Pseudo-acute myocardial infarction due to transient apical ventricular dysfunction syndrome (Takotsubo syndrome)

PubMed Central

Maciel, Bruno Araújo; Cidrão, Alan Alves de Lima; Sousa, Ítalo Bruno dos Santos; Ferreira, José Adailson da Silva; Messias Neto, Valdevino Pedro

2013-01-01

Takotsubo syndrome is characterized by predominantly medial-apical transient left ventricular dysfunction, which is typically triggered by physical or emotional stress. The present article reports the case of a 61-year-old female patient presenting with dizziness, excessive sweating, and sudden state of ill feeling following an episode involving intense emotional stress. The physical examination and electrocardiogram were normal upon admission, but the troponin I and creatine kinase-MB concentrations were increased. Acute myocardial infarction without ST segment elevation was suspected, and coronary angiography was immediately performed, which showed severe diffuse left ventricular hypokinesia, medial-apical systolic ballooning, and a lack of significant coronary injury. The patient was referred to the intensive care unit and was successfully treated with supportive therapy. As this case shows, Takotsubo syndrome might simulate the clinical manifestations of acute myocardial infarction, and coronary angiography is necessary to distinguish between both myocardial infarction and myocardial infarction in the acute stage. The present patient progressed with spontaneous resolution of the ventricular dysfunction without any sequelae. PMID:23887762

Erythropoietin alleviates post-resuscitation myocardial dysfunction in rats potentially through increasing the expression of angiotensin II receptor type 2 in myocardial tissues

PubMed Central

Zhou, Hourong; Huang, Jia; Zhu, Li; Cao, Yu

2018-01-01

Activation of renin-angiotensin system (RAS) is one of the pathological mechanisms associated with myocardial ischemia-reperfusion injury following resuscitation. The present study aimed to determine whether erythropoietin (EPO) improves post-resuscitation myocardial dysfunction and how it affects the renin-angiotensin system. Sprague-Dawley rats were randomly divided into sham, vehicle, epinephrine (EP), EPO and EP + EPO groups. Excluding the sham group, all groups underwent cardiopulmonary resuscitation (CPR) 4 min after asphyxia-induced cardiac arrest (CA). EP and/or EPO was administrated by intravenous injection when CPR began. The results demonstrated that the vehicle group exhibited lower mean arterial pressure, left ventricular systolic pressure, maximal ascending rate of left ventricular pressure during left ventricular isovolumic contraction and maximal descending rate of left ventricular pressure during left ventricular isovolumic relaxation (+LVdP/dt max and -LVdP/dt max, respectively), and higher left ventricular end-diastolic pressure, compared with the sham group following return of spontaneous circulation (ROSC). Few significant differences were observed concerning the myocardial function between the vehicle and EP groups; however, compared with the vehicle group, EPO reversed myocardial function indices following ROSC, excluding-LVdP/dt max. Serum renin and angiotensin (Ang) II levels were measured by ELISA. The serum levels of renin and Ang II were significantly increased in the vehicle group compared with the sham group, which was also observed for the myocardial expression of renin and Ang II receptor type 1 (AT1R), as determined by reverse transcription-quantitative polymerase chain reaction and western blotting. EPO alone did not significantly reduce the high serum levels of renin and Ang II post-resuscitation, but changed the protein levels of renin and AT1R expression in myocardial tissues. However, EPO enhanced the myocardial expression of

Facilitated ethanol metabolism promotes cardiomyocyte contractile dysfunction through autophagy in murine hearts.

PubMed

Guo, Rui; Hu, Nan; Kandadi, Machender R; Ren, Jun

2012-04-01

Chronic drinking leads to myocardial contractile dysfunction where ethanol metabolism plays an essential role. Acetaldehyde, the main ethanol metabolite, mediates alcohol-induced cell injury although the underlying mechanism is still elusive. This study was designed to examine the mechanism involved in accelerated ethanol metabolism-induced cardiac defect with a focus on autophagy. Wild-type FVB and cardiac-specific overexpression of alcohol dehydrogenase mice were placed on a 4% nutrition-balanced alcohol diet for 8 weeks. Myocardial histology, immunohistochemistry, autophagy markers and signal molecules were examined. Expression of micro RNA miR-30a, a potential target of Beclin 1, was evaluated by real-time PCR. Chronic alcohol intake led to cardiac acetaldehyde accumulation, hypertrophy and overt autophagosome accumulation (LC3-II and Atg7), the effect of which was accentuated by ADH. Signaling molecules governing autophagy initiation including class III PtdIns3K, phosphorylation of mTOR and p70S6K were enhanced and dampened, respectively, following alcohol intake. These alcohol-induced signaling responses were augmented by ADH. ADH accentuated or unmasked alcohol-induced downregulation of Bcl-2, Bcl-xL and MiR-30a. Interestingly, ADH aggravated alcohol-induced p62 accumulation. Autophagy inhibition using 3-MA abolished alcohol-induced cardiomyocyte contractile anomalies. Moreover, acetaldehyde led to cardiomyocyte contractile dysfunction and autophagy induction, which was ablated by 3-MA. Ethanol or acetaldehyde increased GFP-LC3 puncta in H9c2 cells, the effect of which was ablated by 3-MA but unaffected by lysosomal inhibition using bafilomycin A(1), E64D and pepstatin A. In summary, these data suggested that facilitated acetaldehyde production via ADH following alcohol intake triggered cardiac autophagosome formation along with impaired lysosomal degradation, en route to myocardial defect.

Phaeochromocytoma in a 86-year-old patient presenting with reversible myocardial dysfunction.

PubMed

Szwench, Elżbieta; P Czkowska, Mariola; Marczewski, Krzysztof; Klisiewicz, Anna; Micha Owska, Ilona; Ciuba, Iwona; Januszewicz, Magdalena; Prejbisz, Aleksander; Hoffman, Piotr; Januszewicz, Andrzej

2011-12-01

BACKGROUND. Phaeochromocytomas and paragangliomas are rare, mostly benign catecholamine-producing tumours of chromaffin cells of the adrenal medulla or of extra-adrenal paraganglia. Phaeochromocytoma may occur at any age, the greatest frequency being in the fourth and fifth decades. Only on extremely rare occasions does the tumour develop in the very old patients. METHODS. We are describing an 86-year-old patient with phaeochromocytoma, presenting with reversible myocardial dysfunction. RESULTS. This very old patient with phaeochromocytoma had hypertension characterized by labile blood pressure values and increased daytime blood pressure variability. This patient exhibited reversible myocardial dysfunction suggestive for "catecholaminergic cardiomyopathy", as the complication of phaeochromocytoma. After surgical removal of the tumour, recovery of left ventricular function was documented by echocardiography showing normalization of systolic function and improvement of diastolic function. CONCLUSION. Phaeochromocytomas are rare forms of secondary hypertension, but should be considered in the differential diagnosis, regardless of age, even in very old patients.

CARD9 knockout ameliorates myocardial dysfunction associated with high fat diet-induced obesity.

PubMed

Cao, Li; Qin, Xing; Peterson, Matthew R; Haller, Samantha E; Wilson, Kayla A; Hu, Nan; Lin, Xin; Nair, Sreejayan; Ren, Jun; He, Guanglong

2016-03-01

Obesity is associated with chronic inflammation which plays a critical role in the development of cardiovascular dysfunction. Because the adaptor protein caspase recruitment domain-containing protein 9 (CARD9) in macrophages regulates innate immune responses via activation of pro-inflammatory cytokines, we hypothesize that CARD9 mediates the pro-inflammatory signaling associated with obesity en route to myocardial dysfunction. C57BL/6 wild-type (WT) and CARD9(-/-) mice were fed normal diet (ND, 12% fat) or a high fat diet (HFD, 45% fat) for 5months. At the end of 5-month HFD feeding, cardiac function was evaluated using echocardiography. Cardiomyocytes were isolated and contractile properties were measured. Immunofluorescence was performed to detect macrophage infiltration in the heart. Heart tissue homogenates, plasma, and supernatants from isolated macrophages were collected to measure the concentrations of pro-inflammatory cytokines using ELISA kits. Western immunoblotting analyses were performed on heart tissue homogenates and isolated macrophages to explore the underlying signaling mechanism(s). CARD9 knockout alleviated HFD-induced insulin resistance and glucose intolerance, prevented myocardial dysfunction with preserved cardiac fractional shortening and cardiomyocyte contractile properties. CARD9 knockout also significantly decreased the number of infiltrated macrophages in the heart with reduced myocardium-, plasma-, and macrophage-derived cytokines including IL-6, IL-1β and TNFα. Finally, CARD9 knockout abrogated the increase of p38 MAPK phosphorylation, the decrease of LC3BII/LC3BI ratio and the up-regulation of p62 expression in the heart induced by HFD feeding and restored cardiac autophagy signaling. In conclusion, CARD9 knockout ameliorates myocardial dysfunction associated with HFD-induced obesity, potentially through reduction of macrophage infiltration, suppression of p38 MAPK phosphorylation, and preservation of autophagy in the heart

Estrogen receptor ERα plays a major role in ethanol-evoked myocardial oxidative stress and dysfunction in conscious female rats.

PubMed

Yao, Fanrong; Abdel-Rahman, Abdel A

2016-02-01

Our previous studies showed that ethanol elicited estrogen (E2)-dependent myocardial oxidative stress and dysfunction. In the present study we tested the hypothesis that E2 signaling via the estrogen receptor (ER), ERα, mediates this myocardial detrimental effect of alcohol. To achieve this goal, conscious female rats in proestrus phase (highest endogenous E2 level) received a selective ER antagonist (200 μg/kg; intra-venous [i.v.]) for ERα (MPP), ERβ (PHTPP) or GPER (G15) or saline 30 min before ethanol (1 g/kg; i.v.) or saline infusion. ERα blockade virtually abrogated ethanol-evoked myocardial dysfunction and hypotension, while ERβ blockade had little effect on the hypotensive response, but caused delayed attenuation of the ethanol-evoked reductions in left ventricular developed pressure and the rate of left ventricle pressure rise. GPER blockade caused delayed attenuation of all cardiovascular effects of ethanol. All three antagonists attenuated the ethanol-evoked increases in myocardial catalase and ALDH2 activities, Akt, ERK1/2, p38, eNOS, and nNOS phosphorylation, except for a lack of effect of PHTPP on p38. Finally, all three ER antagonists attenuated ethanol-evoked elevation in myocardial ROS, but this effect was most notable with ERα blockade. In conclusion, ERα plays a greater role in, and might serve as a molecular target for ameliorating, the E2-dependent myocardial oxidative stress and dysfunction caused by ethanol. Copyright © 2016 Elsevier Inc. All rights reserved.

Early detection of myocardial dysfunction using two-dimensional speckle tracking echocardiography in a young cat with hypertrophic cardiomyopathy

PubMed Central

Mochizuki, Yohei; Yoshimatsu, Hiroki; Niina, Ayaka; Teshima, Takahiro; Matsumoto, Hirotaka; Koyama, Hidekazu

2018-01-01

Case summary A 5-month-old intact female Scottish Fold cat was presented for cardiac evaluation. Careful auscultation detected a slight systolic murmur (Levine I/VI). The findings of electrocardiography, thoracic radiography, non-invasive blood pressure measurements and conventional echocardiographic studies were unremarkable. However, two-dimensional speckle tracking echocardiography revealed abnormalities in myocardial deformations, including decreased early-to-late diastolic strain rate ratios in longitudinal, radial and circumferential directions, and deteriorated segmental systolic longitudinal strain. At the follow-up examinations, the cat exhibited echocardiographic left ventricular hypertrophy and was diagnosed with hypertrophic cardiomyopathy using conventional echocardiography. Relevance and novel information This is the first report on the use of two-dimensional speckle tracking echocardiography for the early detection of myocardial dysfunction in a cat with hypertrophic cardiomyopathy; the myocardial dysfunction was detected before the development of hypertrophy. The findings from this case suggest that two-dimensional speckle tracking echocardiography can be useful for myocardial assessment when conventional echocardiographic and Doppler findings are ambiguous. PMID:29449957

Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

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

Watanabe, Tomoyuki; Saotome, Masao, E-mail: msaotome@hama-med.ac.jp; Nobuhara, Mamoru

Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}),more » they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin

History of erectile dysfunction as a predictor of poor physical performance after an acute myocardial infarction.

PubMed

Compostella, Leonida; Compostella, Caterina; Truong, Li Van Stella; Russo, Nicola; Setzu, Tiziana; Iliceto, Sabino; Bellotto, Fabio

2017-03-01

Background Erectile dysfunction may predict future cardiovascular events and indicate the severity of coronary artery disease in middle-aged men. The aim of this study was to evaluate whether erectile dysfunction (expression of generalized macro- and micro-vascular pathology) could predict reduced effort tolerance in patients after an acute myocardial infarction. Patients and methods One hundred and thirty-nine male patients (60 ± 12 years old), admitted to intensive cardiac rehabilitation 13 days after a complicated acute myocardial infarction, were evaluated for history of erectile dysfunction using the International Index of Erectile Function questionnaire. Their physical performance was assessed by means of two six-minute walk tests (performed two weeks apart) and by a symptom limited cardiopulmonary exercise test (CPET). Results Patients with erectile dysfunction (57% of cases) demonstrated poorer physical performance, significantly correlated to the degree of erectile dysfunction. After cardiac rehabilitation, they walked shorter distances at the final six-minute walk test (490 ± 119 vs. 564 ± 94 m; p < 0.001); at CPET they sustained lower workload (79 ± 28 vs. 109 ± 34 W; p < 0.001) and reached lower oxygen uptake at peak effort (18 ± 5 vs. 21 ± 5 ml/kg per min; p = 0.003) and at anaerobic threshold (13 ± 3 vs.16 ± 4 ml/kg per min; p = 0.001). The positive predictive value of presence of erectile dysfunction was 0.71 for low peak oxygen uptake (<20 ml/kg per min) and 0.69 for reduced effort capacity (W-max <100 W). Conclusions As indicators of generalized underlying vascular pathology, presence and degree of erectile dysfunction may predict the severity of deterioration of effort tolerance in post-acute myocardial infarction patients. In the attempt to reduce the possibly associated long-term risk, an optimization of type, intensity and duration of cardiac rehabilitation should be

Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats

PubMed Central

Patel, Snehal S.; Goyal, Ramesh K.

2011-01-01

Background: Normalization of hyperglycemia, hyperlipidemia, and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. Objective: This study was undertaken to examine the effects of gallic acid in myocardial dysfunctions associated with type-1 diabetes. Materials and Methods: Diabetes was induced by single intravenous injection of streptozotocin (STZ, 50 mg/kg i.v.). Gallic acid was administered daily at three different doses (100, 50, and 25 mg/kg p.o.) for 8 weeks at the end of which blood samples were collected and analyzed for various biochemical parameters. Results: Injection of STZ produced significant loss of body weight (BW), polyphagia, polydypsia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypertension, bradycardia, and myocardial functional alterations. Treatment with gallic acid significantly lowered fasting glucose, the AUCglucose level in a dose-dependent manner; however, the insulin level was not increased significantly at same the dose and prevented loss of BW, polyphagia, and polydypsia in diabetic rats. It also prevented STZ-induced hyperlipidemia, hypertension, bradycardia, structural alterations in cardiac tissue such as increase in force of contraction, left ventricular weight to body weight ratio, collagen content, protein content, serum lactate dehydrogenase, and creatinine kinase levels in a dose-dependent manner. Further, treatment also produced reduction in lipid peroxidation and increase in antioxidant parameters in heart of diabetic rats. Conclusion: The results of this study suggest that gallic acid to be beneficial for the treatment of myocardial damage associated with type-1 diabetes. PMID:22224046

Cardiac DPP-4 inhibition by saxagliptin ameliorates isoproterenol-induced myocardial remodeling and cardiac diastolic dysfunction in rats.

PubMed

Ikeda, Junichi; Kimoto, Naoya; Kitayama, Tetsuya; Kunori, Shunji

2016-09-01

Saxagliptin, a potent and selective DPP-4 inhibitor, is characterized by its slow dissociation from DPP-4 and its long half-life and is expected to have a potent tissue membrane-bound DPP-4-inhibitory effect in various tissues. In the present study, we examined the effects of saxagliptin on in situ cardiac DPP-4 activity. We also examined the effects of saxagliptin on isoproterenol-induced the changes in the early stage such as, myocardial remodeling and cardiac diastolic dysfunction. Male SD rats treated with isoproterenol (1 mg/kg/day via osmotic pump) received vehicle or saxagliptin (17.5 mg/kg via drinking water) for 2 weeks. In situ cardiac DPP-4 activity was measured by a colorimetric assay. Cardiac gene expressions were examined and an echocardiographic analysis was performed. Saxagliptin treatment significantly inhibited in situ cardiac DPP-4 activity and suppressed isoproterenol-induced myocardial remodeling and the expression of related genes without altering the blood glucose levels. Saxagliptin also significantly ameliorated cardiac diastolic dysfunction in isoproterenol-treated rats. In conclusion, the inhibition of DPP-4 activity in cardiac tissue by saxagliptin was associated with suppression of myocardial remodeling and cardiac diastolic dysfunction independently of its glucose-lowering action in isoproterenol-treated rats. Cardiac DPP-4 activity may contribute to myocardial remodeling in the development of heart failure. Copyright © 2016 Kyowa Hakko Kirin Co.,Ltd. Production and hosting by Elsevier B.V. All rights reserved.

Estrogen modulation of the ethanol-evoked myocardial oxidative stress and dysfunction via DAPK3/Akt/ERK activation in male rats

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

El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com; Abdel-Rahman, Abdel A., E-mail: abdelrahmana@ecu.edu

Evidence suggests that male rats are protected against the hypotensive and myocardial depressant effects of ethanol compared with females. We investigated whether E{sub 2} modifies the myocardial and oxidative effects of ethanol in male rats. Conscious male rats received ethanol (0.5, 1 or 1.5 g/kg i.v.) 30-min after E{sub 2} (1 μg/kg i.v.) or its vehicle (saline), and hearts were collected at the conclusion of hemodynamic measurements for ex vivo molecular studies. Ethanol had no effect in vehicle-treated rats, but it caused dose-related reductions in LV developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of rise in LV pressure (dP/dt{sub max})more » and systolic (SBP) and diastolic (DBP) blood pressures in E{sub 2}-pretreated rats. These effects were associated with elevated (i) indices of reactive oxygen species (ROS), (ii) malondialdehyde (MDA) protein adducts, and (iii) phosphorylated death-associated protein kinase-3 (DAPK3), Akt, and extracellular signal-regulated kinases (ERK1/2). Enhanced myocardial anti-oxidant enzymes (heme oxygenase-1, catalase and aldehyde dehydrogenase 2) activities were also demonstrated. In conclusion, E{sub 2} promotes ethanol-evoked myocardial oxidative stress and dysfunction in male rats. The present findings highlight the risk of developing myocardial dysfunction in men who consume alcohol while receiving E{sub 2} for specific medical conditions. - Highlights: • Ethanol lowers blood pressure and causes LV dysfunction in E{sub 2}-treated rats. • E{sub 2}/ethanol aggravates cardiac oxidative state via of DAPK3/Akt/ERK activation. • E{sub 2}/ethanol causes a feedback increase in cardiac HO-1, catalase and ALDH2. • Alcohol might increase risk of myocardial dysfunction in men treated with E{sub 2}.« less

Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

PubMed Central

Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

2015-01-01

A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

High Serum sTREM-1 Correlates With Myocardial Dysfunction and Predicts Prognosis in Septic Patients.

PubMed

Li, Zhenyu; Zhang, Enyuan; Hu, Yipeng; Liu, Yi; Chen, Bing

2016-06-01

This study aimed to evaluate the predictive and prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with myocardial dysfunction induced by severe sepsis and septic shock. A total of 84 patients with severe sepsis and septic shock were enrolled between May 2013 and December 2014.The patients were monitored by pulse indicator continuous cardiac output system and divided into myocardial depression group (cardiac function index [CFI] < 4.1/minute, n = 37) and nonmyocardial depression group (CFI ≥ 4.1/minute, n = 47 ). Additionally, the patients were divided into survival group (n = 40) and nonsurvival group (n = 44) based on 28-day mortality. Hemodynamic parameters and serum sTREM-1, B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels were collected on days 1, 3 and 5 after admission to intensive care unit. (1) The serum values of sTREM-1, BNP and cTnI in myocardial depression group were higher than those in nonmyocardial depression group (P < 0.01); and CFI, cardiac index, stroke volume, global ejection fraction and left ventricular contractility index (dpmax) in myocardial depression group were lower than those in nonmyocardial depression group on day 1 (P < 0.05); (2) serum sTREM-1 negatively correlated with left ventricular ejection fraction, CFI, cardiac index, global ejection fraction and dpmax, and it positively correlated with BNP and cTnI (P < 0.01); (3) the area under the receiver operating characteristics curve for sTREM-1 in the prediction of myocardial depression was 0.671 with a sensitivity of 83.8% and a specificity of 46.8% when cutoff point was 174.5ng/mL, the power of predicting septic depression for sTREM-1 was lower than that of BNP; logistic regression analysis showed that serum sTREM-1 was not an independent predictor of septic myocardial depression; the area under the receiver operating characteristics curve was 0.773 for sTREM-1 in predicting outcome with a sensitivity of 86

Testosterone deficiency prevents left ventricular contractility dysfunction after myocardial infarction.

PubMed

Ribeiro Júnior, R F; Ronconi, K S; Jesus, I C G; Almeida, P W M; Forechi, L; Vassallo, D V; Guatimosim, S; Stefanon, I; Fernandes, A A

2018-01-15

Testosterone may affect myocardial contractility since its deficiency decreases the contraction and relaxation of the heart. Meanwhile, testosterone replacement therapy has raised concerns because it may worsen cardiac dysfunction and remodeling after myocardial infarction (MI). In this study, we evaluate cardiac contractility 60 days after MI in rats with suppressed testosterone. Male Wistar rats underwent bilateral orchidectomy one week before the ligation of the anterior descending left coronary artery. The animals were divided into orchidectomized (OCT); MI; orchidectomized + MI (OCT + MI); orchidectomized + MI + testosterone (OCT + MI + T) and control (Sham) groups. Eight weeks after MI, papillary muscle contractility was analyzed under increasing calcium (0.62, 1.25, 2.5 and 3.75 mM) and isoproterenol (10 -8 to 10 -2  M) concentrations. Ventricular myocytes were isolated for intracellular calcium measurements and assessment of Ca 2+ handling proteins. Contractility was preserved in the orchidectomized animals after myocardial infarction and was reduced when testosterone was replaced (Ca 2+ 3.75 mM: Sham: 608 ± 70 (n = 11); OCT: 590 ± 37 (n = 16); MI: 311 ± 33* (n = 9); OCT + MI: 594 ± 76 (n = 7); OCT + MI + T: 433 ± 38* (n=4), g/g *p < 0.05 vs Sham). Orchidectomy also increased the Ca 2+ transient amplitude of the ventricular myocytes and SERCA-2a protein expression levels. PLB phosphorylation levels at Thr 17 were not different in the orchidectomized animals compared to the Sham animals but were reduced after testosterone replacement. CAMKII phosphorylation and protein nitrosylation increased in the orchidectomized animals. Our results support the view that testosterone deficiency prevents MI contractility dysfunction by altering the key proteins involved in Ca 2+ handling. Copyright © 2017 Elsevier B.V. All rights reserved.

Myocardial dysfunction occurs prior to changes in ventricular geometry in mice with chronic kidney disease (CKD).

