficiency. Hospital-level data from Centers for Medicare and Medicaid Services on PCI quality measure performance was linked to information on operational performance from 272 US EDs obtained from the Emergency Department Benchmarking Alliance annual operations survey. Standard metrics of ED size, acuity, and efficiency were compared across hospitals grouped by performance on the door-to-balloon time quality measure. Mean hospital performance on the 90-minute arrival to PCI measure was 94.0% (range, 42-100). Among hospitals failing to achieve the door-to-balloon time performance standard, median ED length of stay was 209 minutes, compared with 173 minutes among those hospitals meeting the benchmark standard (P < .001). Similarly, median time from ED patient arrival to physician evaluation was 39 minutes for hospitals below the performance standard and 23 minutes for hospitals at the benchmark standard (P < .001). Markers of ED size and acuity, including annual patient volume, admission rate, and the percentage of patients arriving via ambulance did not vary with door-to-balloon time. Better performance on measures associated with ED efficiency is associated with more timely PCI performance. Copyright © 2014 Elsevier Inc. All rights reserved.