PubMed

Winterberg, Pamela D; Jiang, Rong; Maxwell, Josh T; Wang, Bo; Wagner, Mary B

2016-03-01

Uremic cardiomyopathy is responsible for high morbidity and mortality rates among patients with chronic kidney disease (CKD), but the underlying mechanisms contributing to this complex phenotype are incompletely understood. Myocardial deformation analyses (ventricular strain) of patients with mild CKD have recently been reported to predict adverse clinical outcome. We aimed to determine if early myocardial dysfunction in a mouse model of CKD could be detected using ventricular strain analyses. CKD was induced in 5-week-old male 129X1/SvJ mice through partial nephrectomy (5/6Nx) with age-matched mice undergoing bilateral sham surgeries serving as controls. Serial transthoracic echocardiography was performed over 16 weeks following induction of CKD. Invasive hemodynamic measurements were performed at 8 weeks. Gene expression and histology was performed on hearts at 8 and 16 weeks. CKD mice developed decreased longitudinal strain (-25 ± 4.2% vs. -29 ± 2.3%; P = 0.01) and diastolic dysfunction (E/A ratio 1.2 ± 0.15 vs. 1.9 ± 0.18; P < 0.001) compared to controls as early as 2 weeks following 5/6Nx. In contrast, ventricular hypertrophy was not apparent until 4 weeks. Hearts from CKD mice developed progressive fibrosis at 8 and 16 weeks with gene signatures suggestive of evolving heart failure with elevated expression of natriuretic peptides. Uremic cardiomyopathy in this model is characterized by early myocardial dysfunction which preceded observable changes in ventricular geometry. The model ultimately resulted in myocardial fibrosis and increased expression of natriuretic peptides suggestive of progressive heart failure. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Inhibition of CYP2E1 attenuates chronic alcohol intake-induced myocardial contractile dysfunction and apoptosis.

PubMed

Zhang, Rong-Huai; Gao, Jian-Yuan; Guo, Hai-Tao; Scott, Glenda I; Eason, Anna R; Wang, Xiao-Ming; Ren, Jun

2013-01-01

Alcohol intake is associated with myocardial contractile dysfunction and apoptosis although the precise mechanism is unclear. This study was designed to examine the effect of the cytochrome P450 enzyme CYP2E1 inhibition on ethanol-induced cardiac dysfunction. Adult male mice were fed a 4% ethanol liquid or pair-fed control diet for 6weeks. Following 2weeks of diet feeding, a cohort of mice started to receive the CYP2E1 inhibitor diallyl sulfide (100mg/kg/d, i.p.) for the remaining feeding duration. Cardiac function was assessed using echocardiographic and IonOptix systems. Western blot analysis was used to evaluate CYP2E1, heme oxygenase-1 (HO-1), iNOS, the intracellular Ca(2+) regulatory proteins sarco(endo)plasmic reticulum Ca(2+)-ATPase, Na(+)Ca(2+) exchanger and phospholamban, pro-apoptotic protein cleaved caspase-3, Bax, c-Jun-NH(2)-terminal kinase (JNK) and apoptosis signal-regulating kinase (ASK-1). Ethanol led to elevated levels of CYP2E1, iNOS and phospholamban, decreased levels of HO-1 and Na(+)Ca(2+) exchanger, cardiac contractile and intracellular Ca(2+) defects, cardiac fibrosis, overt O(2)(-) production, and apoptosis accompanied with increased phosphorylation of JNK and ASK-1, the effects were significantly attenuated or ablated by diallyl sulfide. Inhibitors of JNK and ASK-1 but not HO-1 inducer or iNOS inhibitor obliterated ethanol-induced cardiomyocyte contractile dysfunction, substantiating a role for JNK and ASK-1 signaling in ethanol-induced myocardial injury. Taken together, these findings suggest that ethanol metabolism through CYP2E1 may contribute to the pathogenesis of alcoholic cardiomyopathy including myocardial contractile dysfunction, oxidative stress and apoptosis, possibly through activation of JNK and ASK-1 signaling. Copyright © 2012 Elsevier B.V. All rights reserved.

Two-dimensional color tissue Doppler imaging detects myocardial dysfunction before occurrence of hypertrophy in a young Maine Coon cat.

PubMed

Chetboul, Valerie; Sampedrano, Carolina Carlos; Gouni, Vassiliki; Nicolle, Audrey P; Pouchelon, Jean-Louis

2006-01-01

A 20-month-old healthy male Maine Coon cat was referred for a cardiovascular evaluation. Physical examination and electrocardiogram were normal. The end-diastolic subaortic interventricular septal thickness (6 mm; reference range: < or = 6mm) and the mitral flow late diastolic velocity (0.89 m/s; reference range: 0.2-0.8m/s) were within the upper ranges. However, M-mode echocardiography did not reveal any sign of hypertrophic cardiomyopathy (HCM). Tissue Doppler imaging (TDI) identified a marked left ventricular free wall dysfunction characterized by decreased myocardial velocities in early diastole, increased myocardial velocities in late diastole and the presence of postsystolic contractions both at the base and the apex for the longitudinal motion. One year later, the diagnosis of HCM was confirmed by conventional echocardiography and the cat died suddenly 2 months later. This report demonstrates for the first time in spontaneous HCM the sensitivity of TDI for early diagnosis of myocardial dysfunction and suggests that TDI should form part of the screening techniques for early diagnosis of feline HCM.

Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats

PubMed Central

Liu, Chunyan; Wang, Yangang

2017-01-01

In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive

Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats.

PubMed

Lu, Xiaofang; Wang, Yuefen; Liu, Chunyan; Wang, Yangang

2017-01-01

In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive

Endoplasmic reticulum Chaperon Tauroursodeoxycholic Acid Alleviates Obesity-Induced Myocardial Contractile Dysfunction

PubMed Central

Ceylan-Isik, Asli F.; Sreejayan, Nair; Ren, Jun

2010-01-01

ER stress is involved in the pathophysiology of obesity although little is known about the role of ER stress on obesity-associated cardiac dysfunction. This study was designed to examine the effect of ER chaperone tauroursodeoxycholic acid (TUDCA) on obesity-induced myocardial dysfunction. Adult lean and ob/ob obese mice were treated TUDCA (50 mg/kg/d, p.o.) or vehicle for 5 wks. Oral glucose tolerance test (OGTT) was performed. Echocardiography, cardiomyocyte contractile and intracellular Ca2+ properties were assessed. Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity and protein expression of intracellular Ca2+ regulatory proteins were measured using 45Ca2+ uptake and Western blot analysis, respectively. Insulin signaling, ER stress markers and HSP90 were evaluated. Our results revealed that chronic TUDCA treatment lower systolic blood pressure and lessened glucose intolerance in obese mice. Obesity led to increased diastolic diameter, cardiac hypertrophy, compromised fractional shortening, cardiomyocyte contractile (peak shortening, maximal velocity of shortening/relengthening, and duration of contraction/relaxation) and intracellular Ca2+ properties, all of which were significantly attenuated by TUDCA. TUDCA reconciled obesity-associated decreased in SERCA activity and expression, and increase in serine phosphorylation of IRS, total and phosphorylated cJun, ER stress markers Bip, peIF2α and pPERK. Obesity-induced changes in phospholamban and HSP90 were unaffected by TUDCA. In vitro finding revealed that TUDCA ablated palmitic acid-induced cardiomyocyte contractile dysfunction. In summary, these data depicted a pivotal role of ER stress in obesity-associated cardiac contractile dysfunction, suggesting the therapeutic potential of ER stress as a target in the management of cardiac dysfunction in obesity. PMID:21035453

Myofilament dysfunction contributes to impaired myocardial contraction in the infarct border zone

PubMed Central

Shimkunas, Rafael; Makwana, Om; Spaulding, Kimberly; Bazargan, Mona; Khazalpour, Michael; Takaba, Kiyoaki; Soleimani, Mehrdad; Myagmar, Bat-Erdene; Lovett, David H.; Simpson, Paul C.; Ratcliffe, Mark B.

2014-01-01

After myocardial infarction, a poorly contracting nonischemic border zone forms adjacent to the infarct. The cause of border zone dysfunction is unclear. The goal of this study was to determine the myofilament mechanisms involved in postinfarction border zone dysfunction. Two weeks after anteroapical infarction of sheep hearts, we studied in vitro isometric and isotonic contractions of demembranated myocardium from the infarct border zone and a zone remote from the infarct. Maximal force development (Fmax) of the border zone myocardium was reduced by 31 ± 2% versus the remote zone myocardium (n = 6/group, P < 0.0001). Decreased border zone Fmax was not due to a reduced content of contractile material, as assessed histologically, and from myosin content. Furthermore, decreased border zone Fmax did not involve altered cross-bridge kinetics, as assessed by muscle shortening velocity and force development kinetics. Decreased border zone Fmax was associated with decreased cross-bridge formation, as assessed from muscle stiffness in the absence of ATP where cross-bridge formation should be maximized (rigor stiffness was reduced 34 ± 6%, n = 5, P = 0.011 vs. the remote zone). Furthermore, the border zone myocardium had significantly reduced phosphorylation of myosin essential light chain (ELC; 41 ± 10%, n = 4, P < 0.05). However, for animals treated with doxycycline, an inhibitor of matrix metalloproteinases, rigor stiffness and ELC phosphorylation were not reduced in the border zone myocardium, suggesting that doxycycline had a protective effect. In conclusion, myofilament dysfunction contributes to postinfarction border zone dysfunction, myofilament dysfunction involves impaired cross-bridge formation and decreased ELC phosphorylation, and matrix metalloproteinase inhibition may be beneficial for limiting postinfarct border zone dysfunction. PMID:25128171

Evaluation of mechanical dyssynchrony and myocardial perfusion using phase analysis of gated SPECT imaging in patients with left ventricular dysfunction

PubMed Central

Trimble, Mark A.; Borges-Neto, Salvador; Honeycutt, Emily F.; Shaw, Linda K.; Pagnanelli, Robert; Chen, Ji; Iskandrian, Ami E.; Garcia, Ernest V.; Velazquez, Eric J.

2010-01-01

Background Using phase analysis of gated single photon emission computed tomography (SPECT) imaging, we examined the relation between myocardial perfusion, degree of electrical dyssynchrony, and degree of SPECT-derived mechanical dyssynchrony in patients with left ventricular (LV) dysfunction. Methods and Results We retrospectively examined 125 patients with LV dysfunction and ejection fraction of 35% or lower. Fourier analysis converts regional myocardial counts into a continuous thickening function, allowing resolution of phase of onset of myocardial thickening. The SD of LV phase distribution (phase SD) and histogram bandwidth describe LV phase dispersion as a measure of dyssynchrony. Heart failure (HF) patients with perfusion abnormalities ities have higher degrees of dyssynchrony measured by median phase SD (45.5° vs 27.7°, P < .0001) and bandwidth (117.0° vs 73.0°, P = .0006). HF patients with prolonged QRS durations have higher degrees of dyssynchrony measured by median phase SD (54.1° vs 34.7°, P < .0001) and bandwidth (136.5° vs 99.0°, P = .0005). Mild to moderate correlations exist between QRS duration and phase analysis indices of phase SD (r = 0.50) and bandwidth (r = 0.40). Mechanical dyssynchrony (phase SD >43°) was 43.2%. Conclusions HF patients with perfusion abnormalities or prolonged QRS durations QRS durations have higher degrees of mechanical dyssynchrony. Gated SPECT myocardial perfusion imaging can quantify myocardial function, perfusion, and dyssynchrony and may help in evaluating patients for cardiac resynchronization therapy. PMID:18761269

Cold stress accentuates pressure overload-induced cardiac hypertrophy and contractile dysfunction: role of TRPV1/AMPK-mediated autophagy.

PubMed

Lu, Songhe; Xu, Dezhong

2013-12-06

Severe cold exposure and pressure overload are both known to prompt oxidative stress and pathological alterations in the heart although the interplay between the two remains elusive. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated in response to a variety of exogenous and endogenous physical and chemical stimuli including heat and capsaicin. The aim of this study was to examine the impact of cold exposure on pressure overload-induced cardiac pathological changes and the mechanism involved. Adult male C57 mice were subjected to abdominal aortic constriction (AAC) prior to exposure to cold temperature (4 °C) for 4 weeks. Cardiac geometry and function, levels of TRPV1, mitochondrial, and autophagy-associated proteins including AMPK, mTOR, LC3B, and P62 were evaluated. Sustained cold stress triggered cardiac hypertrophy, compromised depressed myocardial contractile capacity including lessened fractional shortening, peak shortening, and maximal velocity of shortening/relengthening, enhanced ROS production, and mitochondrial injury, the effects of which were negated by the TRPV1 antagonist SB366791. Western blot analysis revealed upregulated TRPV1 level and AMPK phosphorylation, enhanced ratio of LC3II/LC3I, and downregulated P62 following cold exposure. Cold exposure significantly augmented AAC-induced changes in TRPV1, phosphorylation of AMPK, LC3 isoform switch, and p62, the effects of which were negated by SB366791. In summary, these data suggest that cold exposure accentuates pressure overload-induced cardiac hypertrophy and contractile defect possibly through a TRPV1 and autophagy-dependent mechanism. Copyright © 2013. Published by Elsevier Inc.

A new principle of figure-ground segregation: The accentuation.

PubMed

Pinna, Baingio; Reeves, Adam; Koenderink, Jan; van Doorn, Andrea; Deiana, Katia

2018-02-01

The problem of perceptual organization was studied by Gestalt psychologists in terms of figure-ground segregation. In this paper we explore a new principle of figure-ground segregation: accentuation. We demonstrate the effectiveness of accentuation relative to other Gestalt principles, and also consider it autonomous as it can agree with or oppose them. We consider three dynamic aspects of the principle, namely: attraction, accentuation and assignment. Each creature needs to attract, fascinate, seduce, draw attention (e.g., a mate or a prey animal) or distract, refuse, dissuade, discourage, repulse (e.g., a predator). Similarly, each organism needs to accentuate, highlight, stress, underline, emphasize or distract from another. Thus, accentuation assigns meaning to a visual pattern such as a coat, a plumage or a flower. False eyes (ocelli) and dots (diematic patterns) demonstrate "deceiving camouflage by accentuation" that confuses predators/preys and hides or highlights vital body parts (butterflies/flowers). They also display the deceiving appearance and exhibition of biological fitness. The same accents may serve different or even opposite goals. We conclude that accentuation improves the adaptive fitness of organisms in multifarious ways. Copyright © 2017 Elsevier Ltd. All rights reserved.

Decreased Autophagy Contributes to Myocardial Dysfunction in Rats Subjected to Nonlethal Mechanical Trauma

PubMed Central

Liang, Feng; Li, Xiaoyu; Wang, Li; Yang, Caihong; Yan, Zi; Zhang, Suli; Liu, Huirong

2013-01-01

Autophagy is important in cells for removing damaged organelles, such as mitochondria. Insufficient autophagy plays a critical role in tissue injury and organ dysfunction under a variety of pathological conditions. However, the role of autophagy in nonlethal traumatic cardiac damage remains unclear. The aims of the present study were to investigate whether nonlethal mechanical trauma may result in the change of cardiomyocyte autophagy, and if so, to determine whether the changed myocardial autophagy may contribute to delayed cardiac dysfunction. Male adult rats were subjected to nonlethal traumatic injury, and cardiomyocyte autophagy, cardiac mitochondrial function, and cardiac function in isolated perfused hearts were detected. Direct mechanical traumatic injury was not observed in the heart within 24 h after trauma. However, cardiomyocyte autophagy gradually decreased and reached a minimal level 6 h after trauma. Cardiac mitochondrial dysfunction was observed by cardiac radionuclide imaging 6 h after trauma, and cardiac dysfunction was observed 24 h after trauma in the isolated perfused heart. These were reversed when autophagy was induced by administration of the autophagy inducer rapamycin 30 min before trauma. Our present study demonstrated for the first time that nonlethal traumatic injury caused decreased autophagy, and decreased autophagy may contribute to post-traumatic organ dysfunction. Though our study has some limitations, it strongly suggests that cardiac damage induced by nonlethal mechanical trauma can be detected by noninvasive radionuclide imaging, and induction of autophagy may be a novel strategy for reducing posttrauma multiple organ failure. PMID:23977036

Systemic inflammation is associated with myocardial fibrosis, diastolic dysfunction, and cardiac hypertrophy in patients with hypertrophic cardiomyopathy

PubMed Central

Fang, Lu; Ellims, Andris H; Beale, Anna L; Taylor, Andrew J; Murphy, Andrew; Dart, Anthony M

2017-01-01

Background: Regional or diffuse fibrosis is an early feature of hypertrophic cardiomyopathy (HCM) and is related to poor prognosis. Previous studies have documented low-grade inflammation in HCM. The aim of this study was to examine the relationships between circulating inflammatory markers and myocardial fibrosis, systolic and diastolic dysfunction, and the degree of cardiac hypertrophy in HCM patients. Methods and results: Fifty HCM patients were recruited while 20 healthy subjects served as the control group. Seventeen inflammatory cytokines/chemokines were measured in plasma. Cardiac magnetic resonance imaging and echocardiography were used to assess cardiac phenotypes. Tumour necrosis factor (TNF)-α, interleukin (IL)-6 and serum amyloid P (SAP) were significantly increased in HCM patients compared to controls. IL-6, IL-4, and monocyte chemotactic protein (MCP)-1 were correlated with regional fibrosis while stromal cell-derived factor-1 and MCP-1 were correlated with diffuse fibrosis. Fractalkine and interferon-γ were associated with left ventricular wall thickness. The above associations remained significant in a linear regression model including age, gender, body mass index and family history. TNF-α, IL-6, SAP, MCP-1 and IL-10 were associated with parameters of diastolic dysfunction. White blood cells were also increased in HCM patients and correlated with diffuse fibrosis and diastolic dysfunction. However the associations between parameters of systemic inflammation and diastolic dysfunction were weakened in the linear regression analysis. Conclusions: Systemic inflammation is associated with parameters of the disease severity of HCM patients, particularly regional and diffuse fibrosis. Modifying inflammation may reduce myocardial fibrosis in HCM patients. PMID:29218105

Overexpression of Hsp20 Prevents Endotoxin-Induced Myocardial Dysfunction and Apoptosis via Inhibition of NF-κB Activation

PubMed Central

Wang, Xiaohong; Zingarelli, Basilia; Connor, Michael O’; Zhang, Pengyuan; Adeyemo, Adeola; Kranias, Evangelia G.; Wang, Yigang; Fan, Guo-Chang

2009-01-01

The occurrence of cardiovascular dysfunction in sepsis is associated with a significantly increased mortality rate of 70% to 90% compared with 20% in septic patients without cardiovascular impairment. Thus, rectification or blockade of myocardial depressant factors should partly ameliorate sepsis progression. Heat shock protein 20 (Hsp20) has been shown to enhance myocardial contractile function and protect against doxorubicin-induced cardiotoxicity. To investigate the possible role of Hsp20 in sepsis-mediated cardiac injury, we first examined the expression profiles of five major Hsps in response to lipopolysaccharide (LPS) challenge, and observed that only the expression of Hsp20 was downregulated in LPS-treated myocardium, suggesting that this decrease might be one of mechanisms contributing to LPS-induced cardiovascular defects. Further studies using loss-of-function and gain-of function approaches in adult rat cardiomyocytes verified that reduced Hsp20 levels were indeed correlated with the impaired contractile function. In fact, overexpression of Hsp20 significantly enhanced cardiomyocyte contractility upon LPS treatment. Moreover, after administration of LPS (25μg/g) in vivo, Hsp20 transgenic mice (10-fold overexpression) displayed: 1) an improvement in myocardial function; 2) reduced the degree of cardiac apoptosis; and 3) decreased NF-κB activity, accompanied with reduced myocardial cytokines IL-1β and TNF-α production, compared to the LPS-treated non-transgenic littermate controls. Thus, the increases in Hsp20 levels can protect against LPS-induced cardiac apoptosis and dysfunction, associated with inhibition of NF-κB activity, suggesting that Hsp20 may be a new therapeutic agent for the treatment of sepsis. PMID:19501592

Effects of statin therapy on clinical outcomes after acute myocardial infarction in patients with advanced renal dysfunction: A propensity score-matched analysis.

PubMed

Kim, Jin Sug; Kim, Weon; Park, Ji Yoon; Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyun; Moon, Ju-Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2017-01-01

Lipid lowering therapy is widely used for the prevention of cardiovascular complications after acute myocardial infarction (AMI). However, some studies show that this benefit is uncertain in patients with renal dysfunction, and the role of statins is based on the severity of renal dysfunction. In this study, we investigated the impact of statin therapy on major adverse cardiac events (MACEs) and all-cause mortality in patients with advanced renal dysfunction undergoing percutaneous coronary intervention (PCI) after AMI. This study was based on the Korea Acute Myocardial Infarction Registry database. We included 861 patients with advanced renal dysfunction from among 33,205 patients who underwent PCI after AMI between November 2005 and July 2012. Patients were divided into two groups: a statin group (n = 537) and a no-statin group (n = 324). We investigated the 12-month MACEs (cardiac death, myocardial infarction, repeated PCI or coronary artery bypass grafting) and all-cause mortality of each group. Subsequently, a propensity score-matched analysis was performed. In the total population studied, no significant differences were observed between the two groups with respect to the rate of recurrent MI, repeated PCI, coronary artery bypass grafting (CABG), or all-cause mortality. However, the cardiac death rate was significantly lower in the statin group (p = 0.009). Propensity score-matched analysis yielded 274 pairs demonstrating, results similar to those obtained from the total population. However, there was no significant difference in the cardiac death rate in the propensity score-matched population (p = 0.103). Cox-regression analysis revealed only left ventricular ejection fraction to be an independent predictor of 12-month MACEs (Hazard ratio [HR] of 0.979, 95% confidence interval [CI], 0962-0.996, p = 0.018). Statin therapy was not significantly associated with a reduction in the 12-month MACEs or all-cause mortality in patients with advanced renal dysfunction

Lin28a protects against postinfarction myocardial remodeling and dysfunction through Sirt1 activation and autophagy enhancement.

PubMed

Hao, Yuanyuan; Lu, Qun; Yang, Guodong; Ma, Aiqun

2016-10-28

Myocardial remodeling and cardiac dysfunction prevention may represent a therapeutic approach to reduce mortality in patients with myocardial infarction (MI). We investigated the effects of Lin28a in experimental MI models, as well as the mechanisms underlying these effects. Left anterior descending (LAD) coronary artery ligation was used to construct an MI-induced injury model. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of Lin28a against MI-induced injury. Lin28a significantly inhibited left ventricular remodeling and cardiac dysfunction after MI, as demonstrated via echocardiography and hemodynamic measurements. Lin28a reduced cardiac enzyme and inflammatory marker release in mice subjected to MI-induced injury. The mechanisms underlying the protective effects of Lin28a against MI-induced injury were associated with autophagy enhancements and apoptosis inhibition. Consistent with these findings, Lin28a knockdown aggravated cardiac remodeling and dysfunction after MI-induced injury. Lin28a knockdown also inhibited cardiomyocyte autophagy and increased cardiomyocyte apoptosis in mice subjected to MI-induced injury. Interestingly, Sirt1 knockdown abolished the protective effects of Lin28a against cardiac remodeling and dysfunction after MI, and Lin28a failed to increase the numbers of GFP-LC3-positive punctae and decrease aggresome and p62 accumulation in Sirt1-knockdown neonatal cardiomyocytes subjected to hypoxia-induced injury. Lin28a inhibits cardiac remodeling, improves cardiac function, and reduces cardiac enzyme and inflammatory marker release after MI. Lin28a also up-regulates cardiomyocyte autophagy and inhibits cardiomyocyte apoptosis through Sirt1 activation. Copyright © 2016 Elsevier Inc. All rights reserved.

Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity.

PubMed

Li, Wei; Tang, Renqiao; Ouyang, Shengrong; Ma, Feifei; Liu, Zhuo; Wu, Jianxin

2017-01-01

Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status. HFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment. FA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

Attenuating the defibrillation dosage decreases postresuscitation myocardial dysfunction in a swine model of pediatric ventricular fibrillation

PubMed Central

Berg, Marc D.; Banville, Isabelle L.; Chapman, Fred W.; Walker, Robert G.; Gaballa, Mohammed A.; Hilwig, Ronald W.; Samson, Ricardo A.; Kern, Karl B.; Berg, Robert A.

2009-01-01

Objective The optimal biphasic defibrillation dose for children is unknown. Postresuscitation myocardial dysfunction is common and may be worsened by higher defibrillation doses. Adult-dose automated external defibrillators are commonly available; pediatric doses can be delivered by attenuating the adult defibrillation dose through a pediatric pads/cable system. The objective was to investigate whether unattenuated (adult) dose biphasic defibrillation results in greater postresuscitation myocardial dysfunction and damage than attenuated (pediatric) defibrillation. Design Laboratory animal experiment. Setting University animal laboratory. Subjects Domestic swine weighing 19 ± 3.6 kg. Interventions Fifty-two piglets were randomized to receive biphasic defibrillation using either adult-dose shocks of 200, 300, and 360 J or pediatric-dose shocks of ~50, 75, and 85 J after 7 mins of untreated ventricular fibrillation. Contrast left ventriculograms were obtained at baseline and then at 1, 2, 3, and 4 hrs postresuscitation. Postresuscitation left ventricular ejection fraction and cardiac troponins were evaluated. Measurements and Main Results By design, piglets in the adult-dose group received shocks with more energy (261 ± 65 J vs. 72 ± 12 J, p < .001) and higher peak current (37 ± 8 A vs. 13 ± 2 A, p < .001) at the largest defibrillation dose needed. In both groups, left ventricular ejection fraction was reduced significantly at 1, 2, and 4 hrs from baseline and improved during the 4 hrs postresuscitation. The decrease in left ventricular ejection fraction from baseline was greater after adult-dose defibrillation. Plasma cardiac troponin levels were elevated 4 hrs postresuscitation in 11 of 19 adult-dose piglets vs. four of 20 pediatric-dose piglets (p = .02). Conclusions Unattenuated adult-dose defibrillation results in a greater frequency of myocardial damage and worse postresuscitation myocardial function than pediatric doses in a swine model of prolonged out

Cardiac macrophages promote diastolic dysfunction.

PubMed

Hulsmans, Maarten; Sager, Hendrik B; Roh, Jason D; Valero-Muñoz, María; Houstis, Nicholas E; Iwamoto, Yoshiko; Sun, Yuan; Wilson, Richard M; Wojtkiewicz, Gregory; Tricot, Benoit; Osborne, Michael T; Hung, Judy; Vinegoni, Claudio; Naxerova, Kamila; Sosnovik, David E; Zile, Michael R; Bradshaw, Amy D; Liao, Ronglih; Tawakol, Ahmed; Weissleder, Ralph; Rosenzweig, Anthony; Swirski, Filip K; Sam, Flora; Nahrendorf, Matthias

2018-02-05

Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging and heart failure with preserved ejection fraction, remain unclear. Here we show that cardiac macrophages expand in humans and mice with diastolic dysfunction, which in mice was induced by either hypertension or advanced age. A higher murine myocardial macrophage density results from monocyte recruitment and increased hematopoiesis in bone marrow and spleen. In humans, we observed a parallel constellation of hematopoietic activation: circulating myeloid cells are more frequent, and splenic 18 F-FDG PET/CT imaging signal correlates with echocardiographic indices of diastolic dysfunction. While diastolic dysfunction develops, cardiac macrophages produce IL-10, activate fibroblasts, and stimulate collagen deposition, leading to impaired myocardial relaxation and increased myocardial stiffness. Deletion of IL-10 in macrophages improves diastolic function. These data imply expansion and phenotypic changes of cardiac macrophages as therapeutic targets for cardiac fibrosis leading to diastolic dysfunction. © 2018 Hulsmans et al.

Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension

PubMed Central

Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M. Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A.C.

2016-01-01

Background— The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. Methods and Results— By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. Conclusions— RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. PMID:27370069

Overweight female rats selectively breed for low aerobic capacity exhibit increased myocardial fibrosis and diastolic dysfunction

PubMed Central

Johnson, Megan S.; Ma, Lixin; Pulakat, Lakshmi; Mugerfeld, Irina; Hayden, Melvin R.; Garro, Mona; Knight, William; Britton, Steven L.; Koch, Lauren G.; Sowers, James R.

2012-01-01

The statistical association between endurance exercise capacity and cardiovascular disease suggests that impaired aerobic metabolism underlies the cardiovascular disease risk in men and women. To explore this connection, we applied divergent artificial selection in rats to develop low-capacity runner (LCR) and high-capacity runner (HCR) rats and found that disease risks segregated strongly with low running capacity. Here, we tested if inborn low aerobic capacity promotes differential sex-related cardiovascular effects. Compared with HCR males (HCR-M), LCR males (LCR-M) were overweight by 34% and had heavier retroperitoneal, epididymal, and omental fat pads; LCR females (LCR-F) were 20% heavier than HCR females (HCR-F), and their retroperitoneal, but not perireproductive or omental, fat pads were heavier as well. Unlike HCR-M, blood pressure was elevated in LCR-M, and this was accompanied by left ventricular (LV) hypertrophy. Like HCR-F, LCR-F exhibited normal blood pressure and LV weight as well as increased spontaneous cage activity compared with males. Despite normal blood pressures, LCR-F exhibited increased myocardial interstitial fibrosis and diastolic dysfunction, as indicated by increased LV stiffness, a decrease in the initial filling rate, and an increase in diastolic relaxation time. Although females exhibited increased arterial stiffness, ejection fraction was normal. Increased interstitial fibrosis and diastolic dysfunction in LCR-F was accompanied by the lowest protein levels of phosphorylated AMP-actived protein kinase [phospho-AMPK (Thr172)] and silent information regulator 1. Thus, the combination of risk factors, including female sex, intrinsic low aerobic capacity, and overweightness, promote myocardial stiffness/fibrosis sufficient to induce diastolic dysfunction in the absence of hypertension and LV hypertrophy. PMID:22345570

Prevalence of arterial stiffness and the risk of myocardial diastolic dysfunction in women.

PubMed

Seeland, Ute; Brecht, Anna; Nauman, Ahmad T; Oertelt-Prigione, Sabine; Ruecke, Mirjam; Knebel, Fabian; Stangl, Verena; Regitz-Zagrosek, Vera

2016-10-01

The present study determines the prevalence of vascular dysfunction and arterial stiffness (ASt) in a female urban population by measuring the brachial augmentation index (AIx) and aortic pulse wave velocity (PWV). The study tests the hypothesis that the measurement of AIx and PWV is useful in addition to that of traditional cardiovascular risk factors when assessing the risk for left ventricular diastolic dysfunction (LVDD). This cross-sectional study recruited 965 women aged 25-75 years from 12 districts of Berlin. The ASt indices, brachial AIx, aortic PWV and the central blood pressure were measured by an oscillometric method. A randomly selected subgroup (n=343) was examined by echocardiography. Trans-mitral inflow E/A ratio and diastolic mitral annulus velocity (é) were assessed. Questionnaires, medical history and blood sampling were used for the evaluation of individual risk factors. Normal vascular function was found in 55% of the women included. The prevalence of women with pathological AIx only (AIx ⩾ -10%, PWV normal) was 21.5%, whereas 17.9% were affected by increased AIx and PWV (AIx ⩾ -10%, PWV ⩾9.7 m/s), and 6% with only pathological PWV values. The prevalence of LVDD was 31.7%. LVDD was significantly associated with pathological PWV ⩾ 9.7 m/s [OR: 1.27, 95%CI: 1.02-1.57], age [OR: 4.17, 95%CI: 2.87-6.07] and a waist circumference >80 cm [OR: 3.61, 95%CI: 1.85-7.04] in multiple regression analysis. The high prevalence of markers for vascular dysfunction and ASt in a general female population and their importance as a mediator of diastolic dysfunction should encourage implementation of aortic PWV measurement to improve cardiovascular-risk assessment in particular to identify subclinical myocardial diastolic dysfunction. © 2016 The Author(s).

Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial.

PubMed

Hadadzadeh, Mehdi; Hosseini, Seyed Habib; Mostafavi Pour Manshadi, Seyed Mohammad Yousof; Naderi, Nafiseh; Emami Meybodi, Mahmood

2013-01-01

Myocardial dysfunction is a major complication in cardiac surgery that needs inotropic support. This study evaluates the effect of milrinone on patients with low ventricular ejection fraction undergoing off- pump coronary artery bypass graft (OPCAB). The present study is designed to evaluate the effect of milrinone on myocardial dysfunction. Eighty patients with low ventricular ejection fraction (<35%), candidate for elective OPCAB, were enrolled in this study. They were randomly assigned to two groups. One group received milrinone (50 μg/kg) intravenously and another group received a saline as placebo followed by 24 hours infusion of each agent (0.5 μg/kg/min). Short outcome of patients such as hemodynamic parameters and left ventricular ejection fraction were variables evaluated. Serum levels of creatine phosphokinase, the MB isoenzyme of creatine kinase, occurrence of arrhythmias and mean duration of mechanical ventilation were significantly lower in milrinone group (P<0.05). The mean post operative left ventricular ejection fraction was significantly higher in milrinone group (P=0.031). There were no statistical significant differences between the two groups in terms of intra-aortic balloon pump, inotropic support requirement, myocardial ischemia, myocardial infarction, duration of inotropic support, duration of intensive care unit stay, mortality and morbidity rate. Administration of milrinone in patients undergoing OPCAB with low ventricular ejection fraction is useful and effective.

Pyridostigmine prevents peripheral vascular endothelial dysfunction in rats with myocardial infarction.

PubMed

Qin, Fangfang; Lu, Yi; He, Xi; Zhao, Ming; Bi, Xueyuan; Yu, Xiaojiang; Liu, Jinjun; Zang, Weijin

2014-03-01

1. Myocardial infarction (MI) is characterized by the withdrawal of vagal activity and increased sympathetic activity. We have shown previously that pyridostigmine (PYR), an acetylcholinesterase inhibitor, was able to improve vagal activity and ameliorate cardiac dysfunction following MI. However, the effect of PYR on endothelial dysfunction in peripheral arteries after MI remains unclear. 2. In the present study, MI was induced by coronary artery ligation in adult Sprague-Dawley rats. Rats were treated intragastrically with saline or PYR (approximately 31 mg/kg per day) for 2 weeks, at which time haemodynamic and parasympathetic parameters and the vascular reactivity of isolated mesenteric arteries were measured and the ultrastructure of the endothelium evaluated. 3. Compared with the MI group, PYR not only improved cardiac function, vagal nerve activity and endothelial impairment, but also reduced intravascular superoxide anion and malondialdehyde. In addition, in the PYR-treated MI group, nitric oxide (NO) bioavailability was increased and attenuated endothelium-dependent relaxations were improved, whereas restored vasodilator responses were inhibited by N(G)-nitro-L-arginine methyl ester. 4. Based on our results, PYR is able to attenuate the impairment of peripheral endothelial function and maintain endothelial ultrastructural integrity in MI rats by inhibiting reactive oxygen species production, enhancing NO bioavailability and improving vagal activity. © 2014 Wiley Publishing Asia Pty Ltd.

Assessment of subclinical right ventricular systolic dysfunction in coal miners using myocardial isovolumic acceleration.

PubMed

Ozcan Abacıoglu, Ozge; Kaplan, Mehmet; Abacıoglu, Serkan; Quisi, Ala

2017-09-01

Several studies have been conducted regarding the effects of coal mining on the respiratory system. However, there is a lack of data concerning potential effects of coal mining on the cardiovascular system. In this study, we aimed to evaluate the potential subclinical right and left ventricular dysfunction in coal miners. This single-center, prospective study included a total of 102 patients. Patient and control groups consisted of 54 coal miners and 48 healthy men, respectively. All patients underwent 12-lead electrocardiography, transthoracic echocardiography, and pulmonary function test. As compared to control group, coal miners had significantly higher right ventricular myocardial performance index (RVMPI) (0.41 ± 0.03 vs 0.37 ± 0.02, P < .001), lower right ventricular fractional area change (RVFAC) (33.55% ± 6.70% vs 37.04 ± 9.26 P < .05), lower tricuspid annular plane systolic excursion (TAPSE) (1.54 ± 0.17 vs 1.73 ± 0.25, P < .001), lower myocardial isovolumic acceleration (IVA) (2.13 ± 0.16 vs 2.56 ± 0.36 P < .001) and decreased aortic distensibility (AD) (4.14 ± 2.18 vs 6.63 ± 3.91 P < .001). All of the echocardiographic parameters were positively correlated with exposure time to coal mine dust, except IVA. Echocardiographic parameters of both right and left ventricular dysfunction, including RVMPI, RVFAC, TAPSE, IVA, and AD, are impaired in coal miners. © 2017 The Authors Echocardiography Published by Wiley Periodicals, Inc.

Estrogen Receptors α and β Play Major Roles in Ethanol-Evoked Myocardial Oxidative Stress and Dysfunction in Conscious Ovariectomized Rats.

PubMed

Yao, Fanrong; Abdel-Rahman, Abdel A

2017-02-01

We documented the dependence of ethanol (EtOH)-evoked myocardial dysfunction on estrogen (E 2 ), and our recent estrogen receptor (ER) blockade study, in proestrus rats, implicated ERα signaling in this phenomenon. However, a limitation of selective pharmacological loss-of-function approach is the potential contribution of the other 2 ERs to the observed effects because crosstalk exists between the 3 ERs. Here, we adopted a "regain"-of-function approach (using selective ER subtype agonists) to identify the ER subtype(s) required for unraveling the E 2 -dependent myocardial oxidative stress/dysfunction caused by EtOH in conscious ovariectomized (OVX) rats. OVX rats received a selective ERα (PPT), ERβ (DPN), or GPER (G1) agonist (10 μg/kg; i.v.) or vehicle 30 minutes before EtOH (1.0 g/kg; infused i.v. over 30 minutes) or saline, and the hemodynamic recording continued for additional 60 minutes. Thereafter, left ventricular tissue was collected for conducting ex vivo molecular/biochemical studies. EtOH had no hemodynamic effects in OVX rats, but reduced the left ventricular contractility index, dP/dt max , and MAP after acute ERα (PPT) or ERβ (DPN) activation. These responses were associated with increases in the phosphorylation of ERK1/2 and eNOS, and in reactive oxygen species (ROS) and malondialdehyde (MDA) levels in the myocardium. GPER activation (G1) only unraveled a modest EtOH-evoked hypotension and elevation in myocardial ROS. PPT enhanced catalase, DPN reduced ALDH2, while G1 had no effect on the activity of either enzyme, and none of the agonists influenced alcohol dehydrogenase or CYP2E1 activities in the myocardium. Blood EtOH concentration (96.0 mg/dl) was significantly reduced following ERα (59.8 mg/dl) or ERβ (62.9 mg/dl), but not GPER (100.3 mg/dl), activation in EtOH-treated OVX rats. ERα and ERβ play major roles in the E 2 -dependent myocardial dysfunction caused by EtOH by promoting combined accumulation of cardiotoxic (ROS and

Protective effects of combination of quercetin and α-tocopherol on mitochondrial dysfunction and myocardial infarct size in isoproterenol-treated myocardial infarcted rats: biochemical, transmission electron microscopic, and macroscopic enzyme mapping evidences.

PubMed

Punithavathi, V R; Stanely Mainzen Prince, P

2010-01-01

Mitochondrial dysfunction plays an important role in the pathology of myocardial infarction. We evaluated the combined protective effects of quercetin and α-tocopherol on mitochondrial damage and myocardial infarct size in isoproterenol-induced myocardia- infarcted rats. Rats were pretreated with quercetin (10 mg/kg) alone, α-tocopherol (10 mg/kg) alone, and combination of quercetin (10 mg/kg) and α-tocopherol (10 mg/kg) orally using an intragastric tube daily for 14 days. After pretreatment, rats were induced myocardial infarction by isoproterenol (100 mg/kg) at an interval of 24 h for 2 days. Isoproterenol treatment caused significant increase in mitochondrial lipid peroxides with significant decrease in mitochondrial antioxidants. Significant decrease in the activities of isocitrate, succinate, malate, and α-ketoglutarate and NADH dehydrogenases and cytochrome-c-oxidase, significant increase in calcium, and significant decrease in adenosine triphosphate were observed in mitochondria of myocardial infarcted rats. Combined pretreatment with quercetin and α-tocopherol normalized all the biochemical parameters and preserved the integrity of heart tissue and restored normal mitochondrial function in myocardial-infarcted rats. Transmission electron microscopic findings on heart mitochondria and macroscopic enzyme mapping assay on the size of myocardial infarct also correlated with these biochemical parameters. The present study showed that combined pretreatment was highly effective than single pretreatment. Copyright 2010 Wiley Periodicals, Inc.

[Renal dysfunction in patients with myocardial infarction concurrent with type 2 diabetes mellitus].

PubMed

Evseeva, M V; Karetnikova, V N; Barbarash, O L

2015-01-01

Carbohydrate metabolic disturbances are an independent risk factor for not only the development, but also poor course of cardiovascular diseases, particularly those concurrent with renal dysfunction (RD). This factor acquires particular relevance due to the fact that the incidence of type 2 diabetes mellitus significantly continues to rise worldwide. The review considers the main mechanisms and common components of the pathogenesis of RD, as well as the constituents forming its basis in the presence of carbohydrate metabolic disturbances. Moreover, it highlights the timely detection of RD, a search for new biomarkers of prognostic value for cardiovascular events, and the early diagnosis of RD. The review unveils the present view of optimal diagnostic and management tactics for patients with myocardial infarction concurrent with background diseases.

Can We Rule Out Meningitis from Negative Jolt Accentuation? A Retrospective Cohort Study.

PubMed

Sato, Ryota; Kuriyama, Akira; Luthe, Sarah Kyuragi

2017-04-01

Jolt accentuation has been considered to be the most sensitive physical finding to predict meningitis. However, there are only a few studies assessing the diagnostic accuracy of jolt accentuation. Therefore, we aimed to evaluate the diagnostic accuracy of jolt accentuation and investigate whether it can be extended to patients with mild altered mental status. We performed a single center, retrospective observational study on patients who presented to the emergency department in a Japanese tertiary care center from January 1, 2010 to March 31, 2016. Jolt accentuation evaluated in patients with fever, headache, and mild altered mental status with Glasgow Coma Scale no lower than E2 or M4 was defined as "jolt accentuation in the broad sense." Jolt accentuation evaluated in patients with fever, headache, and no altered mental status was defined as "jolt accentuation in the narrow sense." We evaluated the sensitivity and specificity in both groups. Among 118 patients, the sensitivity and specificity of jolt accentuation in the broad sense were 70.7% (95% confidence interval (CI): 58.0%-80.8%) and 36.7% (95% CI: 25.6%-49.3%). The positive likelihood ratio and negative likelihood ratio were 1.12 (95% CI: 0.87-1.44) and 0.80 (95% CI: 0.48-1.34), respectively. Among 108 patients, the sensitivity and specificity of jot accentuation in the narrow sense were 75.0% (95% CI: 61.8%-84.8%) and 35.1% (95% CI: 24.0%-48.0%). The positive likelihood ratio and negative likelihood ratio were 1.16 (95% CI: 0.90-1.48) and 0.71 (95% CI: 0.40-1.28), respectively. Jolt accentuation itself has a limited value in the diagnosis of meningitis regardless of altered mental status. Therefore, meningitis should not be ruled out by negative jolt accentuation. © 2017 American Headache Society.

Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

PubMed

Pfeffer, Marc A; McMurray, John J V; Velazquez, Eric J; Rouleau, Jean-Lucien; Køber, Lars; Maggioni, Aldo P; Solomon, Scott D; Swedberg, Karl; Van de Werf, Frans; White, Harvey; Leimberger, Jeffrey D; Henis, Marc; Edwards, Susan; Zelenkofske, Steven; Sellers, Mary Ann; Califf, Robert M

2003-11-13

Angiotensin-converting-enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double-blind trial, we compared the effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combination of the two on mortality in this population of patients. Patients receiving conventional therapy were randomly assigned, 0.5 to 10 days after acute myocardial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. During a median follow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98; hazard ratio in the valsartan-and-captopril group as compared with the captopril group, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality (P=0.004) and with regard to the composite end point of fatal and nonfatal cardiovascular events (P<0.001). The valsartan-and-captopril group had the most drug-related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group. Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival. Copyright 2003

Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction.

PubMed

Li, Longhu; Haider, Husnain Kh; Wang, Linlin; Lu, Gang; Ashraf, Muhammad

2012-05-15

We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction.

IGF-1 Alleviates High Fat Diet-Induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function

PubMed Central

Zhang, Yingmei; Yuan, Ming; Bradley, Katherine M.; Dong, Feng; Anversa, Piero; Ren, Jun

2012-01-01

Obesity is often associated with reduced plasma IGF-1 levels, oxidative stress, mitochondrial damage and cardiac dysfunction. This study was designed to evaluate the impact of IGF-1 on high fat diet-induced oxidative, myocardial, geometric and mitochondrial responses. FVB and cardiomyocyte-specific IGF-1 overexpression transgenic mice were fed a low (10%) or high fat (45%) diet to induce obesity. High fat diet feeding led to glucose intolerance, elevated plasma levels of leptin, interleukin-6, insulin and triglyceride as well as reduced circulating IGF-1 levels. Echocardiography revealed reduced fractional shortening, increased end systolic and diastolic diameter, increased wall thickness, and cardiac hypertrophy in high fat-fed FVB mice. High fat diet promoted ROS generation, apoptosis, protein and mitochondrial damage, reduced ATP content, cardiomyocyte cross-sectional area, contractile and intracellular Ca2+ dysregulation, including depressed peak shortening and maximal velocity of shortening/relengthening, prolonged duration of relengthening, and dampened intracellular Ca2+ rise and clearance. Western blot analysis revealed disrupted phosphorylation of insulin receptor, post-receptor signaling molecules IRS-1 (tyrosine/serine phosphorylation), Akt, GSK3β, Foxo3a, mTOR, as well as downregulated expression of mitochondrial proteins PPARγ coactivator 1α (PGC1α) and UCP-2. Intriguingly, IGF-1 mitigated high fat diet feeding-induced alterations in ROS, protein and mitochondrial damage, ATP content, apoptosis, myocardial contraction, intracellular Ca2+ handling and insulin signaling, but not whole body glucose intolerance and cardiac hypertrophy. Exogenous IGF-1 treatment also alleviated high fat diet-induced cardiac dysfunction. Our data revealed that IGF-1 alleviates high fat diet-induced cardiac dysfunction despite persistent cardiac remodeling, possibly due to preserved cell survival, mitochondrial function and insulin signaling. PMID:22275536

Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction

PubMed Central

Li, Longhu; Haider, Husnain Kh.; Wang, Linlin; Lu, Gang

2012-01-01

We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction. PMID:22447941

Tissue Doppler imaging for detection of radial and longitudinal myocardial dysfunction in a family of cats affected by dystrophin-deficient hypertrophic muscular dystrophy.

PubMed

Chetboul, Valérie; Blot, Stephane; Sampedrano, Carolina Carlos; Thibaud, Jean-Laurent; Granger, Nicolas; Tissier, Renaud; Bruneval, Patrick; Gaschen, Frederic; Gouni, Vassiliki; Nicolle, Audrey P; Pouchelon, Jean-Louis

2006-01-01

Diagnosis of feline hypertrophic cardiomyopathy currently is based on the presence of myocardial hypertrophy detected using conventional echocardiography. The accuracy of tissue Doppler imaging (TDI) for earlier detection of the disease has never been described. The objective of this sudy was to quantify left ventricular free wall (LVFW) velocities in cats with hypertrophic muscular dystrophy (HFMD) during preclinical cardiomyopathy using TDI. The study animals included 22 healthy controls and 7 cats belonging to a family of cats with HFMD (2 affected adult males, 2 heterozygous adult females, one 2.5-month-old affected male kitten, and 2 phenotypically normal female kittens from the same litter). All cats were examined via conventional echocardiography and 2-dimensional color TDI. No LVFW hypertrophy was detected in the 2 carriers or in the affected kitten when using conventional echocardiography and histologic examination, respectively. The LVFW also was normal for 1 affected male and at the upper limit of normal for the 2nd male. Conversely, LVFW dysfunction was detected in all affected and carrier cats with HFMD when using TDI. TDI consistently detects LVFW dysfunction in cats with HFMD despite the absence of myocardial hypertrophy. Therefore, TDI appears more sensitive than conventional echocardiography in detecting regional myocardial abnormalities.

Thymol, a dietary monoterpene phenol abrogates mitochondrial dysfunction in β-adrenergic agonist induced myocardial infarcted rats by inhibiting oxidative stress.

PubMed

Nagoor Meeran, M F; Jagadeesh, G S; Selvaraj, P

2016-01-25

Mitochondrial dysfunction has been suggested to be one of the important pathological events in isoproterenol (ISO), a synthetic catecholamine and β-adrenergic agonist induced myocardial infarction (MI). In this context, we have evaluated the impact of thymol against ISO induced oxidative stress and calcium uniporter malfunction involved in the pathology of mitochondrial dysfunction in rats. Male albino Wistar rats were pre and co-treated with thymol (7.5 mg/kg body weight) daily for 7 days. Isoproterenol (100 mg/kg body weight) was subcutaneously injected into rats on 6th and 7th day to induce MI. To explore the extent of cardiac mitochondrial damage, the activities/levels of cardiac marker enzymes, mitochondrial lipid peroxidation products, antioxidants, lipids, calcium, adenosine triphosphate and multi marker enzymes were evaluated. Isoproterenol induced myocardial infarcted rats showed a significant increase in the activities of cardiac diagnostic markers, heart mitochondrial lipid peroxidation, lipids, calcium, and a significant decrease in the activities/levels of heart mitochondrial superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, isocitrate, malate, α-ketoglutarate and NADH-dehydrogenases, cytochrome-C-oxidase, and adenosine triphosphate. Thymol pre and co-treatment showed near normalized effects on all the biochemical parameters studied. Transmission electron microscopic findings and mitochondrial swelling studies confirmed our biochemical findings. The in vitro study also revealed the potent free-radical scavenging activity of thymol. Thus, thymol attenuates the involvement of ISO against oxidative stress and calcium uniporter malfunction associated with mitochondrial dysfunction in rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chronic plus binge ethanol feeding induces myocardial oxidative stress, mitochondrial and cardiovascular dysfunction, and steatosis

PubMed Central

Matyas, Csaba; Varga, Zoltan V.; Mukhopadhyay, Partha; Paloczi, Janos; Lajtos, Tamas; Erdelyi, Katalin; Nemeth, Balazs T.; Nan, Mintong; Hasko, Gyorgy; Gao, Bin

2016-01-01

Alcoholic cardiomyopathy in humans develops in response to chronic excessive alcohol consumption; however, good models of alcohol-induced cardiomyopathy in mice are lacking. Herein we describe mouse models of alcoholic cardiomyopathies induced by chronic and binge ethanol (EtOH) feeding and characterize detailed hemodynamic alterations, mitochondrial function, and redox signaling in these models. Mice were fed a liquid diet containing 5% EtOH for 10, 20, and 40 days (d) combined with single or multiple EtOH binges (5 g/kg body wt). Isocalorically pair-fed mice served as controls. Left ventricular (LV) function and morphology were assessed by invasive pressure-volume conductance approach and by echocardiography. Mitochondrial complex (I, II, IV) activities, 3-nitrotyrosine (3-NT) levels, gene expression of markers of oxidative stress (gp91phox, p47phox), mitochondrial biogenesis (PGC1α, peroxisome proliferator-activated receptor α), and fibrosis were examined. Cardiac steatosis and fibrosis were investigated by histological/immunohistochemical methods. Chronic and binge EtOH feeding (already in 10 days EtOH plus single binge group) was characterized by contractile dysfunction (decreased slope of end-systolic pressure-volume relationship and preload recruitable stroke work), impaired relaxation (decreased time constant of LV pressure decay and maximal slope of systolic pressure decrement), and vascular dysfunction (impaired arterial elastance and lower total peripheral resistance). This was accompanied by enhanced myocardial oxidative/nitrative stress (3-NT; gp91phox; p47phox; angiotensin II receptor, type 1a) and deterioration of mitochondrial complex I, II, IV activities and mitochondrial biogenesis, excessive cardiac steatosis, and higher mortality. Collectively, chronic plus binge EtOH feeding in mice leads to alcohol-induced cardiomyopathies (National Institute on Alcohol Abuse and Alcoholism models) characterized by increased myocardial oxidative

Chronic plus binge ethanol feeding induces myocardial oxidative stress, mitochondrial and cardiovascular dysfunction, and steatosis.

PubMed

Matyas, Csaba; Varga, Zoltan V; Mukhopadhyay, Partha; Paloczi, Janos; Lajtos, Tamas; Erdelyi, Katalin; Nemeth, Balazs T; Nan, Mintong; Hasko, Gyorgy; Gao, Bin; Pacher, Pal

2016-06-01

Alcoholic cardiomyopathy in humans develops in response to chronic excessive alcohol consumption; however, good models of alcohol-induced cardiomyopathy in mice are lacking. Herein we describe mouse models of alcoholic cardiomyopathies induced by chronic and binge ethanol (EtOH) feeding and characterize detailed hemodynamic alterations, mitochondrial function, and redox signaling in these models. Mice were fed a liquid diet containing 5% EtOH for 10, 20, and 40 days (d) combined with single or multiple EtOH binges (5 g/kg body wt). Isocalorically pair-fed mice served as controls. Left ventricular (LV) function and morphology were assessed by invasive pressure-volume conductance approach and by echocardiography. Mitochondrial complex (I, II, IV) activities, 3-nitrotyrosine (3-NT) levels, gene expression of markers of oxidative stress (gp91phox, p47phox), mitochondrial biogenesis (PGC1α, peroxisome proliferator-activated receptor α), and fibrosis were examined. Cardiac steatosis and fibrosis were investigated by histological/immunohistochemical methods. Chronic and binge EtOH feeding (already in 10 days EtOH plus single binge group) was characterized by contractile dysfunction (decreased slope of end-systolic pressure-volume relationship and preload recruitable stroke work), impaired relaxation (decreased time constant of LV pressure decay and maximal slope of systolic pressure decrement), and vascular dysfunction (impaired arterial elastance and lower total peripheral resistance). This was accompanied by enhanced myocardial oxidative/nitrative stress (3-NT; gp91phox; p47phox; angiotensin II receptor, type 1a) and deterioration of mitochondrial complex I, II, IV activities and mitochondrial biogenesis, excessive cardiac steatosis, and higher mortality. Collectively, chronic plus binge EtOH feeding in mice leads to alcohol-induced cardiomyopathies (National Institute on Alcohol Abuse and Alcoholism models) characterized by increased myocardial oxidative

Deficiency in AMPK attenuates ethanol-induced cardiac contractile dysfunction through inhibition of autophagosome formation

PubMed Central

Guo, Rui; Ren, Jun

2012-01-01

Aims Binge drinking often triggers compromised myocardial contractile function while activating AMP-activated protein kinase (AMPK). Given the role of AMPK in the initiation of autophagy through the mammalian target of rapamycin complex 1 (mTORC1) and Unc51-like kinase (ULK1), this study was designed to examine the impact of AMPK deficiency on cardiac function and the mechanism involved with a focus on autophagy following an acute ethanol challenge. Methods and results Wild-type (WT) and transgenic mice overexpressing a kinase-dead (KD) α2 isoform (K45R mutation) of AMPK were challenged with ethanol. Glucose tolerance, echocardiography, Langendorff heart and cardiomyocyte contractile function, autophagy, and autophagic signalling including AMPK, acetyl-CoA carboxylase (ACC), mTOR, the mTORC1-associated protein Raptor, and ULK1 were examined. Ethanol exposure triggered glucose intolerance and compromised cardiac contraction accompanied by increased phosphorylation of AMPK and ACC as well as autophagosome accumulation (increased LC3II and p62), the effects of which were attenuated or mitigated by AMPK deficiency or inhibition. Ethanol dampened and stimulated, respectively, the phosphorylation of mTOR and Raptor, the effects of which were abolished by AMPK deficiency. ULK1 phosphorylation at Ser757 and Ser777 was down-regulated and up-regulated, respectively, by ethanol, the effect of which was nullified by AMPK deficiency or inhibition. Moreover, the ethanol challenge enhanced LC3 puncta in H9c2 cells and promoted cardiac contractile dysfunction, and these effects were ablated by the inhibition of autophagy or AMPK. Lysosomal inhibition failed to accentuate ethanol-induced increases in LC3II and p62. Conclusion In summary, these data suggest that ethanol exposure may trigger myocardial dysfunction through a mechanism associated with AMPK-mTORC1-ULK1-mediated autophagy. PMID:22451512

Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

PubMed Central

Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

2012-01-01

Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

Correlation between cardiac remodelling, function, and myocardial contractility in rat hearts 5 weeks after myocardial infarction.

PubMed

Gosselin, H; Qi, X; Rouleau, J L

1998-01-01

Early after infarction, ventricular dysfunction occurs as a result of loss of myocardial tissue. Although papillary muscle studies suggest that reduced myocardial contractility contributes to this ventricular dysfunction, in vivo studies indicate that at rest, cardiac output is normal or near normal, suggesting that contractility of the remaining viable myocardium of the ventricular wall is preserved. However, this has never been verified. To explore this further, 100 rats with various-sized myocardial infarctions had ventricular function assessed by Langendorff preparation or by isolated papillary muscle studies 5 weeks after infarction. Morphologic studies were also done. Rats with large infarctions (54%) had marked ventricular dilatation (dilatation index from 0.23 to 0.75, p < 0.01) and papillary muscle dysfunction (total tension from 6.7 to 3.2 g/mm2, p < 0.01) but only moderate left ventricular dysfunction (maximum developed tension from 206 to 151 mmHg (1 mmHg = 133.3 Pa), p < 0.01), a decrease less than one would expect with an infarct size of 54%. The contractility of the remaining viable myocardium of the ventricle was also moderately depressed (peak systolic midwall stress 91 to 60 mmHg, p < 0.01). Rats with moderate infarctions (32%) had less marked but still moderate ventricular dilatation (dilatation index 0.37, p < 0.001) and moderate papillary muscle dysfunction (total tension 4.2 g/mm2, p < 0.01). However, their decrease in ventricular function was only mild (maximum developed pressure 178 mmHg, p < 0.01) and less than one would expect with an infarct size of 32%. The remaining viable myocardium of the ventricular wall appeared to have normal contractility (peak systolic midwall stress = 86 mmHg, ns). We conclude that in this postinfarction model, in large myocardial infarctions, a loss of contractility of the remaining viable myocardium of the ventricular wall occurs as early as 5 weeks after infarction and that papillary muscle studies slightly

Velocity vector imaging fails to quantify regional myocardial dysfunction in a mouse model of isoprenaline-induced cardiotoxicity.

PubMed

Täng, Margareta Scharin; Redfors, Bjorn; Shao, Yangzhen; Omerovic, Elmir

2012-08-01

Regional myocardial deformation patterns are important in a variety of cardiac diseases, including stress-induced cardiomyopathy. Velocity-vector-based imaging is a speckle-tracking echocardiography (STE)-based algorithm that has been shown to allow in-depth cardiac phenotyping in humans. Regional posterior wall myocardial dysfunction occurs during severe isoprenaline stress in mice. We have previously shown that regional posterior wall end-systolic transmural strain decreases after severe isoprenaline toxicity in mice. We hypothesize that STE can detect and further quantify these perturbations. Twenty-three mice underwent echocardiographic examination using the VEVO2100 system. Regional transmural radial strain and strain rate were calculated in both parasternal short-axis and parasternal long-axis cine loops using the VisualSonics VEVO 2100 velocity vector imaging (VVI) STE algorithm. Eight C57BL/6 mice underwent baseline echocardiographic examination using the VisualSonics VEVO 770 system, which can acquire >1,000 frames/s cine loops. In a parasternal short-axis cine loop, the heart was divided into six segments, and regional fractional wall thickening (FWT) was assessed manually. The same protocols were also performed 90 minutes post 400 mg/kg intraperitoneally isoprenaline. Regional myocardial FWT is uniform at baseline but increases significantly in anterolateral segments, whereas it decreases significantly in posterior segments (P < 0.05). A similar pattern is seen using the VVI algorithm although the variance is larger, and differences are smaller and fail to reach significance. VVI is less sensitive in detecting regional perturbations in myocardial function than manual tracing, possibly due to the low frame rate in the cine loops used. © 2012, Wiley Periodicals, Inc.

Coronary arterial BK channel dysfunction exacerbates ischemia/reperfusion-induced myocardial injury in diabetic mice.

PubMed

Lu, Tong; Jiang, Bin; Wang, Xiao-Li; Lee, Hon-Chi

2016-09-01

The large conductance Ca(2+)-activated K(+) (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice. Combining patch-clamp techniques and cellular biological approaches, we found that diabetes facilitated the colocalization of angiotensin II (Ang II) type 1 receptors and BK channel α-subunits (BK-α), but not BK channel β1-subunits (BK-β1), in the caveolae of coronary SMCs. This caveolar compartmentation in vascular SMCs not only enhanced Ang II-mediated inhibition of BK-α but also produced a physical disassociation between BK-α and BK-β1, leading to increased infarct size in diabetic hearts. Most importantly, genetic ablation of caveolae integrity or pharmacological activation of coronary BK channels protected the cardiac function of diabetic mice from experimental I/R injury in both in vivo and ex vivo preparations. Our results demonstrate a vascular ionic mechanism underlying the poor outcome of myocardial injury in diabetes. Hence, activation of coronary BK channels may serve as a therapeutic target for cardiovascular complications of diabetes.

Asymptomatic cardiovascular manifestations in diabetes mellitus: left ventricular diastolic dysfunction and silent myocardial ischemia.

PubMed

Seferović-Mitrović, Jelena P; Lalić, Nebojsa M; Vujisić-Tesić, Bosiljka; Lalić, Katarina; Jotić, Aleksandra; Ristić, Arsen D; Giga, Vojislav; Tesić, Milorad; Milić, Natasa; Lukić, Ljiljana; Milicić, Tanja; Singh, Sandra; Seferović, Petar M

2011-01-01

Several cardiovascular manifestations in patients with diabetes may be asymptomatic. Left ventricular diastolic dysfunction (LVDD) is considered to be the earliest metabolic myocardial lesion in these patients, and can be diagnosed with tissue Doppler echocardiography. Silent myocardial ischemia (SMI) is a characteristic and frequently described form of ischemic heart disease in patients with diabetes. Objective The aim of the study was to assess the prevalence of LVDD and SMI in patients with type 2 diabetes, as well as to compare demographic, clinical, and metabolic data among defined groups (patients with LVDD, patients with SMI and patients with type 2 diabetes, without LVDD and SMI). We investigated 104 type 2 diabetic patients (mean age 55.4 +/- 9.1 years, 64.4% males) with normal blood pressure, prehypertension and arterial hypertension stage I. Study design included basic laboratory assessment and cardiological workup (transthoracic echocardiography and tissue Doppler, as well as the exercise stress echocardiography). LVDD was diagnosed in twelve patients (11.5%), while SMI was revealed in six patients (5.8%). Less patients with LVDD were using metformin, in comparison to other two groups (chi2 =12.152; p=0.002). Values of HDL cholesterol (F=4.515; p=0.013) and apolipoprotein A1 (F=5.128; p= 0.008) were significantly higher in patients with LVDD. The study confirmed asymptomatic cardiovascular complications in 17.3% patients with type 2 diabetes.

Right Ventricular Dysfunction Impairs Effort Tolerance Independent of Left Ventricular Function Among Patients Undergoing Exercise Stress Myocardial Perfusion Imaging.

PubMed

Kim, Jiwon; Di Franco, Antonino; Seoane, Tania; Srinivasan, Aparna; Kampaktsis, Polydoros N; Geevarghese, Alexi; Goldburg, Samantha R; Khan, Saadat A; Szulc, Massimiliano; Ratcliffe, Mark B; Levine, Robert A; Morgan, Ashley E; Maddula, Pooja; Rozenstrauch, Meenakshi; Shah, Tara; Devereux, Richard B; Weinsaft, Jonathan W

2016-11-01

Right ventricular (RV) and left ventricular (LV) function are closely linked due to a variety of factors, including common coronary blood supply. Altered LV perfusion holds the potential to affect the RV, but links between LV ischemia and RV performance, and independent impact of RV dysfunction on effort tolerance, are unknown. The population comprised 2051 patients who underwent exercise stress myocardial perfusion imaging and echo (5.5±7.9 days), among whom 6% had echo-evidenced RV dysfunction. Global summed stress scores were ≈3-fold higher among patients with RV dysfunction, attributable to increments in inducible and fixed LV perfusion defects (all P≤0.001). Regional inferior and lateral wall ischemia was greater among patients with RV dysfunction (both P<0.01), without difference in corresponding anterior defects (P=0.13). In multivariable analysis, inducible inferior and lateral wall perfusion defects increased the likelihood of RV dysfunction (both P<0.05) independent of LV function, fixed perfusion defects, and pulmonary artery pressure. Patients with RV dysfunction demonstrated lesser effort tolerance whether measured by exercise duration (6.7±2.8 versus 7.9±2.9 minutes; P<0.001) or peak treadmill stage (2.6±0.9 versus 3.1±1.0; P<0.001), paralleling results among patients with LV dysfunction (7.0±2.9 versus 8.0±2.9; P<0.001|2.7±1.0 versus 3.1±1.0; P<0.001 respectively). Exercise time decreased stepwise in relation to both RV and LV dysfunction (P<0.001) and was associated with each parameter independent of age or medication regimen. Among patients with known or suspected coronary artery disease, regional LV ischemia involving the inferior and lateral walls confers increased likelihood of RV dysfunction. RV dysfunction impairs exercise tolerance independent of LV dysfunction. © 2016 American Heart Association, Inc.

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

Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension: Relative Contribution of Fibrosis and Myofibril Stiffness.

PubMed

Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A C; de Man, Frances S

2016-07-01

The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. © 2016 The Authors.

Transient ventricular dysfunction after an asphyxiation event: stress or hypoxia?

PubMed

Valletta, Mary E; Haque, Ikram; Al-Mousily, Faris; Udassi, Jai; Saidi, Arwa

2008-11-01

This report of a pediatric patient with acute upper airway obstruction causing asphyxiation emphasizes the need to maintain clinical suspicion for acquired myocardial dysfunction, despite the presumed role of noncardiogenic causes for pulmonary edema after an acute upper airway obstruction. Case report. A tertiary pediatric intensive care unit. A 10-year-old girl with no significant medical history who developed flash pulmonary edema and acute myocardial dysfunction after an acute upper airway obstruction. Serial echocardiograms, exercise stress test, and coronary angiography were performed. Serial pro-brain natriuretic peptide, troponins, and CK-MB levels were also followed. Troponin level normalized approximately 7 days after the acute event. CK-MB and pro-brain natriuretic peptide levels decreased but had not completely normalized by time of discharge. The patient was discharged home 10 days after the event on an anticipated 6-month course of metoprolol without any signs or symptoms of cardiac dysfunction. Myocardial dysfunction is rarely documented in children after an acute upper airway obstruction or an asphyxiation event. Pediatric intensivists and hospitalists should maintain a high degree of clinical suspicion and screen for possible myocardial dysfunction in the pediatric patient with an acute severe hypoxic event especially when accompanied by pulmonary edema. Prompt evaluation ensures appropriate support. Additionally, some role may exist for early adrenergic receptor blockade.

PINK1 alleviates myocardial hypoxia-reoxygenation injury by ameliorating mitochondrial dysfunction

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

Li, Yang; Qiu, Liangxian; Liu, Xiping

PTEN inducible kinase-1 (PINK1) mutant induces mitochondrial dysfunction of cells, resulting in an inherited form of Parkinson's disease. However its exact role in the cardiomyocytes is unclear. The present study examined the function of PINK1 in hypoxia-reoxygenation (H/R) induced H9c2 cell damage and its potential mechanism. The H/R model in H9c2 cells was established by 6 h of hypoxia and 12 h of reoxygenation. The CCK8 and LDH assay indicated that the cell viability was obviously reduced after H/R. The expression of PINK1 was decreased in H/R-induced H9c2 cells compared with control group. The vector overexpressing PINK1 was constructed to transfect intomore » H/R-induced H9c2 cells. Our results showed that cell viability was increased, cell apoptosis and caspase 3, cytochrome C (Cyto C) levels were decreased after LV-PINK1 transfection. Furthermore, PINK1 overexpression stabilized electron transport chain (ETC) activity, increased ATP production, mPTP opening and mitochondrial membrane potential (MMP), inhibited ROS-generating mitochondria, implying PINK1 alleviates H/R induced mitochondrial dysfunction in cardiomyocytes. In addition, the TRAP-1 siRNA was transfected into PINK1 treated H9c2 cells after H/R to detected the molecular mechanism of PINK1 protecting cardiomyocytes. The results indicated that silence of TRAP-1 reversed the effects of PINK1 in H/R-induced H9c2 cells. In conclusion, these results suggest that PINK1 overexpression alleviates H/R-induced cell damage of H9c2 cells by phosphorylation of TRAP-1, and that is a valid approach for protection from myocardial I/R injury. - Highlights: • Effects of H/R on cell viability and PINK1 expression in H9c2 cells. • Effects of PINK1 on cell viability in H9c2 cells with H/R model. • Effects of PINK1 on mitochondrial dysfunction in H9c2 cells with H/R model. • PINK1 ameliorates H/R-induced H9c2 cells injury by activating p-TRAP-1.« less

Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

PubMed

Erdmann, Jeanette; Stark, Klaus; Esslinger, Ulrike B; Rumpf, Philipp Moritz; Koesling, Doris; de Wit, Cor; Kaiser, Frank J; Braunholz, Diana; Medack, Anja; Fischer, Marcus; Zimmermann, Martina E; Tennstedt, Stephanie; Graf, Elisabeth; Eck, Sebastian; Aherrahrou, Zouhair; Nahrstaedt, Janja; Willenborg, Christina; Bruse, Petra; Brænne, Ingrid; Nöthen, Markus M; Hofmann, Per; Braund, Peter S; Mergia, Evanthia; Reinhard, Wibke; Burgdorf, Christof; Schreiber, Stefan; Balmforth, Anthony J; Hall, Alistair S; Bertram, Lars; Steinhagen-Thiessen, Elisabeth; Li, Shu-Chen; März, Winfried; Reilly, Muredach; Kathiresan, Sekar; McPherson, Ruth; Walter, Ulrich; Ott, Jurg; Samani, Nilesh J; Strom, Tim M; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert

2013-12-19

Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce α1-sGC as well as β1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in α1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.

Oestradiol supplement minimises coronary occlusion-induced myocardial infarction and ventricular dysfunction in oophorectomised female rats.

PubMed

Zheng, Xiao-Pu; Ma, Ai-Qun; Dong, An-Ping; Wang, Shun; Jiang, Wen-Hui; Wang, Ting-Zhong; Fan, Fen-Ling; Ling, Shanhong

2011-09-15

Endogenous oestrogen deficiency after menopause is associated with high risk of acute cardiac events and the protection of exogenous oestrogen supplements remains uncertain. This study investigates whether oestrogen therapy protects the heart from ischemic injury in oophorectomised rats. Sexually mature female Sprague-Dawley rats (6 for each group) with bilateral oophorectomy underwent selective ligation (occlusion) of left coronary artery for 4 weeks. 17β-oestradiol (E2) supplements (10 μg, i.m., every other day) were started before (preventive-therapeutic supplement) or after coronary occlusion (therapeutic supplement). In oophorectomised rats plasma levels of E2 declined from 1301 ± 80 to 196 ± 48 pmol/L (p<0.01) and cardiac expression of oestrogen receptors (ER) decreased by ∼60%. E2 supplements recovered the ER expression. Selective ligation of left coronary led myocardial infarction in the left ventricle, with an increase in plasma cardiac troponin I (cTn-I), decrease in systolic blood pressure (SBP), and reduction of left ventricular pressures. Preventive-therapeutic but not therapeutic E2 supplement reduced cTn-I levels (from 21.9 ± 2.0 to 6.0 ± 0.3 ng/mL, p<0.01), minimised infarction (from 37.0 ± 1.2% to 18.1 ± 2.3%, p<0.05), increased SBP (from 82 ± 4.2 to 97 ± 4.4mm Hg, p<0.05), and improved left ventricular end pressures in the oophorectomised rats following coronary occlusion. Postmenopausal (ooporectomised) oestrogen supplement commenced before establishment of myocardial ischemia minimises myocardial infarction and ventricular dysfunction following the coronary artery occlusion. Cellular and molecular mechanisms underlying the cardiac protection of oestrogen therapy remain unclear, in which activation of cardiac ER expression and increasing in circulating CD90(+) stem cells may be involved. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Increase in mean platelet volume in patients with myocardial bridge.

PubMed

Bilen, Emine; Tanboga, Ibrahim Halil; Kurt, Mustafa; Kocak, Umran; Ayhan, Huseyin; Keles, Telat; Bozkurt, Engin

2013-01-01

Myocardial bridge is associated with atherosclerosis altered in shear stress and endothelial dysfunction. Mean platelet volume (MPV), a determinant of platelet activation, is shown to be related with atherosclerosis and endothelial dysfunction. In this study, we aimed to evaluate platelet function assessed by MPV in patients with myocardial bridge. Forty-two patients with myocardial bridge in the left anterior descending artery (LAD) and 43 age- and gender-matched healthy participants were included in the study. Myocardial bridging was defined as an intramyocardial systolic compression or milking of a segment of an epicardial coronary artery on angiography. For the entire study population, MPV was measured using an automatic blood counter. The study population consisted of 42 patients with myocardial bridge (52.7 ± 10.2, 76.2% male) and 43 age- and sex-matched healthy control participants (52.1 ± 10.4, 74.4% male). Compared to the control group, MPV value was significantly higher in patients with myocardial bridge (8.9 ± 1.24 vs 8.3 ± 0.78; P = .01). Further, there were no significant differences between groups regarding hemoglobin level, platelet count, fasting blood glucose, and creatinine levels. Our study findings indicated that myocardial bridge is associated with elevated MPV values. Our results might partly explain the increased cardiovascular events in patients with myocardial bridge.

Effect of uridine derivatives on myocardial stunning during postischemic reperfusion of rat heart.

PubMed

Sapronov, N S; Eliseev, V V; Rodionova, O M

2000-10-01

Uridine and uridine-5'-monophosphate prevent myocardial stunning during postischemic reperfusion of isolated rat heart. Uridine-5'-diphosphate does not prevent postischemic myocardial dysfunction, while uridine-5'-triphosphate aggravates it.

Local sympathetic denervation attenuates myocardial inflammation and improves cardiac function after myocardial infarction in mice

PubMed Central

Ziegler, Karin A; Ahles, Andrea; Wille, Timo; Kerler, Julia; Ramanujam, Deepak; Engelhardt, Stefan

2018-01-01

Abstract Aims Cardiac inflammation has been suggested to be regulated by the sympathetic nervous system (SNS). However, due to the lack of methodology to surgically eliminate the myocardial SNS in mice, neuronal control of cardiac inflammation remains ill-defined. Here, we report a procedure for local cardiac sympathetic denervation in mice and tested its effect in a mouse model of heart failure post-myocardial infarction. Methods and results Upon preparation of the carotid bifurcation, the right and the left superior cervical ganglia were localized and their pre- and postganglionic branches dissected before removal of the ganglion. Ganglionectomy led to an almost entire loss of myocardial sympathetic innervation in the left ventricular anterior wall. When applied at the time of myocardial infarction (MI), cardiac sympathetic denervation did not affect acute myocardial damage and infarct size. In contrast, cardiac sympathetic denervation significantly attenuated chronic consequences of MI, including myocardial inflammation, myocyte hypertrophy, and overall cardiac dysfunction. Conclusion These data suggest a critical role for local sympathetic control of cardiac inflammation. Our model of myocardial sympathetic denervation in mice should prove useful to further dissect the molecular mechanisms underlying cardiac neural control. PMID:29186414

Employing Extracellular Volume Cardiovascular Magnetic Resonance Measures of Myocardial Fibrosis to Foster Novel Therapeutics.

PubMed

Schelbert, Erik B; Sabbah, Hani N; Butler, Javed; Gheorghiade, Mihai

2017-06-01

Quantifying myocardial fibrosis (MF) with myocardial extracellular volume measures acquired during cardiovascular magnetic resonance promises to transform clinical care by advancing pathophysiologic understanding and fostering novel therapeutics. Extracellular volume quantifies MF by measuring the extracellular compartment depicted by the myocardial uptake of contrast relative to plasma. MF is a key domain of dysfunctional but viable myocardium among others (eg, microvascular dysfunction and cardiomyocyte/mitochondrial dysfunction). Although anatomically distinct, these domains may functionally interact. MF represents pathological remodeling in the heart associated with cardiac dysfunction and adverse outcomes likely mediated by interactions with the microvasculature and the cardiomyocyte. Reversal of MF improves key measures of cardiac dysfunction, so reversal of MF represents a likely mechanism for improved outcomes. Instead of characterizing the myocardium as homogenous tissue and using important yet still generic descriptors, such as thickness (hypertrophy) and function (diastolic or systolic), which lack mechanistic specificity, paradigms of cardiac disease have evolved to conceptualize myocardial disease and patient vulnerability based on the extent of disease involving its various compartments. Specifying myocardial compartmental involvement may then implicate cellular/molecular disease pathways for treatment and targeted pharmaceutical development and above all highlight the role of the cardiac-specific pathology in heart failure among myriad other changes in the heart and beyond. The cardiology community now requires phase 2 and 3 clinical trials to examine strategies for the regression/prevention of MF and eventually biomarkers to identify MF without reliance on cardiovascular magnetic resonance. It seems likely that efficacious antifibrotic therapy will improve outcomes, but definitive data are needed. © 2017 American Heart Association, Inc.

Cardioprotective Properties of Aerobic and Resistance Training Against Myocardial Infarction.

PubMed

Barboza, C A; Souza, G I H; Oliveira, J C M F; Silva, L M; Mostarda, C T; Dourado, P M M; Oyama, L M; Lira, F S; Irigoyen, M C; Rodrigues, B

2016-06-01

We evaluated the effects of aerobic and resistance exercise training on ventricular morphometry and function, physical capacity, autonomic function, as well as on ventricular inflammatory status in trained rats prior to myocardial infarction. Male Wistar rats were divided into the following groups: sedentary+Sham, sedentary+myocardial infarction, aerobic trained+myocardial infarction, and resistance trained+myocardial infarction. Sham and myocardial infarction were performed after training periods. In the days following the surgeries, evaluations were performed. Aerobic training prevents aerobic (to a greater extent) and resistance capacity impairments, ventricular dysfunction, baroreflex sensitivity and autonomic disorders (vagal tonus decrease and sympathetic tonus increase) triggered by myocardial infarction. Resistance training was able to prevent negative changes to aerobic and resistance capacity (to a greater extent) but not to ventricular dysfunction, and it prevented cardiovascular sympathetic increments. Additionally, both types of training reduced left ventricle inflammatory cytokine concentration. Our results suggest that aerobic and, for the first time, dynamic resistance training were able to reduce sympathetic tonus to the heart and vessels, as well as preventing the increase in pro-inflammatory cytokine concentrations in the left ventricle of trained groups. These data emphasizes the positive effects of aerobic and dynamic resistance training on the prevention of the negative changes triggered by myocardial infarction. © Georg Thieme Verlag KG Stuttgart · New York.

Complex inhibition of autophagy by mitochondrial aldehyde dehydrogenase shortens lifespan and exacerbates cardiac aging.

PubMed

Zhang, Yingmei; Wang, Cong; Zhou, Jingmin; Sun, Aijun; Hueckstaedt, Lindsay K; Ge, Junbo; Ren, Jun

2017-08-01

Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a cascade of biological processes including aging. A number of autophagy regulators have been identified. Here we demonstrated that mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme with the most common single point mutation in humans, governs cardiac aging through regulation of autophagy. Myocardial mechanical and autophagy properties were examined in young (4months) and old (26-28months) wild-type (WT) and global ALDH2 transgenic mice. ALDH2 overexpression shortened lifespan by 7.7% without affecting aging-associated changes in plasma metabolic profiles. Myocardial function was compromised with aging associated with cardiac hypertrophy, the effects were accentuated by ALDH2. Aging overtly suppressed autophagy and compromised autophagy flux, the effects were exacerbated by ALDH2. Aging dampened phosphorylation of JNK, Bcl-2, IKKβ, AMPK and TSC2 while promoting phosphorylation of mTOR, the effects of which were exaggerated by ALDH2. Co-immunoprecipitation revealed increased dissociation between Bcl-2 and Beclin-1 (result of decreased Bcl-2 phosphorylation) in aging, the effect of which was exacerbated with ALDH2. Chronic treatment of the autophagy inducer rapamycin alleviated aging-induced cardiac dysfunction in both WT and ALDH2 mice. Moreover, activation of JNK and inhibition of either Bcl-2 or IKKβ overtly attenuated ALDH2 activation-induced accentuation of cardiomyocyte aging. Examination of the otherwise elderly individuals revealed a positive correlation between cardiac function/geometry and ALDH2 gene mutation. Taken together, our data revealed that ALDH2 enzyme may suppress myocardial autophagy possibly through a complex JNK-Bcl-2 and IKKβ-AMPK-dependent mechanism en route to accentuation of myocardial remodeling and contractile dysfunction in aging. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure

Carriers of the hypertrophic cardiomyopathy MYBPC3 mutation are characterized by reduced myocardial efficiency in the absence of hypertrophy and microvascular dysfunction.

PubMed

Timmer, Stefan A J; Germans, Tjeerd; Brouwer, Wessel P; Lubberink, Mark; van der Velden, Jolanda; Wilde, Arthur A M; Christiaans, Imke; Lammertsma, Adriaan A; Knaapen, Paul; van Rossum, Albert C

2011-12-01

Next to left ventricular (LV) hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by microvascular dysfunction and reduced myocardial external efficiency (MEE). Insights into the presence of these abnormalities as early markers of disease are of clinical importance in risk stratification, and development of therapeutic approaches. Therefore, the aim was to investigate myocardial perfusion and energetics in genotype-positive, phenotype-negative HCM subjects (carriers). Fifteen carriers of an MYBPC3 mutation underwent [(15)O]water positron emission tomography (PET) to assess myocardial blood flow (MBF). [(11)C]acetate PET was performed to obtain myocardial oxygen consumption (MVO(2)). By use of cardiovascular magnetic resonance imaging, LV volumes and mass were defined to calculate MEE, i.e. the ratio between external work and MVO(2). Eleven healthy, genotype-negative, family relatives underwent similar scanning protocols to serve as a control group. Left ventricular mass was comparable between carriers and controls (93 ± 25 vs. 99 ± 21 g, P= 0.85), as was MBF at rest (1.19 ± 0.34 vs. 1.18 ± 0.32 mL min(-1) g(-1), P= 0.92), and during hyperaemia (3.87 ± 0.75 vs. 3.96 ± 0.86 mL min(-1) g(-1), P= 0.77). Myocardial oxygen consumption averaged 0.137 ± 0.057 mL min(-1) g(-1) in carriers and was not significantly different from controls (0.125 ± 0.043 mL min(-1) g(-1), P= 0.29). Cardiac work, however, was slightly reduced in carriers (7398 ± 1384 vs. 9139 ± 2484 mmHg mL in controls, P= 0.08). As a consequence, MEE was significantly decreased in carriers (27 ± 10 vs. 36 ± 8% in controls, P= 0.02). Carriers display reduced myocardial work generation in relation to oxygen consumption, in the absence of hypertrophy and flow abnormalities. Hence, impaired myocardial energetics may constitute a primary component of HCM pathogenesis.

Coronary microvascular dysfunction equivalent to left main coronary artery disease.

PubMed

Panç, Cafer; Kocaağa, Mehmet; Erdoğan, Onur; Sarıkaya, Remzi; Umman, Sabahattin

2017-04-01

Coronary microvascular dysfunction, also known as cardiac syndrome X, is a clinical syndrome presenting with typical angina and evidence of myocardial ischemia in the absence of flow-limiting stenosis on coronary angiography. Of patients undergoing coronary angiography due to suspected myocardial ischemia, 50% are found to have normal or near-normal coronary arteries. Described in this case report is a patient who developed hypotension and ST segment depressions during treadmill exercise test. Left main coronary artery or multivessel disease was suspected. Coronary angiography was normal, but coronary flow reserve measurement revealed severe microvascular dysfunction.

Myocardial Ischemia Induces SDF-1α Release in Cardiac Surgery Patients.

PubMed

Kim, Bong-Sung; Jacobs, Denise; Emontzpohl, Christoph; Goetzenich, Andreas; Soppert, Josefin; Jarchow, Mareike; Schindler, Lisa; Averdunk, Luisa; Kraemer, Sandra; Marx, Gernot; Bernhagen, Jürgen; Pallua, Norbert; Schlemmer, Heinz-Peter; Simons, David; Stoppe, Christian

2016-06-01

In the present observational study, we measured serum levels of the chemokine stromal cell-derived factor-1α (SDF-1α) in 100 patients undergoing cardiac surgery with cardiopulmonary bypass at seven distinct time points including preoperative values, myocardial ischemia, reperfusion, and the postoperative course. Myocardial ischemia triggered a marked increase of SDF-1α serum levels whereas cardiac reperfusion had no significant influence. Perioperative SDF-1α serum levels were influenced by patients' characteristics (e.g., age, gender, aspirin intake). In an explorative analysis, we observed an inverse association between SDF-1α serum levels and the incidence of organ dysfunction. In conclusion, time of myocardial ischemia was identified as the key stimulus for a significant upregulation of SDF-1α, indicating its role as a marker of myocardial injury. The inverse association between SDF-1α levels and organ dysfunction association encourages further studies to evaluate its organoprotective properties in cardiac surgery patients.

Chagas' heart disease: gender differences in myocardial damage assessed by cardiovascular magnetic resonance.

PubMed

Assunção, Antonildes N; Jerosch-Herold, Michael; Melo, Rodrigo L; Mauricio, Alejandra V; Rocha, Liliane; Torreão, Jorge A; Fernandes, Fabio; Ianni, Barbara M; Mady, Charles; Ramires, José A F; Kalil-Filho, Roberto; Rochitte, Carlos E

2016-11-28

Since a male-related higher cardiovascular morbidity and mortality in patients with Chagas' heart disease has been reported, we aimed to investigate gender differences in myocardial damage assessed by cardiovascular magnetic resonance (CMR). Retrospectively, 62 seropositive Chagas' heart disease patients referred to CMR (1.5 T) and with low probability of having significant coronary artery disease were included in this analysis. Amongst both sexes, there was a strong negative correlation between LV ejection fraction and myocardial fibrosis (male r = 0.64, female r = 0.73, both P < 0.001), with males showing significantly greater myocardial fibrosis (P = 0.002) and lower LV ejection fraction (P < 0.001) than females. After adjustment for potential confounders, gender remained associated with myocardial dysfunction, and 53% of the effect was mediated by myocardial fibrosis (P for mediation = 0.004). Also, the transmural pattern was more prevalent among male patients (23.7 vs. 9.9%, P < 0.001) as well as the myocardial heterogeneity or gray zone (2.2 vs. 1.3 g, P = 0.003). We observed gender-related differences in myocardial damage assessed by CMR in patients with Chagas' heart disease. As myocardial fibrosis and myocardial dysfunction are associated to cardiovascular outcomes, our findings might help to understand the poorer prognosis observed in males in Chagas' disease.

Both Selenium Deficiency and Modest Selenium Supplementation Lead to Myocardial Fibrosis in Mice via Effects on Redox-Methylation Balance

PubMed Central

Metes-Kosik, Nicole; Luptak, Ivan; DiBello, Patricia M.; Handy, Diane E.; Tang, Shiow-Shih; Zhi, Hui; Qin, Fuzhong; Jacobsen, Donald W.; Loscalzo, Joseph; Joseph, Jacob

2013-01-01

Scope Selenium has complex effects in vivo on multiple homeostatic mechanisms such as redox balance, methylation balance, and epigenesis, via its interaction with the methionine-homocysteine cycle. In this study, we examined the hypothesis that selenium status would modulate both redox and methylation balance and thereby modulate myocardial structure and function. Methods and Results We examined the effects of selenium deficient (<0.025 mg/kg), control (0.15 mg/kg), and selenium supplemented (0.5 mg/kg) diets on myocardial histology, biochemistry and function in adult C57/BL6 mice. Selenium deficiency led to reactive myocardial fibrosis and systolic dysfunction accompanied by increased myocardial oxidant stress. Selenium supplementation significantly reduced methylation potential, DNA methyltransferase activity and DNA methylation. In mice fed the supplemented diet, inspite of lower oxidant stress, myocardial matrix gene expression was significantly altered resulting in reactive myocardial fibrosis and diastolic dysfunction in the absence of myocardial hypertrophy. Conclusions Our results indicate that both selenium deficiency and modest selenium supplementation leads to a similar phenotype of abnormal myocardial matrix remodeling and dysfunction in the normal heart. The crucial role selenium plays in maintaining the balance between redox and methylation pathways needs to be taken into account while optimizing selenium status for prevention and treatment of heart failure. PMID:23097236

Cardiac-specific inactivation of LPP3 in mice leads to myocardial dysfunction and heart failure.

PubMed

Chandra, Mini; Escalante-Alcalde, Diana; Bhuiyan, Md Shenuarin; Orr, Anthony Wayne; Kevil, Christopher; Morris, Andrew J; Nam, Hyung; Dominic, Paari; McCarthy, Kevin J; Miriyala, Sumitra; Panchatcharam, Manikandan

2018-04-01

Lipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates. We observed that lack of Lpp3 enhanced cardiomyocyte hypertrophy based on analysis of cell surface area. We found that lack of Lpp3 signaling was mediated through the activation of Rho and phospho-ERK pathways. There are increased levels of fetal genes Natriuretic Peptide A and B (Nppa and Nppb) expression indicating myocardial dysfunction. These mice also demonstrate mitochondrial dysfunction as evidenced by a significant decrease (P < 0.001) in the basal oxygen consumption rate, mitochondrial ATP production, and spare respiratory capacity as measured through mitochondrial bioenergetics. Histology and transmission electron microscopy of these hearts showed disrupted sarcomere organization and intercalated disc, with a prominent disruption of the cristae and vacuole formation in the mitochondria. Our findings suggest that LPA/LPP3-signaling nexus plays an important role in normal function of cardiomyocytes. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Curcumin ameliorates cardiac dysfunction induced by mechanical trauma.

PubMed

Li, Xintao; Cao, Tingting; Ma, Shuo; Jing, Zehao; Bi, Yue; Zhou, Jicheng; Chen, Chong; Yu, Deqin; Zhu, Liang; Li, Shuzhuang

2017-11-05

Curcumin, a phytochemical component derived from turmeric (Carcuma longa), has been extensively investigated because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play critical roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This research was designed to identify the protective effect of curcumin on posttraumatic cardiac dysfunction and investigate its underlying mechanism. Noble-Collip drum was used to prepare a mechanical trauma (MT) model of rats, and the hemodynamic responses of traumatized rats were observed by ventricular intubation 12h after trauma. Myocardial apoptosis was determined through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay. Tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) generated by monocytes and myocardial cells were identified through enzyme-linked immunosorbent assay (ELISA), and the intracellular alteration of Ca 2+ in cardiomyocytes was examined through confocal microscopy. In vivo, curcumin effectively ameliorated MT-induced secondary cardiac dysfunction and significantly decreased the apoptotic indices of the traumatized myocardial cells. In vitro, curcumin inhibited TNF-α production by monocytes and reduced the circulating TNF-α levels. With curcumin pretreatment, ROS production and Ca 2+ overload in H9c2 cells were attenuated when these cells were incubated with traumatic plasma. Therefore, curcumin can effectively ameliorate MT-induced cardiac dysfunction mainly by inhibiting systemic inflammatory responses and by weakening oxidative stress reaction and Ca 2+ overload in cardiomyocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

Relationship of biomarkers of extracellular matrix with myocardial function in Type 2 diabetes mellitus.

PubMed

Liu, Ju-Hua; Chen, Yan; Zhen, Zhe; Ho, Lai-Ming; Tsang, Anita; Yuen, Michele; Lam, Karen; Tse, Hung-Fat; Yiu, Kai-Hang

2017-07-01

The study evaluated the relationship of extracellular matrix and renin angiotensin system with myocardial dysfunction in Type 2 diabetes mellitus. All patients underwent resting and exercise echocardiography, including conventional parameters, E/E' ratio, global longitudinal strain and diastolic function reserve index. Plasma matrix metalloproteinase-1, TIMP-1, amino-terminal propeptide of type I and type III procollagen and renin angiotensin system activity were measured. As patients with diastolic dysfunction had a higher plasma level of TIMP-1 and propeptide of type III procollagen than those with no diastolic dysfunction. After multivariate adjustment, TIMP-1 associated with E/E' (both at rest and stress) and diastolic function reserve index. TIMP-1 is independently associated with myocardial diastolic dysfunction in patients with Type 2 diabetes mellitus.

Myocardial Hypertrophy and Its Role in Heart Failure with Preserved Ejection Fraction

PubMed Central

Heinzel, Frank R.; Hohendanner, Felix; Jin, Ge; Sedej, Simon; Edelmann, Frank

2015-01-01

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load and cytokines associated with arterial hypertension, chronic kidney disease, diabetes and other co-morbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood but may include extracellular matrix changes, vascular dysfunction as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca2+ turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound co-morbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training on the other hand, in clinical trials improved exercise tolerance and diastolic function but did not reduce LVH. Thus, current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF. PMID:26183480

Adenosine A2A receptor agonist prevents cardiac remodeling and dysfunction in spontaneously hypertensive male rats after myocardial infarction

PubMed Central

da Silva, Jaqueline S; Gabriel-Costa, Daniele; Sudo, Roberto T; Wang, Hao; Groban, Leanne; Ferraz, Emanuele B; Nascimento, José Hamilton M; Fraga, Carlos Alberto M; Barreiro, Eliezer J; Zapata-Sudo, Gisele

2017-01-01

Background This work evaluated the hypothesis that 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294), an agonist of adenosine A2A receptor, could be beneficial for preventing cardiac dysfunction due to hypertension associated with myocardial infarction (MI). Methods Male spontaneously hypertensive rats (SHR) were randomly divided into four groups (six animals per group): sham-operation (SHR-Sham), and myocardial infarction rats (SHR-MI) were treated orally either with vehicle or LASSBio-294 (10 and 20 mg.kg−1.d−1) for 4 weeks. Echocardiography and in vivo hemodynamic parameters measured left ventricle (LV) structure and function. Exercise tolerance was evaluated using a treadmill test. Cardiac remodeling was accessed by LV collagen deposition and tumor necrosis factor α expression. Results Early mitral inflow velocity was significantly reduced in the SHR-MI group, and there was significant recovery in a dose-dependent manner after treatment with LASSBio-294. Exercise intolerance observed in the SHR-MI group was prevented by 10 mg.kg−1.d−1 of LASS-Bio-294, and exercise tolerance exceeded that of the SHR-Sham group at 20 mg.kg−1.d−1. LV end-diastolic pressure increased after MI, and this was prevented by 10 and 20 mg.kg−1.d−1 of LASSBio-294. Sarcoplasmic reticulum Ca2+ ATPase levels were restored in a dose-dependent manner after treatment with LASSBio-294. Fibrosis and inflammatory processes were also counteracted by LASSBio-294, with reductions in LV collagen deposition and tumor necrosis factor α expression. Conclusion In summary, oral administration of LASSBio-294 after MI in a dose-dependent manner prevented the development of cardiac dysfunction, demonstrating this compound’s potential as an alternative treatment for heart failure in the setting of ischemic heart disease with superimposed chronic hypertension. PMID:28293100

Endothelial function is associated with myocardial diastolic function in women with systemic lupus erythematosus.

PubMed

Chin, Calvin W L; Chin, Chee-Yang; Ng, Marie X R; Le, Thu-Thao; Huang, Fei-Qiong; Fong, Kok-Yong; Thumboo, Julian; Tan, Ru-San

2014-09-01

Endothelial dysfunction is associated with traditional and systemic lupus erythematosus (SLE)-specific risk factors, and early data suggest reversibility of endothelial dysfunction with therapy. The clinical relevance of endothelial function assessment has been limited by the lack of studies, demonstrating its prognostic significance and impact on early myocardial function. Therefore, we aimed to determine the association between endothelial and myocardial diastolic function in SLE women. Women with SLE and no coronary artery disease were prospectively recruited and underwent radionuclide myocardial perfusion imaging (MPI) (Jetstream, Philips, the Netherlands) to exclude subclinical myocardial ischemia. Cardiac and vascular functions were assessed in all patients (Alpha 10, Aloka, Tokyo). Diastolic function was assessed using pulse wave early (E) and late mitral blood inflow and myocardial tissue Doppler (mean of medial and lateral annulus e') velocities. Endothelial function was measured using brachial artery flow-mediated vasodilatation (FMD%). Univariate and multivariate linear regressions were used to assess the association between FMD% and myocardial diastolic function, adjusting for potential confounders. Thirty-eight patients without detectable myocardial ischemia on MPI were studied (mean age 44 ± 10 years; mean disease duration 14 ± 6 years). About 61 % of patients had normal diastolic function (E/e' ≤ 8), and 5 % of patients had definite diastolic dysfunction with E/e' > 13 (mean 7.1 ± 2.9). FMD% was associated with E/e' (regression coefficient β = -0.35; 95 % CI -0.62 to -0.08; p = 0.01) independent of systolic blood pressure, age, and SLICC/ACR Damage Index.

Left ventricular function abnormalities as a manifestation of silent myocardial ischemia.

PubMed

Lambert, C R; Conti, C R; Pepine, C J

1986-11-01

A large body of evidence exists indicating that left ventricular dysfunction is a common occurrence in patients with severe coronary artery disease and represents silent or asymptomatic myocardial ischemia. Such dysfunction probably occurs early in the time course of every ischemic episode in patients with coronary artery disease whether symptoms are eventually manifested or not. The pathophysiology of silent versus symptomatic left ventricular dysfunction due to ischemia appears to be identical. Silent ischemia-related left ventricular dysfunction can be documented during spontaneous or stress-induced perturbations in the myocardial oxygen supply/demand ratio. It also may be detected by nitroglycerin-induced improvement in ventricular function or by salutary changes in wall motion following revascularization. Silent left ventricular dysfunction is a very early occurrence during ischemia and precedes electrocardiographic abnormalities. In this light, its existence should always be kept in mind when dealing with patients with ischemic heart disease. It can be hypothesized that because silent ischemia appears to be identical to ischemia with symptoms in a pathophysiologic sense, prognosis and treatment in both cases should be the same.

Targeting inflammatory pathways in myocardial infarction

PubMed Central

Christia, Panagiota; Frangogiannis, Nikolaos G

2013-01-01

Acute cardiomyocyte necrosis in the infarcted heart generates Damage-Associated Molecular Patterns (DAMPs), activating complement and Toll-Like Receptor (TLR)/Interleukin (IL)-1 signaling, and triggering an intense inflammatory reaction. Infiltrating leukocytes clear the infarct from dead cells, while activating reparative pathways that lead to formation of a scar. As the infarct heals the ventricle remodels; the geometric, functional and molecular alterations associated with post-infarction remodeling are driven by the inflammatory cascade and are involved in the development of heart failure. Because unrestrained inflammation in the infarcted heart induces matrix degradation and cardiomyocyte apoptosis, timely suppression of the post-infarction inflammatory reaction may be crucial to protect the myocardium from dilative remodeling and progressive dysfunction. Inhibition and resolution of post-infarction inflammation involves mobilization of inhibitory mononuclear cell subsets and requires activation of endogenous STOP signals. Our manuscript discusses the basic cellular and molecular events involved in initiation, activation and resolution of the post-infarction inflammatory response, focusing on identification of therapeutic targets. The failure of anti-integrin approaches in patients with myocardial infarction and a growing body of experimental evidence suggest that inflammation may not increase ischemic cardiomyocyte death, but accentuates matrix degradation causing dilative remodeling. Given the pathophysiologic complexity of post-infarction remodeling, personalized biomarker-based approaches are needed to target patient subpopulations with dysregulated inflammatory and reparative responses. Inhibition of pro-inflammatory signals (such as IL-1 and Monocyte Chemoattractant Protein-1) may be effective in patients with defective resolution of post-infarction inflammation who exhibit progressive dilative remodeling. In contrast, patients with predominant

Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance.

PubMed

Metes-Kosik, Nicole; Luptak, Ivan; Dibello, Patricia M; Handy, Diane E; Tang, Shiow-Shih; Zhi, Hui; Qin, Fuzhong; Jacobsen, Donald W; Loscalzo, Joseph; Joseph, Jacob

2012-12-01

Selenium has complex effects in vivo on multiple homeostatic mechanisms such as redox balance, methylation balance, and epigenesis, via its interaction with the methionine-homocysteine cycle. In this study, we examined the hypothesis that selenium status would modulate both redox and methylation balance and thereby modulate myocardial structure and function. We examined the effects of selenium-deficient (<0.025 mg/kg), control (0.15 mg/kg), and selenium-supplemented (0.5 mg/kg) diets on myocardial histology, biochemistry and function in adult C57/BL6 mice. Selenium deficiency led to reactive myocardial fibrosis and systolic dysfunction accompanied by increased myocardial oxidant stress. Selenium supplementation significantly reduced methylation potential, DNA methyltransferase activity and DNA methylation. In mice fed the supplemented diet, inspite of lower oxidant stress, myocardial matrix gene expression was significantly altered resulting in reactive myocardial fibrosis and diastolic dysfunction in the absence of myocardial hypertrophy. Our results indicate that both selenium deficiency and modest selenium supplementation leads to a similar phenotype of abnormal myocardial matrix remodeling and dysfunction in the normal heart. The crucial role selenium plays in maintaining the balance between redox and methylation pathways needs to be taken into account while optimizing selenium status for prevention and treatment of heart failure. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reducing myocardial infarct size: challenges and future opportunities

PubMed Central

Bulluck, Heerajnarain; Yellon, Derek M; Hausenloy, Derek J

2016-01-01

Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is ‘myocardial reperfusion injury’, a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-of-concept clinical studies—however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury. PMID:26674987

Cardiac-restricted Overexpression of TRAF3 Interacting Protein 2 (TRAF3IP2) Results in Spontaneous Development of Myocardial Hypertrophy, Fibrosis, and Dysfunction *

PubMed Central

Sakamuri, Siva S. V. P.; Siddesha, Jalahalli M.; Saifudeen, Zubaida; Ma, Lixin; Siebenlist, Ulrich; Gardner, Jason D.; Chandrasekar, Bysani

2016-01-01

TRAF3IP2 (TRAF3 interacting protein 2; previously known as CIKS or Act1) is a key intermediate in the normal inflammatory response and the pathogenesis of various autoimmune and inflammatory diseases. Induction of TRAF3IP2 activates IκB kinase (IKK)/NF-κB, JNK/AP-1, and c/EBPβ and stimulates the expression of various inflammatory mediators with negative myocardial inotropic effects. To investigate the role of TRAF3IP2 in heart disease, we generated a transgenic mouse model with cardiomyocyte-specific TRAF3IP2 overexpression (TRAF3IP2-Tg). Echocardiography, magnetic resonance imaging, and pressure-volume conductance catheterization revealed impaired cardiac function in 2-month-old male transgenic (Tg) mice as evidenced by decreased ejection fraction, stroke volume, cardiac output, and peak ejection rate. Moreover, the male Tg mice spontaneously developed myocardial hypertrophy (increased heart/body weight ratio, cardiomyocyte cross-sectional area, GATA4 induction, and fetal gene re-expression). Furthermore, TRAF3IP2 overexpression resulted in the activation of IKK/NF-κB, JNK/AP-1, c/EBPβ, and p38 MAPK and induction of proinflammatory cytokines, chemokines, and extracellular matrix proteins in the heart. Although myocardial hypertrophy decreased with age, cardiac fibrosis (increased number of myofibroblasts and enhanced expression and deposition of fibrillar collagens) increased progressively. Despite these adverse changes, TRAF3IP2 overexpression did not result in cell death at any time period. Interestingly, despite increased mRNA expression, TRAF3IP2 protein levels and activation of its downstream signaling intermediates remained unchanged in the hearts of female Tg mice. The female Tg mice also failed to develop myocardial hypertrophy. In summary, these results demonstrate that overexpression of TRAF3IP2 in male mice is sufficient to induce myocardial hypertrophy, cardiac fibrosis, and contractile dysfunction. PMID:27466370

Optimal Timing of Surgical Revascularization for Myocardial Infarction and Left Ventricular Dysfunction

PubMed Central

Wang, Rong; Cheng, Nan; Xiao, Cang-Song; Wu, Yang; Sai, Xiao-Yong; Gong, Zhi-Yun; Wang, Yao; Gao, Chang-Qing

2017-01-01

Background: The optimal timing of surgical revascularization for patients presenting with ST-segment elevation myocardial infarction (STEMI) and impaired left ventricular function is not well established. This study aimed to examine the timing of surgical revascularization after STEMI in patients with ischemic heart disease and left ventricular dysfunction (LVD) by comparing early and late results. Methods: From January 2003 to December 2013, there were 2276 patients undergoing isolated coronary artery bypass grafting (CABG) in our institution. Two hundred and sixty-four (223 male, 41 females) patients with a history of STEMI and LVD were divided into early revascularization (ER, <3 weeks), mid-term revascularization (MR, 3 weeks to 3 months), and late revascularization (LR, >3 months) groups according to the time interval from STEMI to CABG. Mortality and complication rates were compared among the groups by Fisher's exact test. Cox regression analyses were performed to examine the effect of the time interval of surgery on long-term survival. Results: No significant differences in 30-day mortality, long-term survival, freedom from all-cause death, and rehospitalization for heart failure existed among the groups (P > 0.05). More patients in the ER group (12.90%) had low cardiac output syndrome than those in the MR (2.89%) and LR (3.05%) groups (P = 0.035). The mean follow-up times were 46.72 ± 30.65, 48.70 ± 32.74, and 43.75 ± 32.43 months, respectively (P = 0.716). Cox regression analyses showed a severe preoperative condition (odds ratio = 7.13, 95% confidence interval 2.05–24.74, P = 0.002) rather than the time interval of CABG (P > 0.05) after myocardial infarction was a risk factor of long-term survival. Conclusions: Surgical revascularization for patients with STEMI and LVD can be performed at different times after STEMI with comparable operative mortality and long-term survival. However, ER (<3 weeks) has a higher incidence of postoperative low cardiac

Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function

PubMed Central

Saxena, Amit; Dobaczewski, Marcin; Rai, Vikrant; Haque, Zaffar; Chen, Wei; Li, Na

2014-01-01

Regulatory T cells (Tregs) play a pivotal role in suppressing immune responses regulating behavior and gene expression in effector T cells, macrophages, and dendritic cells. Tregs infiltrate the infarcted myocardium; however, their role the inflammatory and reparative response after myocardial infarction remains poorly understood. We used FoxP3EGFP reporter mice to study Treg trafficking in the infarcted heart and examined the effects of Treg depletion on postinfarction remodeling using an anti-CD25 antibody. Moreover, we investigated the in vitro effects of Tregs on cardiac fibroblast phenotype and function. Low numbers of Tregs infiltrated the infarcted myocardium after 24–72 h of reperfusion. Treg depletion had no significant effects on cardiac dysfunction and scar size after reperfused myocardial infarction but accelerated ventricular dilation and accentuated apical remodeling. Enhanced myocardial dilation in Treg-depleted animals was associated with increased expression of chemokine (C-C motif) ligand 2 and accentuated macrophage infiltration. In vitro, Tregs modulated the cardiac fibroblast phenotype, reducing expression of α-smooth muscle actin, decreasing expression of matrix metalloproteinase-3, and attenuating contraction of fibroblast-populated collagen pads. Our findings suggest that endogenous Tregs have modest effects on the inflammatory and reparative response after myocardial infarction. However, the anti-inflammatory and matrix-preserving properties of Tregs may suggest a role for Treg-based cell therapy in the attenuation of adverse postinfarction remodeling. PMID:25128167

Regulation of Heat Shock Proteins 27 and 70, p-Akt/p-eNOS and MAPKs by Naringin Dampens Myocardial Injury and Dysfunction In Vivo after Ischemia/Reperfusion

PubMed Central

Rani, Neha; Bharti, Saurabh; Manchanda, Mansi; Nag, T. C.; Ray, Ruma; Chauhan, S. S.; Kumari, Santosh; Arya, Dharamvir Singh

2013-01-01

Naringin has antioxidant properties that could improve redox-sensitive myocardial ischemia reperfusion (IR) injury. This study was designed to investigate whether naringin restores the myocardial damage and dysfunction in vivo after IR and the mechanisms underlying its cardioprotective effects. Naringin (20–80 mg/kg/day, p.o.) or saline were administered to rats for 14 days and the myocardial IR injury was induced on 15th day by occluding the left anterior descending coronary artery for 45 min and subsequent reperfusion for 60 min. Post-IR rats exhibited pronounced cardiac dysfunction as evidenced by significantly decreased mean arterial pressure, heart rate, +LVdP/dt max (inotropic state), -LVdP/dt max (lusitropic state) and increased left ventricular end diastolic pressure as compared to sham group, which was improved by naringin. Further, on histopathological and ultrastructural assessments myocardium and myocytes appeared more normal in structure and the infarct size was reduced significantly in naringin 40 and 80 mg/kg/day group. This amelioration of post-IR-associated cardiac injury by naringin was accompanied by increased nitric oxide (NO) bioavailability, decreased NO inactivation to nitrotyrosine, amplified protein expressions of Hsp27, Hsp70, β-catenin and increased p-eNOS/eNOS, p-Akt/Akt, and p-ERK/ERK ratio. In addition, IR-induced TNF-α/IKK-β/NF-κB upregulation and JNK phosphorylation were significantly attenuated by naringin. Moreover, western blotting and immunohistochemistry analysis of apoptotic signaling pathway further established naringin cardioprotective potential as it upregulated Bcl-2 expression and downregulated Bax and Caspase-3 expression with reduced TUNEL positivity. Naringin also normalized the cardiac injury markers (lactate dehydrogenase and creatine kinase-MB), endogenous antioxidant activities (superoxide dismutase, reduced glutathione and glutathione peroxidase) and lipid peroxidation levels. Thus, naringin restored IR

Myocardial mechanics, energetics, and hemodynamics during intraaortic balloon and transvalvular axial flow hemopump support with a bovine model of ischemic cardiac dysfunction.

PubMed

Marks, J D; Pantalos, G M; Long, J W; Kinoshita, M; Everett, S D; Olsen, D B

1999-01-01

Unlike the mechanisms of intraaortic balloon pump (IABP) support, the mechanisms by which transvalvular axial flow Hemopump (HP) support benefit dysfunctional myocardium are less clearly understood. To help elucidate these mechanisms, hemodynamic, metabolic, and mechanical indexes of left ventricular function were measured during conditions of control, ischemic dysfunction, IABP support, and HP support. A large animal (calf) model of left ventricular dysfunction was created with multiple coronary ligations. Peak intraventricular pressure increased with HP support and decreased with IABP support. Intramyocardial pressure (an indicator of intramyocardial stress), time rate of pressure change (an indicator of contractility), and left ventricular myocardial oxygen consumption decreased with IABP and HP support. Left ventricular work decreased with HP support and increased with IABP support. During HP support, indexes of wall stress, work, and contractility, all primary determinants of oxygen consumption, were reduced. During IABP support, indexes of wall stress and contractility were reduced and external work increased. These changes were attributed primarily to changes in ventricular preload, and geometry for HP support, and to a reduction in afterload for IABP support. These findings support the hypothesis that both HP and IABP support reduce intramyocardial stress development and the corresponding oxygen consumption, although via different mechanisms.

Myocardial recovery from ischemia-reperfusion is compromised in the absence of tissue inhibitor of metalloproteinase 4.

PubMed

Takawale, Abhijit; Fan, Dong; Basu, Ratnadeep; Shen, Mengcheng; Parajuli, Nirmal; Wang, Wang; Wang, Xiuhua; Oudit, Gavin Y; Kassiri, Zamaneh

2014-07-01

Myocardial reperfusion after ischemia (I/R), although an effective approach in rescuing the ischemic myocardium, can itself trigger several adverse effects including aberrant remodeling of the myocardium and its extracellular matrix. Tissue inhibitor of metalloproteinases (TIMPs) protect the extracellular matrix against excess degradation by matrix metalloproteinases (MMPs). TIMP4 levels are reduced in myocardial infarction; however, its causal role in progression of post-I/R injury has not been explored. In vivo I/R (20-minute ischemia, 1-week reperfusion) resulted in more severe systolic and diastolic dysfunction in TIMP4(-/-) mice with enhanced inflammation, oxidative stress (1 day post-I/R), hypertrophy, and interstitial fibrosis (1 week). After an initial increase in TIMP4 (1 day post-I/R), TIMP4 mRNA and protein decreased in the ischemic myocardium from wild-type mice by 1 week post-I/R and in tissue samples from patients with myocardial infarction, which correlated with enhanced activity of membrane-bound MMP, membrane-type 1 MMP. By 4 weeks post-I/R, wild-type mice showed no cardiac dysfunction, elevated TIMP4 levels (to baseline), and normalized membrane-type 1 MMP activity. TIMP4-deficient mice, however, showed exacerbated diastolic dysfunction, sustained elevation of membrane-type 1 MMP activity, and worsened myocardial hypertrophy and fibrosis. Ex vivo I/R (20- or 30-minute ischemia, 45-minute reperfusion) resulted in comparable cardiac dysfunction in wild-type and TIMP4(-/-) mice. TIMP4 is essential for recovery from myocardial I/R in vivo, primarily because of its membrane-type 1 MMP inhibitory function. TIMP4 deficiency does not increase susceptibility to ex vivo I/R injury. Replenishment of myocardial TIMP4 could serve as an effective therapy in post-I/R recovery for patients with reduced TIMP4. © 2014 American Heart Association, Inc.

Selective Cerebro-Myocardial Perfusion in Complex Neonatal Aortic Arch Pathology: Midterm Results.

PubMed

Hoxha, Stiljan; Abbasciano, Riccardo Giuseppe; Sandrini, Camilla; Rossetti, Lucia; Menon, Tiziano; Barozzi, Luca; Linardi, Daniele; Rungatscher, Alessio; Faggian, Giuseppe; Luciani, Giovanni Battista

2018-04-01

Aortic arch repair in newborns and infants has traditionally been accomplished using a period of deep hypothermic circulatory arrest. To reduce neurologic and cardiac dysfunction related to circulatory arrest and myocardial ischemia during complex aortic arch surgery, an alternative and novel strategy for cerebro-myocardial protection was recently developed, where regional low-flow perfusion is combined with controlled and independent coronary perfusion. The aim of the present retrospective study was to assess short-term and mid-term results of selective and independent cerebro-myocardial perfusion in neonatal aortic arch surgery. From April 2008 to August 2015, 28 consecutive neonates underwent aortic arch surgery under cerebro-myocardial perfusion. There were 17 male and 11 female, with median age of 15 days (3-30 days) and median body weight of 3 kg (1.6-4.2 kg), 9 (32%) of whom with low body weight (<2.5 kg). The spectrum of pathologies treated was heterogeneous and included 13 neonates having single-stage biventricular repair (46%), 7 staged biventricular repair (25%), and 8 single-ventricle repair (29%). All operations were performed under moderate hypothermia and with a "beating heart and brain." Average cardiopulmonary bypass time was 131 ± 64 min (42-310 min). A period of cardiac arrest to complete intra-cardiac repair was required in nine patients (32%), and circulatory arrest in 1 to repair total anomalous pulmonary venous connection. Average time of splanchnic ischemia during cerebro-myocardial perfusion was 30 ± 11 min (15-69 min). Renal dysfunction, requiring a period of peritoneal dialysis was observed in 10 (36%) patients, while liver dysfunction was noted only in 3 (11%). There were three (11%) early and two late deaths during a median follow-up of 2.9 years (range 6 months-7.7 years), with an actuarial survival of 82% at 7 years. At latest follow-up, no patient showed signs of cardiac or neurologic dysfunction. The present experience

Role of accentuation in the selection/rejection task framing effect.

PubMed

Chen, Jing; Proctor, Robert W

2017-04-01

Procedure invariance is a basic assumption of rational theories of choice, however, it has been shown to be violated: Different response modes, or task frames, sometimes reveal opposite preferences. The current study focused on selection and rejection task frames, involving a unique type of problem with enriched and impoverished options, which has previously led to conflicting findings and theoretical explanations: the compatibility hypothesis (Shafir, 1993) and the accentuation hypothesis (Wedell, 1997). We examined the role of task frame by distinguishing these 2 hypotheses and evaluating the information-processing basis of the choices. Experiments conducted online (Experiments 1 and 3) and in-lab (Experiment 4 with eye-tracking technique) revealed a difference between the 2 task frames in the choice data (i.e., the task-framing effect) as a function of the relative attractiveness of the options. Also, this task-framing effect was not influenced by imposed time constraints (Experiments 5 and 6) and was similarly evident with a more direct measure for the option attractiveness (obtained in Experiment 7). Experiment 2, conducted in a lab setting with verbal-protocol requirements, yielded no task-framing effect, suggesting that a requirement to verbalize reasons for choice minimizes accentuation. With this exception, the choice data are in agreement with the accentuation hypothesis, and the combined findings in choice, decision time, task confusion, and eye-tracking data provide evidence of a basis in cognitive effort rather than motivation, as Wedell proposed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Severe Sepsis and Acute Myocardial Dysfunction in an Adolescent with Chlamydia Trachomatis Pelvic Inflammatory Disease: A Case Report.

PubMed

Morgan, Ashley M; Roden, R Claire; Matson, Steven C; Wallace, Grant M; Lange, Hannah L H; Bonny, Andrea E

2018-04-01

Although generally asymptomatic, severe Chlamydia trachomatis (C. trachomatis) infections have been documented. C. trachomatis has been associated with myocarditis as well as sepsis. A 19-year-old girl with type 1 diabetes mellitus developed sudden-onset mental status change and shock after resolution of diabetic ketoacidosis. Abdominal and pelvic imaging showed uterine and adnexal inflammation, and pelvic examination confirmed a diagnosis of pelvic inflammatory disease. The patient was intubated, required vasopressor support, and developed severe biventricular myocardial dysfunction. Infectious myocarditis workup was negative. Nucleic acid amplification testing from vaginal discharge was positive for C. trachomatis and Trichomonas vaginalis and negative for Neisseria gonorrhoeae. C. trachomatis should be considered in the workup of septic shock, particularly in populations at high risk for sexually transmitted infections. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting

PubMed Central

Heringlake, Matthias; Wernerus, Marit; Grünefeld, Julia; Klaus, Stephan; Heinze, Hermann; Bechtel, Matthias; Bahlmann, Ludger; Poeling, Jochen; Schön, Julika

2007-01-01

Introduction Myocardial dysfunction necessitating inotropic support is a typical complication after on-pump cardiac surgery. This prospective, randomized pilot study analyzes the metabolic and renal effects of the inotropes adrenaline and milrinone in patients needing inotropic support after coronary artery bypass grafting (CABG). Methods During an 18-month period, 251 patients were screened for low cardiac output upon intensive care unit (ICU) admission after elective, isolated CABG surgery. Patients presenting with a cardiac index (CI) of less than 2.2 liters/minute per square meter upon ICU admission – despite adequate mean arterial (titrated with noradrenaline or sodium nitroprusside) and filling pressures – were randomly assigned to 14-hour treatment with adrenaline (n = 7) or milrinone (n = 11) to achieve a CI of greater than 3.0 liters/minute per square meter. Twenty patients not needing inotropes served as controls. Hemodynamics, plasma lactate, pyruvate, glucose, acid-base status, insulin requirements, the urinary excretion of alpha-1-microglobuline, and creatinine clearance were determined during the treatment period, and cystatin-C levels were determined up to 48 hours after surgery (follow-up period). Results After two to four hours after ICU admission, the target CI was achieved in both intervention groups and maintained during the observation period. Plasma lactate, pyruvate, the lactate/pyruvate ratio, plasma glucose, and insulin doses were higher (p < 0.05) in the adrenaline-treated patients than during milrinone or control conditions. The urinary excretion of alpha-1-microglobuline was higher in the adrenaline than in the control group 6 to 14 hours after admission (p < 0.05). No between-group differences were observed in creatinine clearance, whereas plasma cystatin-C levels were significantly higher in the adrenaline than in the milrinone or the control group after 48 hours (p < 0.05). Conclusion This suggests that the use of adrenaline for

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.

Greater Strength Gains after Training with Accentuated Eccentric than Traditional Isoinertial Loads in Already Strength-Trained Men

PubMed Central

Walker, Simon; Blazevich, Anthony J.; Haff, G. Gregory; Tufano, James J.; Newton, Robert U.; Häkkinen, Keijo

2016-01-01

As training experience increases it becomes more challenging to induce further neuromuscular adaptation. Consequently, strength trainers seek alternative training methods in order to further increase strength and muscle mass. One method is to utilize accentuated eccentric loading, which applies a greater external load during the eccentric phase of the lift as compared to the concentric phase. Based upon this practice, the purpose of this study was to determine the effects of 10 weeks of accentuated eccentric loading vs. traditional isoinertial resistance training in strength-trained men. Young (22 ± 3 years, 177 ± 6 cm, 76 ± 10 kg, n = 28) strength-trained men (2.6 ± 2.2 years experience) were allocated to concentric-eccentric resistance training in the form of accentuated eccentric load (eccentric load = concentric load + 40%) or traditional resistance training, while the control group continued their normal unsupervised training program. Both intervention groups performed three sets of 6-RM (session 1) and three sets of 10-RM (session 2) bilateral leg press and unilateral knee extension exercises per week. Maximum force production was measured by unilateral isometric (110° knee angle) and isokinetic (concentric and eccentric 30°.s−1) knee extension tests, and work capacity was measured by a knee extension repetition-to-failure test. Muscle mass was assessed using panoramic ultrasonography and dual-energy x-ray absorptiometry. Surface electromyogram amplitude normalized to maximum M-wave and the twitch interpolation technique were used to examine maximal muscle activation. After training, maximum isometric torque increased significantly more in the accentuated eccentric load group than control (18 ± 10 vs. 1 ± 5%, p < 0.01), which was accompanied by an increase in voluntary activation (3.5 ± 5%, p < 0.05). Isokinetic eccentric torque increased significantly after accentuated eccentric load training only (10 ± 9%, p < 0.05), whereas concentric torque

In vivo Post-Cardiac Arrest Myocardial Dysfunction is Supported by CaMKII-Mediated Calcium Long-Term Potentiation and Mitigated by Alda-1, an Agonist of Aldehyde Dehydrogenase Type 2

PubMed Central

Downey, Peter; Zalewski, Adrian; Rubio, Gabriel R.; Liu, Jing; Homburger, Julian R.; Grunwald, Zachary; Qi, Wei; Bollensdorff, Christian; Thanaporn, Porama; Ali, Ayyaz; Riemer, Kirk; Kohl, Peter; Mochly-Rosen, Daria; Gerstenfeld, Edward; Large, Stephen; Ali, Ziad; Ashley, Euan

2016-01-01

Background Survival after sudden cardiac arrest is limited by post-arrest myocardial dysfunction but understanding of this phenomenon is constrained by lack of data from a physiological model of disease. In this study, we established an in vivo model of cardiac arrest and resuscitation, characterized the biology of the associated myocardial dysfunction, and tested novel therapeutic strategies. Methods We developed rodent models of in vivo post-arrest myocardial dysfunction using extra-corporeal membrane oxygenation (ECMO) resuscitation followed by invasive hemodynamics measurement. In post-arrest isolated cardiomyocytes, we assessed mechanical load and Ca2+ induced Ca2+ release (CICR) simultaneously using the micro-carbon-fiber technique and observed reduced function and myofilament calcium sensitivity. We used a novel-designed fiber optic catheter imaging system, and a genetically encoded calcium sensor GCaMP6f, to image CICR in vivo. Results We found potentiation of CICR in isolated cells from this ECMO model and also in cells isolated from an ischemia-reperfusion Langendorff model perfused with oxygenated blood from an arrested animal, but not when reperfused in saline. We established that CICR potentiation begins in vivo. The augmented CICR observed post-arrest was mediated by the activation of Ca2+/calmodulin kinase II (CaMKII). Increased phosphorylation of CaMKII, phospholamban and ryanodine receptor 2 (RyR2) was detected in the post-arrest period. Exogenous adrenergic activation in vivo recapitulated Ca2+ potentiation but was associated with lesser CaMKII activation. Since oxidative stress and aldehydic adduct formation were high post arrest, we tested a small molecule activator of aldehyde dehydrogenase type 2, Alda-1, which reduced oxidative stress, restored calcium and CaMKII homeostasis, and improved cardiac function and post-arrest outcome in vivo. Conclusions Cardiac arrest and reperfusion lead to CaMKII activation and calcium long-term potentiation

Diastolic dysfunction in hypertension.

PubMed

Nazário Leão, R; Marques da Silva, P

Hypertension and coronary heart disease, often coexisting, are the most common risk factors for heart failure. The progression of hypertensive heart disease involves myocardial fibrosis and alterations in the left ventricular geometry that precede the functional change, initially asymptomatic. The left ventricular diastolic dysfunction is part of this continuum being defined by the presence of left ventricular diastolic dysfunction without signs or symptoms of heart failure or poor left ventricular systolic function. It is highly prevalent in hypertensive patients and is associated with increased cardiovascular morbidity and mortality. Despite its growing importance in clinical practice it remains poorly understood. This review aims to present the epidemiological fundamentals and the latest developments in the pathophysiology, diagnosis and treatment of left ventricular diastolic dysfunction. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Coronary microvascular dysfunction in diabetes mellitus

PubMed Central

Selthofer-Relatic, Kristina; Drenjancevic, Ines; Bacun, Tatjana; Bosnjak, Ivica; Kibel, Dijana; Gros, Mario

2017-01-01

The significance, mechanisms and consequences of coronary microvascular dysfunction associated with diabetes mellitus are topics into which we have insufficient insight at this time. It is widely recognized that endothelial dysfunction that is caused by diabetes in various vascular beds contributes to a wide range of complications and exerts unfavorable effects on microcirculatory regulation. The coronary microcirculation is precisely regulated through a number of interconnected physiological processes with the purpose of matching local blood flow to myocardial metabolic demands. Dysregulation of this network might contribute to varying degrees of pathological consequences. This review discusses the most important findings regarding coronary microvascular dysfunction in diabetes from pre-clinical and clinical perspectives. PMID:28643578

Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling.

PubMed

Moro, Cécile; Jouan, Marie-Gabrielle; Rakotovao, Andry; Toufektsian, Marie-Claire; Ormezzano, Olivier; Nagy, Norbert; Tosaki, Arpad; de Leiris, Joël; Boucher, François

2007-11-01

Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-alpha occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-alpha can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3alpha was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling.

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)

PubMed Central

Yu, Xichun; Tesiram, Yasvir A; Towner, Rheal A; Abbott, Andrew; Patterson, Eugene; Huang, Shijun; Garrett, Marion W; Chandrasekaran, Suresh; Matsuzaki, Satoshi; Szweda, Luke I; Gordon, Brian E; Kem, David C

2007-01-01

Background Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. Methods Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19–25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls. Results After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. Conclusion Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy. PMID:17309798

Assessment of left ventricular myocardial deformation by cardiac MRI strain imaging reveals myocardial dysfunction in patients with primary cardiac tumors.

PubMed

Chen, Jing; Yang, Zhi-Gang; Xu, Hua-Yan; Shi, Ke; Guo, Ying-Kun

2018-02-15

To assess left ventricular myocardial deformation in patients with primary cardiac tumors. MRI was retrospectively performed in 61 patients, including 31 patients with primary cardiac tumors and 30 matched normal controls. Left ventricular strain and function parameters were then assessed by MRI-tissue tracking. Differences between the tumor group and controls, left and right heart tumor groups, left ventricular wall tumor and non-left ventricular wall tumor groups, and tumors with and without LV enlargement groups were assessed. Finally, the correlations among tumor diameter, myocardial strain, and LV function were analyzed. Left ventricular myocardial strain was milder for tumor group than for normal group. Peak circumferential strain (PCS) and its diastolic strain rate, longitudinal strains (PLS) and its diastolic strain rates, and peak radial systolic and diastolic velocities of the right heart tumor group were lower than those of the left heart tumor group (all p<0.050), but the peak radial systolic strain rate of the former was higher than that of the latter (p=0.017). The corresponding strains were lower in the left ventricular wall tumor groups than in the non-left ventricular wall tumor group (p<0.050). Peak radial systolic velocities were generally higher for tumors with LV enlargement than for tumors without LV enlargement (p<0.050). Peak radial strain, PCS, and PLS showed important correlations with the left ventricular ejection fraction (all p<0.050). MRI-tissue tracking is capable of quantitatively assessing left ventricular myocardial strain to reveal sub-clinical abnormalities of myocardial contractile function. Copyright © 2017 Elsevier B.V. All rights reserved.

Perioperative Assessment of Myocardial Deformation

PubMed Central

Duncan, Andra E.; Alfirevic, Andrej; Sessler, Daniel I.; Popovic, Zoran B.; Thomas, James D.

2014-01-01

assess components of myocardial systolic and diastolic function. Myocardial deformation analysis is based on either Doppler or a non-Doppler technique, called speckle-tracking echocardiography. Myocardial deformation analysis provides quantitative measures of global and regional myocardial function for use in the perioperative care of the surgical patient. For example, coronary graft occlusion after coronary artery bypass grafting is detected by an acute reduction in strain in the affected coronary artery territory. In addition, assessment of left ventricular mechanics detects underlying myocardial pathology before abnormalities become apparent on conventional echocardiography. Certainly, patients with aortic regurgitation demonstrate reduced longitudinal strain before reduction in LVEF occurs, which allows detection of subclinical left ventricular dysfunction and predicts increased risk for heart failure and impaired myocardial function after surgical repair. In this review we describe the principles, techniques, and clinical application of myocardial deformation analysis. PMID:24557101

The accentuation principle of figure-ground segregation and the downbeat illusion.

PubMed

Pinna, Baingio; Sirigu, Luca

2016-10-01

Pinna and Sirigu (2011) demonstrated a new principle of grouping, called the accentuation principle, stating that, all else being equal, elements tend to group in the same oriented direction of the discontinuous element placed within a whole set of continuous/homogeneous components. The discontinuous element behaves like an accent, i.e. a visual emphasis within the wholeness of components as shown in the next section. In this work, the accentuation principle has been extended to new visual domains. In particular, it is shown how this principle affects shape perception. Moreover several visual object attributes are also highlighted, among which orientation, spatial position, inner dynamics and apparent motion that determine the so-called organic segmentation and furthermore tend to induce figure-ground segregation. On the basis of the results of experimental phenomenology, the accentuation can be considered as a complex principle ruling grouping, figure-ground segregation, shape and meaning formation. Through a new musical illusion of downbeat, it is also demonstrated that this principle influences perceptual organization not only in space but also in time and, thus, in both visual and musical domains. This illusion can be heard in eight measures of Pagodes, a solo piano music by Claude Debussy (1862-1918), where a strong physical-perceptual discrepancy in terms of upbeats and downbeats inversion is strongly perceived in both staves. Copyright © 2016 Elsevier B.V. All rights reserved.

Xanthine Oxidase Inhibition with Febuxostat Attenuates Systolic Overload-induced Left Ventricular Hypertrophy and Dysfunction in Mice

PubMed Central

Xu, Xin; Hu, Xinli; Lu, Zhongbing; Zhang, Ping; Zhao, Lin; Wessale, Jerry L.; Bache, Robert J.; Chen, Yingjie

2008-01-01

The purine analog xanthine oxidase (XO) inhibitors (XOIs), allopurinol and oxypurinol, have been reported to protect against heart failure secondary to myocardial infarction or rapid ventricular pacing. Since these agents might influence other aspects of purine metabolism that could influence their effect, this study examined the effect of the non-purine XOI, febuxostat, on pressure overload-induced left ventricular (LV) hypertrophy and dysfunction. Transverse aortic constriction (TAC) in mice caused LV hypertrophy and dysfunction as well as increased myocardial nitrotyrosine at 8 days. TAC also caused increased phosphorylated Akt (p-AktSer473), p42/44 extracellular signal-regulated kinase (p-ErkThr202/Tyr204) and mammalian target of rapamycin (mTOR) (p-mTORSer2488). XO inhibition with febuxostat (5mg/kg/day by gavage for 8 days) beginning ~60 minutes after TAC attenuated the TAC-induced LV hypertrophy and dysfunction. Febuxostat blunted the TAC-induced increases in nitrotyrosine (indicating reduced myocardial oxidative stress), p-ErkThr202/Tyr204 and p-mTORSer2488, with no effect on total Erk or total mTOR. Febuxostat had no effect on myocardial p-AktSer473 or total Akt. The results suggest that XO inhibition with febuxostat reduced oxidative stress in the pressure overloaded LV, thereby diminishing the activation of pathways that result in pathologic hypertrophy and contractile dysfunction. PMID:18995179

Functional Cardiac Magnetic Resonance Imaging (MRI) in the Assessment of Myocardial Viability and Perfusion

PubMed Central

2003-01-01

Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness safety and cost-effectiveness of using functional cardiac magnetic resonance imaging (MRI) for the assessment of myocardial viability and perfusion in patients with coronary artery disease and left ventricular dysfunction. Results Functional MRI has become increasingly investigated as a noninvasive method for assessing myocardial viability and perfusion. Most patients in the published literature have mild to moderate impaired LV function. It is possible that the severity of LV dysfunction may be an important factor that can alter the diagnostic accuracy of imaging techniques. There is some evidence of comparable or better performance of functional cardiac MRI for the assessment of myocardial viability and perfusion compared with other imaging techniques. However limitations to most of the studies included: Functional cardiac MRI studies that assess myocardial viability and perfusion have had small sample sizes. Some studies assessed myocardial viability/perfusion in patients who had already undergone revascularization, or excluded patients with a prior MI (Schwitter et al., 2001). Lack of explicit detail of patient recruitment. Patients with LVEF >35%. Interstudy variability in post MI imaging time(including acute or chronic MI), when patients with a prior MI were included. Poor interobserver agreement (kappa statistic) in the interpretation of the results. Traditionally, 0.80 is considered “good”. Cardiac MRI measurement of myocardial perfusion to as an adjunct tool to help diagnose CAD (prior to a definitive coronary angiography) has also been examined in some studies, with methodological limitations, yielding comparable results. Many studies examining myocardial viability and perfusion report on the accuracy of imaging methods with limited data on long-term patient outcome and management. Kim et al. (2000) revealed that the transmural

Myocardial oxygen delivery after experimental hemorrhagic shock.

PubMed Central

Archie, J P; Mertz, W R

1978-01-01

The two components of myocardial oxygen delivery, coronary blood flow to capillaries and diffusion from capillaries to mitochondria, were studied in six dogs, (1) prior to shock, (2) after three hours of hemorrhage shock at a mean systemic arterial pressure of 40 torr, (3) after reinfusion of shed blood, and (4) during the irreversible late posttransfusion stage. There was a maldistribution of left ventricular coronary flow during late shock consistent with subendocardial ischemia. Cardiac performance was significantly impaired after resuscitation and all dogs became irreversible. Total and regional left ventricular coronary blood flow and myocardial oxygen delivery to capillaries were significantly greater than preshock values in (3) but not different from preshock values in (4). However, the myocardial oxygen diffusion area to distance ratio was significantly lower than preshock values in (3), and slightly lower in (4). These data suggest that myocardial oxygen diffusion may be impaired in the early post transfusion period, (3). Accordingly, the probable etiology of left ventricular dysfunction and possibly irreversibility after resuscitation from hemorrhagic shock is subendocardial ischemia during shock with either post-resuscitation impairment of myocardial oxygen diffusion, or in cellular oxygen utilization, or both. PMID:629622

Finland Has it All? Examining the Media Accentuation of "Finnish Education" in Australia, Germany and South Korea

ERIC Educational Resources Information Center

Takayama, Keita; Waldow, Florian; Sung, Youl-Kwan

2013-01-01

Drawing on the conceptual work of externalisation in comparative education and multi-accentual signs in cultural studies, this article examines how the print news media accentuate "Finnish education" in the process of inserting this external reference into the domestic political discourses around education reform in Australia, Germany…

Modern nuclear cardiac imaging in diagnosis and clinical management of patients with left ventricular dysfunction.

PubMed

Abidov, A; Hachamovitch, R; Berman, D S

2004-12-01

Congestive heart failure (CHF) has become a large social burden in modern Western society, with very high morbidity and mortality and extremely large financial costs. The largest cause of CHF is coronary heart disease, with ventricular dysfunction that may or may not be reversible by revascularization. Thus, evaluation of the viable myocardial tissue in patients with ischemic left ventricular (LV) dysfunction has important clinical and therapeutic implications. Furthermore, since patients with ventricular dysfunction are at higher operative risk, cardiologists and cardiac surgeons are commonly faced with issues regarding the balance between the potential risk vs benefit of revascularization procedures. Cardiac nuclear imaging [myocardial perfusion SPECT (MPS) and positron emission tomography (PET)] provide objective information that augments standard clinical and angiographic assessments of patients with ventricular dysfunction with respect to diagnosis (etiology), prognosis, and potential benefit from intervention. Development of the technology and methodology of gated MPS, now the routine method for MPS, allows assessment of the extent and severity of inducible ischemia as well as hypoperfused but viable myocardium, and also provides measurements of LV ejection fraction, regional wall motion, LV volume measurements, diastolic function and LV geometry. With PET, myocardial metabolism and blood flow reserve can be added to the measurements provided by nuclear cardiology procedures. This paper provides insight into the current evidence regarding settings in which nuclear cardiac imaging procedures are helpful in assessment of patients in the setting of coronary artery disease with severe LV dysfunction. A risk-benefit approach to MPS results is proposed, with principal focus on identifying patients at risk for major cardiac events who may benefit from myocardial revascularization.

Chronic Kidney Disease Exacerbates Myocardial Ischemia Reperfusion Injury: Role of Endoplasmic Reticulum Stress-Mediated Apoptosis.

PubMed

Guo, Junjie; Zhu, Jianbing; Ma, Leilei; Shi, Hongtao; Hu, Jiachang; Zhang, Shuning; Hou, Lei; Xu, Fengqiang; An, Yi; Yu, Haichu; Ge, Junbo

2018-06-01

Chronic kidney disease (CKD) is known to exacerbate myocardial ischemia reperfusion (IR) injury. However, the underlying mechanisms are still not well understood. Despite various strategies for cardioprotection, limited studies have been focused on the prevention of CKD-induced myocardial susceptibility to IR injury. Here, we hypothesized that excessive endoplasmic reticulum (ER) stress-mediated apoptosis involved in myocardial IR injury in CKD mice and pretreatment with chemical ER chaperone rendered the heart resistant to myocardial IR injury in the setting of CKD. CKD was induced by 5/6 subtotal nephrectomy (SN) in mice, whereas sham-operated mice served as control (Sham). CKD significantly aggravated the cardiac injury after IR in SN group than Sham group as reflected by more severe cardiac dysfunction, increased myocardial infarct size and the ratio of myocardial apoptosis. The expression of ER stress-mediated apoptotic proteins (Bcl-2 associated X protein (Bax), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12) was markedly upregulated after IR injury in SN group than Sham group, whereas the expression of anti-apoptotic protein, Bcl-2, was obviously downregulated. In addition, the chemical ER chaperone sodium 4-phenylbutyrate (4PBA) pretreatment ameliorated cardiac dysfunction and lessened the infarct size and myocardial apoptosis after IR injury in mice with CKD. Taken together, these findings demonstrated that excessive activation of ER stress-mediated apoptosis pathway involved in the CKD-induced myocardial susceptibility to IR injury, and chemical ER chaperone 4PBA alleviated myocardial IR injury in mice with CKD.

Role of myocardial collagen degradation and fibrosis in right ventricle dysfunction in transposition of the great arteries after atrial switch.

PubMed

Ladouceur, Magalie; Baron, Stephanie; Nivet-Antoine, Valérie; Maruani, Gérard; Soulat, Gilles; Pereira, Helena; Blanchard, Anne; Boutouyrie, Pierre; Paul, Jean Louis; Mousseaux, Elie

2018-05-01

Heart failure is a serious event in patients with transposition of the great arteries (D-TGA) after atrial redirection surgery. We aimed to determine the association between myocardial fibrosis and systolic and diastolic systemic right ventricle (sRV) dysfunction. Diastolic and systolic function of sRV was prospectively assessed using echocardiography and cardiac magnetic resonance imaging (CMR) in 48 patients with atrially switched D-TGA and 26 healthy subjects. Diastolic function of the subaortic ventricle was assessed by echocardiography Doppler and DTI. In CMR, ejection fraction of sRV and wall stress defined as the product of the systolic blood pressure and volume/mass ratio were assessed. Fibrosis extent within sRV myocardium was evaluated using gadolinium-enhanced magnetic resonance and serum collagen turnover biomarkers. Late gadolinium enhancement (LGE) was found in 35% of D-TGA patients, and the collagen degradation biomarker pro-MMP1:TIMP1 ratio was significantly increased in D-TGA patients compared to healthy subjects (1.0 × 10 -2 vs. 2.5 × 10 -2 , p = 0.04). Increase in sRV wall stress was significantly associated with LGE (p = 0.01) and pro-MMP1:TIMP1 ratio (r = 0.77, p < 0.01). After adjustment for age, sex, BMI, blood pressure and cardiac treatment, pro-MMP1:TIMP1 ratio was the strongest determinant of sRVEF (R 2  = 0.85, p < 0.01). Pro-MMP1:TIMP1 ratio was also significantly correlated with the early diastolic filling parameter E/E' (r = 0.53, p = 0.02), but this was not anymore the case after adjustment. Diastolic and systolic sRV dysfunction is related to myocardial collagen degradation and fibrosis. Research in medical therapies that reduce systemic sRV afterload and limit collagen degradation is warranted in this setting. Copyright © 2018 Elsevier B.V. All rights reserved.

Targeted Imaging of the Spatial and Temporal Variation of Matrix Metalloproteinase Activity in Porcine Model of Post-Infarct Remodeling: Relationship to Myocardial Dysfunction

PubMed Central

Sahul, Zakir H.; Mukherjee, Rupak; Song, James; McAteer, Jarod; Stroud, Robert E.; Dione, Donald P.; Staib, Lawrence; Papademetris, Xenophon; Dobrucki, Lawrence W.; Duncan, James S.; Spinale, Francis G.; Sinusas, Albert J.

2011-01-01

Background Matrix metalloproteinases (MMPs) are known to modulate left ventricular (LV) remodeling after a myocardial infarction (MI). However, the temporal and spatial variation of MMP activation and their relationship to mechanical dysfunction post MI remains undefined. Methods and Results MI was surgically induced in pigs (n=23) and cine MR and dual isotope hybrid SPECT/CT imaging obtained using thallium-201 (201Tl) and a technetium-99m labeled MMP targeted tracer (99mTc-RP805) at 1, 2 and 4 weeks post MI along with controls (n=5). Regional myocardial strain was computed from MR images and related to MMP zymography and ex vivo myocardial 99mTc-RP805 retention. MMP activation as assessed by in vivo and ex vivo 99mTc-RP805 imaging/retention studies was increased nearly 5-fold within the infarct region at 1 week post-MI and remained elevated up to 1 month post-MI. The post-MI change in LV end-diastolic volumes was correlated with MMP activity (y=31.34e0.48x, p=0.04). MMP activity was increased within the border and remote regions early post-MI, but declined over 1 month. There was a high concordance between regional 99mTc-RP805 uptake and ex vivo MMP-2 activity. Conclusions A novel, multimodality non-invasive hybrid SPECT/CT imaging approach was validated and applied for in vivo evaluation of MMP activation in combination with cine MR analysis of LV deformation. Increased 99mTc-RP805 retention was seen throughout the heart early post-MI and was not purely a reciprocal of 201Tl perfusion. 99mTc-RP805 SPECT/CT imaging may provide unique information regarding regional myocardial MMP activation and predict late post-MI LV remodeling. PMID:21505092

Hypercholesterolemia and Myocardial function evaluated via Tissue Doppler Imaging

PubMed Central

2009-01-01

Objective To establish a link between hypercholesterolemia and myocardial dysfunction. Background Heart failure is a complex disease involving changes in systolic and diastolic function. Newer echocardiographic imaging modalities may be able to detect discreet changes in myocardial function associated with hypercholesterolemia. Therefore we sought to establish a link between hypercholesterolemia and myocardial dysfunction with tissue Doppler imaging (TDI). Methods Twenty-seven rabbits were studied: 7 were fed normal chow (group 1) and 20 a high cholesterol diet (10 with ezetimibe, 1 mg/kg/day; group 2 and 10 without, group 3). Echocardiographic images were obtained under general anesthesia. Serum cholesterol levels were obtained at baseline, 3 and 6 months and myocardial cholesterol levels measured following euthanasia. Results Doppler measurements, including E/A, E'/A' and S' were significantly lower in group 3 compared to both groups 1 and 2 but no significant differences were noted in chamber sizes or ejection fraction among the groups. Average serum cholesterol was higher in group 3 compared to groups 1 and 2 respectively (495 ± 305 mg/dl vs. 114 ± 95 mg/dl and 87 ± 37 mg/dl; p < 0.01). Myocardial cholesterol content was also higher in group 3 compared to group 2 (0.10 ± 0.04 vs. 0.06 mg/dl ± 0.02; p = 0.05). There was significant correlation between S', E'/A', E/E' and serum cholesterol (r2 = 0.17 p = 0.04, r2 = 0.37 p = 0.001 and r2 = 0.24 p = 0.01). Conclusion Cholesterol load in the serum and myocardium was significantly associated with decreased systolic and diastolic function by TDI. Moreover, lipid lowering was protective. PMID:19943937

Right ventricular myocardial infarction: presentation and acute outcomes.

PubMed

Chockalingam, Anand; Gnanavelu, G; Subramaniam, T; Dorairajan, Smrita; Chockalingam, V

2005-01-01

Acute inferior wall myocardial infarction can be complicated by right ventricular myocardial infarction (RVMI), and the excess mortality cannot be fully explained by mechanical reasons. The authors try to systematically assess the incidence, clinical presentation and early outcomes of right ventricular infarction in a tertiary-care setup. Their study was a prospective observational series of consecutive patients with RVMI. All patients with acute inferior myocardial infarction (n=135) were enlisted. RVMI was diagnosed by > or = 1 mm ST elevation in lead V(4R) in a right-sided electrocardiogram. Right ventricular (RV) infarction occurred in 37% (n=50) of patients with acute inferior infarctions. Patients with isolated inferior infarction served as controls (n=85). Echocardiography was performed within 24 hours of admission. From both groups, 66% qualified for thrombolysis. The incidence of hypotension-bradycardia and heart blocks requiring pacing support was much higher in right ventricular infarction (n=21) than in inferior infarction (n=13). Clinically manifest RV dysfunction (raised jugular venous pulse [JVP], hypotension, tricuspid regurgitation) and right ventricular dilation detected by echocardiography were seen in only 13 patients. The in-hospital mortality rate was significantly higher (n=8, 16%) in right ventricular infarction group than in inferior infarction group (n=3, 3.5%). Right ventricular infarction was seen in a third of inferior myocardial infarctions (IMIs), but hemodynamically evident right ventricular dysfunction occurred in only a tenth of acute IMIs. Nevertheless, the acute in-hospital mortality rate of patients with right ventricular infarction was much higher than in those with inferior infarction owing to arrhythmic and mechanical complications.

Pre- and postconditioning effect of Sevoflurane on myocardial dysfunction after cardiopulmonary resuscitation in rats.

PubMed

Knapp, Jürgen; Bergmann, Greta; Bruckner, Thomas; Russ, Nicolai; Böttiger, Bernd W; Popp, Erik

2013-10-01

Post-resuscitation myocardial dysfunction is an important cause of death in the intensive care unit after initially successful cardiopulmonary resuscitation (CPR) of pre-hospital cardiac arrest (CA) patients. Volatile anaesthetics reduce ischaemic-reperfusion injury in regional ischaemia in beating hearts. This effect, called anaesthetic-induced pre- or postconditioning, can be shown when the volatile anaesthetic is given either before regional ischaemia or in the reperfusion phase. However, up to now, little data exist for volatile anaesthetics after global ischaemia due to CA. Therefore, the goal of this study was to clarify whether Sevoflurane improves post-resuscitation myocardial dysfunction after CA in rats. Following institutional approval by the Governmental Animal Care Committee, 144 male Wistar rats (341±19g) were randomized either to a control group or to one of the 9 interventional groups receiving 0.25 MAC, 0.5 MAC or 1 MAC of Sevoflurane for 5min either before resuscitation (SBR), during resuscitation (SDR) or after resuscitation (SAR). After 6min of electrically induced ventricular fibrillation CPR was performed. Before CA (baseline) as well as 1h and 24h after restoration of spontaneous circulation (ROSC), continuous measurement of ejection fraction (EF), and preload adjusted maximum power (PAMP) as primary outcome parameters and end systolic pressure (ESP), end diastolic volume (EDV) and maximal slope of systolic pressure increment (dP/dtmax) as secondary outcome parameters was performed using a conductance catheter. EF was improved in all Sevoflurane treated groups 1h after ROSC in comparison to control, except for the 0.25 MAC SDR and 0.25 MAC SAR group (0.25 MAC SBR: 38±8, p=0.02; 0.5 MAC SBR: 39±7, p=0.04; 1 MAC SBR: 40±6, p=0.007; 0.5 MAC SDR: 38±7, p=0.02; 1 MAC SDR: 40±6, p=0.006; 0.5 MAC SAR: 39±6, p=0.01; 1 MAC SAR: 39±6, p=0.002, vs. 30±7%). Twenty-four hours after ROSC, EF was higher than control in all interventional groups (p

Diastolic dysfunction in the critically ill patient.

PubMed

Suárez, J C; López, P; Mancebo, J; Zapata, L

2016-11-01

Left ventricular diastolic dysfunction is a common finding in critically ill patients. It is characterized by a progressive deterioration of the relaxation and the compliance of the left ventricle. Two-dimensional and Doppler echocardiography is a cornerstone in its diagnosis. Acute pulmonary edema associated with hypertensive crisis is the most frequent presentation of diastolic dysfunction critically ill patients. Myocardial ischemia, sepsis and weaning failure from mechanical ventilation also may be associated with diastolic dysfunction. The treatment is based on the reduction of pulmonary congestion and left ventricular filling pressures. Some studies have found a prognostic role of diastolic dysfunction in some diseases such as sepsis. The present review aims to analyze thoroughly the echocardiographic diagnosis and the most frequent scenarios in critically ill patients in whom diastolic dysfunction plays a key role. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

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.

Interleukin-6 Mediates Myocardial Fibrosis, Concentric Hypertrophy and Diastolic Dysfunction in Rats

PubMed Central

Meléndez, Giselle C.; McLarty, Jennifer L.; Levick, Scott P.; Du, Yan; Janicki, Joseph S.; Brower, Gregory L.

2010-01-01

While there is a correlation between hypertension and levels of IL-6, the exact role of this cytokine in myocardial remodeling is unknown. This is complicated by the variable tissue and circulating levels of IL-6 reported in numerous experimental models of hypertension. Accordingly, we explored the hypothesis that elevated levels of IL-6 mediate adverse myocardial remodeling. To this end, adult male Sprague Dawley rats were infused with IL-6 (2.5 μg·kg-1·hr-1, IP) for 7 days via osmotic minipump and compared to vehicle infused aged-matched controls. Left ventricular function was evaluated using a blood-perfused isolated heart preparation. In addition, myocardial interstitial collagen volume fraction and isolated cardiomyocyte size were also assessed. Isolated adult cardiac fibroblast experiments were performed to determine the importance of the soluble IL-6 receptor in mediating cardiac fibrosis. IL-6 infusions in vivo resulted in concentric left ventricular hypertrophy, increased ventricular stiffness, a marked increase in collagen volume fraction (6.2 vs. 1.7%; p < 0.001), and proportional increases in cardiomyocyte width and length; all independent of blood pressure. The soluble IL-6 receptor in combination with IL-6 was found to be essential in increasing collagen content regulated by isolated cardiac fibroblasts, and also played a role in mediating a phenotypic conversion to myofibroblasts. These novel observations demonstrate that IL-6 induces a myocardial phenotype almost identical to that of the hypertensive heart, identifying IL-6 as potentially important in this remodeling process. PMID:20606113

Acute Right Ventricular Dysfunction in Intensive Care Unit

PubMed Central

Domingo, Enric

2017-01-01

The role of the left ventricle in ICU patients with circulatory shock has long been considered. However, acute right ventricle (RV) dysfunction causes and aggravates many common critical diseases (acute respiratory distress syndrome, pulmonary embolism, acute myocardial infarction, and postoperative cardiac surgery). Several supportive therapies, including mechanical ventilation and fluid management, can make RV dysfunction worse, potentially exacerbating shock. We briefly review the epidemiology, pathophysiology, diagnosis, and recommendations to guide management of acute RV dysfunction in ICU patients. Our aim is to clarify the complex effects of mechanical ventilation, fluid therapy, vasoactive drug infusions, and other therapies to resuscitate the critical patient optimally. PMID:29201914

Nitroglycerin Use in Myocardial Infarction Patients: Risks and Benefits

PubMed Central

Ferreira, Julio C.B.; Mochly-Rosen, Daria

2012-01-01

Acute myocardial infarction and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin remains a first-line treatment for angina pectoris and acute myocardial infarction. Nitroglycerin achieves its benefit by giving rise to nitric oxide, which causes vasodilation and increases blood flow to the myocardium. However, continuous delivery of nitroglycerin results in tolerance, limiting the use of this drug. Nitroglycerin tolerance is due, at least in part, to inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme that converts nitroglycerin to the vasodilator, nitric oxide. We have recently found that, in addition to nitroglycerin’s effect on the vasculature, sustained treatment with nitroglycerin negatively affects cardiomyocyte viability following ischemia, thus resulting in increased infarct size in a myocardial infarction model in animals. Co-administration of Alda-1, an activator of ALDH2, with nitroglycerin improves metabolism of reactive aldehyde adducts and prevents the nitroglycerin-induced increase in cardiac dysfunction following myocardial infarction. In this review, we describe the molecular mechanisms associated with the benefits and risks of nitroglycerin administration in myocardial infarction. (167 of 200). PMID:22040938

Endocannabinoids as mediators in the heart: a potential target for therapy of remodelling after myocardial infarction?

PubMed Central

Hiley, C Robin; Ford, William R

2003-01-01

Endocannabinoid production by platelets and macrophages is increased in circulatory shock. This may be protective of the cardiovascular system as blockade of CB1 cannabinoid receptors exacerbates endothelial dysfunction in haemorrhagic and endotoxin shock and reduces survival. Now evidence suggests that blockade of CB1 receptors starting 24 h after myocardial infarction in rats has a deleterious effect on cardiac performance, while use of a nonselective cannabinoid receptor agonist prevents hypotension and reduces endothelial dysfunction, although left ventricular end diastolic pressure is elevated. Cannabinoids and endocannabinoid systems may therefore present useful targets for therapy following myocardial infarction. PMID:12711614

The immune system and the remodeling infarcted heart: cell biological insights and therapeutic opportunities

PubMed Central

Frangogiannis, Nikolaos G

2014-01-01

Extensive necrosis of ischemic cardiomyocytes in the infarcted myocardium activates the innate immune response triggering an intense inflammatory reaction. Release of danger signals from dying cells and damaged matrix activates the complement cascade and stimulates Toll-Like Receptor (TLR)/Interleukin (IL)-1 signaling, resulting in activation of the Nuclear Factor (NF)-κB system and induction of chemokines, cytokines and adhesion molecules. Subsequent infiltration of the infarct with neutrophils and mononuclear cells serves to clear the wound from dead cells and matrix debris, while stimulating reparative pathways. In addition to its role in repair of the infarcted heart and formation of a scar, the immune system is also involved in adverse remodeling of the infarcted ventricle. Overactive immune responses and defects in suppression, containment and resolution of the post-infarction inflammatory reaction accentuate dilative remodeling in experimental models and may be associated with chamber dilation, systolic dysfunction and heart failure in patients surviving a myocardial infarction. Interventions targeting the inflammatory response to attenuate adverse remodeling may hold promise in patients with myocardial infarction that exhibit accentuated, prolonged, or dysregulated immune responses to the acute injury. PMID:24072174

Heart involvement in cystic fibrosis: A specific cystic fibrosis-related myocardial changes?

PubMed

Labombarda, Fabien; Saloux, Eric; Brouard, Jacques; Bergot, Emmanuel; Milliez, Paul

2016-09-01

Cystic fibrosis is a complex multi-systemic chronic disease characterized by progressive organ dysfunction with development of fibrosis, possibly affecting the heart. Over the last four decades pathological, experimental, and clinical evidence points towards the existence of a specific myocardial involvement in cystic fibrosis. Multi-modality cardiac imaging, especially recent echocardiographic techniques, evidenced diastolic and/or systolic ventricular dysfunction in cystic fibrosis leading to the concept of a cystic fibrosis-related cardiomyopathy. Hypoxemia and inflammation are among the most important factors for heart involvement in cystic fibrosis. Cystic Fibrosis Transmembrane Regulator was found to be involved in the regulation of cardiomyocyte contraction and may also account for cystic fibrosis-related myocardial dysfunction. This review, mainly focused on echocardiographic studies, seeks to synthesize the existing literature for and against the existence of heart involvement in cystic fibrosis, its mechanisms and prognostic implications. Careful investigation of the heart function may be helpful for risk stratification and therapeutic decisions in patients with cystic fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Myocardial Viability and Impact of Surgical Ventricular Reconstruction on Outcomes of Patients with Severe Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Surgery: Results of the Surgical Treatment for Ischemic Heart Failure (STICH) Trial

PubMed Central

Holly, Thomas A.; Bonow, Robert O.; Arnold, J. Malcolm O.; Oh, Jae K.; Varadarajan, Padmini; Pohost, Gerald M.; Haddad, Haissam; Jones, Robert H.; Velazquez, Eric J.; Birkenfeld, Bozena; Asch, Federico M.; Malinowski, Marcin; Barretto, Rodrigo; Kalil, Renato A.K.; Berman, Daniel S.; Sun, Jie-Lena; Lee, Kerry L.; Panza, Julio A.

2014-01-01

Objective In the Surgical Treatment for Ischemic Heart Failure (STICH) trial, surgical ventricular reconstruction plus coronary artery bypass surgery was not associated with a reduction in the rate of death or cardiac hospitalization compared to bypass alone. We hypothesized that the absence of viable myocardium identifies patients with coronary artery disease and left ventricular dysfunction who have a greater benefit with coronary artery bypass graft surgery and surgical ventricular reconstruction compared to bypass alone. Methods Myocardial viability was assessed by single photon computed tomography in 267 of the 1,000 patients randomized to bypass or bypass plus surgical ventricular reconstruction in STICH. Myocardial viability was assessed on a per patient basis as well as regionally based on pre-specified criteria. Results At 3 years, there was no difference in mortality or the combined outcome of death or cardiac hospitalization between those with and those without viability, and there was no significant interaction between the type of surgery and global viability status with respect to mortality or death plus cardiac hospitalization. Furthermore, there was no difference in mortality or death plus cardiac hospitalization between those with and without anterior wall or apical scar, and no significant interaction between the presence of scar in these regions and the type of surgery with respect to mortality. Conclusion In patients with coronary artery disease and severe regional left ventricular dysfunction, assessment of myocardial viability does not identify patients who will derive a mortality benefit from adding surgical ventricular reconstruction to coronary artery bypass graft surgery. PMID:25152476

Synergistic role of ADP and Ca2+ in diastolic myocardial stiffness

PubMed Central

Sequeira, Vasco; Najafi, Aref; McConnell, Mark; Fowler, Ewan D; Bollen, Ilse A E; Wüst, Rob C I; dos Remedios, Cris; Helmes, Michiel; White, Ed; Stienen, Ger J M; Tardiff, Jil; Kuster, Diederik W D; van der Velden, Jolanda

2015-01-01

Abstract Heart failure (HF) with diastolic dysfunction has been attributed to increased myocardial stiffness that limits proper filling of the ventricle. Altered cross-bridge interaction may significantly contribute to high diastolic stiffness, but this has not been shown thus far. Cross-bridge interactions are dependent on cytosolic [Ca2+] and the regeneration of ATP from ADP. Depletion of myocardial energy reserve is a hallmark of HF leading to ADP accumulation and disturbed Ca2+ handling. Here, we investigated if ADP elevation in concert with increased diastolic [Ca2+] promotes diastolic cross-bridge formation and force generation and thereby increases diastolic stiffness. ADP dose-dependently increased force production in the absence of Ca2+ in membrane-permeabilized cardiomyocytes from human hearts. Moreover, physiological levels of ADP increased actomyosin force generation in the presence of Ca2+ both in human and rat membrane-permeabilized cardiomyocytes. Diastolic stress measured at physiological lattice spacing and 37°C in the presence of pathological levels of ADP and diastolic [Ca2+] revealed a 76 ± 1% contribution of cross-bridge interaction to total diastolic stress in rat membrane-permeabilized cardiomyocytes. Inhibition of creatine kinase (CK), which increases cytosolic ADP, in enzyme-isolated intact rat cardiomyocytes impaired diastolic re-lengthening associated with diastolic Ca2+ overload. In isolated Langendorff-perfused rat hearts, CK inhibition increased ventricular stiffness only in the presence of diastolic [Ca2+]. We propose that elevations of intracellular ADP in specific types of cardiac disease, including those where myocardial energy reserve is limited, contribute to diastolic dysfunction by recruiting cross-bridges, even at low Ca2+, and thereby increase myocardial stiffness. Key points Diastolic dysfunction in heart failure patients is evident from stiffening of the passive properties of the ventricular wall. Increased actomyosin

Older Subjects with β-cell Dysfunction have an Accentuated Incretin Release.

PubMed

Garduno-Garcia, José de Jesús; Gastaldelli, Amalia; DeFronzo, Ralph A; Lertwattanarak, Raweewan; Holst, Jens J; Musi, Nicolas

2018-04-16

Insulin secretion declines with age and this contributes to the increased risk of developing impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older subjects. Insulin secretion is regulated by the incretin hormones glucagon-like peptide (GLP) 1 and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses that incretin release is reduced in older subjects, and that this decline is associated with β-cell dysfunction. 40 young (25±3 y) and 53 older (74±7 y) lean non-diabetic subjects underwent a 2 h oral glucose tolerance test (OGTT). Based on the OGTT, subjects were divided in 3 groups: young normal glucose tolerant (Y-NGT, n=40), older with NGT (O-NGT, n=32), and older with IGT (O-IGT, n=21). Plasma insulin, C-peptide, GLP-1, and GIP concentrations were measured every 15-30 min. We quantitated insulin sensitivity (Matsuda index) and insulin secretory rate (ISR) by deconvolution of C-peptide with the calculation of β-cell glucose sensitivity. Matsuda index, early phase ISR (0-30min) and parameters of β-cell function were reduced in O-IGT vs. Y-NGT, but not in O-NGT. GLP-1 concentrations were elevated in both older groups [GLP-1_AUC0-120 was 2.8±0.1 in Y-NGT, 3.8±0.5 in O-NGT, and 3.7±0.4 nmol/l∙120 min in O-IGT (P<0.05)] while GIP secretion was elevated in O-NGT vs. Y-NGT [GIP_AUC0-120 was 4.7±0.3 in Y-NGT, 6.0±0.4 in O-NGT, and 4.8±0.3 nmol/l∙120 min in O-IGT (P<0.05)]. Aging is associated with an exaggerated GLP-1 secretory response. However, this was not sufficient to increase insulin first phase release in O-IGT and overcome insulin resistance.

Dysfunctional beliefs towards motherhood and postpartum depressive and anxiety symptoms: Uncovering the role of experiential avoidance.

PubMed

Fonseca, Ana; Monteiro, Fabiana; Canavarro, Maria Cristina

2018-06-06

This study aimed to examine the relationship between dysfunctional motherhood-related beliefs and postpartum anxiety and depression symptoms, and whether experiential avoidance may be a potential mechanism in explaining these relationships. A sample of 262 postpartum women participated in a cross-sectional online survey. The model presented a good fit (CFI = 0.96, RMSEA = 0.077) suggesting that more dysfunctional motherhood-related beliefs related with maternal responsibility and with others' judgments were associated with higher postpartum anxiety and depressive symptoms. Indirect effects through experiential avoidance were also found. Dysfunctional motherhood-related beliefs are cognitive vulnerabilities for postpartum psychological disorders and should be assessed to identify women that may be prone to early interventions. Moreover, dysfunctional beliefs seem to affect psychopathological symptoms by activating experiential avoidance strategies (e.g., rumination), which may accentuate the frequency of women's negative thoughts and emotions. Early interventions should target the promotion of acceptance of private negative experiences (psychological flexibility). © 2018 Wiley Periodicals, Inc.

Abnormal left ventricular longitudinal functional reserve in patients with diabetes mellitus: implication for detecting subclinical myocardial dysfunction using exercise tissue Doppler echocardiography

PubMed Central

Ha, Jong‐Won; Lee, Hyun‐Chul; Kang, Eun‐Seok; Ahn, Chul‐Min; Kim, Jin‐Mi; Ahn, Jeong‐Ah; Lee, Se‐Wha; Choi, Eui‐Young; Rim, Se‐Joong; Oh, Jae K; Chung, Namsik

2007-01-01

Background Sublinical myocardial dysfunction occurs in a significant number of patients with type 2 diabetes. Assessment of ventricular long‐axis function by measuring mitral annular velocities using tissue Doppler echocardiography (TDE) is thought to provide a more sensitive index of systolic and diastolic function. We hypothesised that augmentation of left ventricular (LV) longitudinal contraction and relaxation during exercise would be blunted in patients with type 2 diabetes. Methods Mitral annular systolic (S′) and early diastolic (E′) velocities were measured at rest and during supine bicycle exercise (25 W, 3 min increments) in 53 patients (27 male, mean age 53±14 years) with type 2 diabetes and 53 subjects with age and gender‐matched control. None had echocardiographic evidence of resting or inducible myocardial ischaemia. Results There were no significant differences in mitral inflow velocities at rest between the two groups. E′ and S′ at rest were also similar between the groups. However, S′ (7.1±1.3 vs 8.3±1.8 cm/s at 25 W, p = 0.0021; 8.1±1.5 vs 9.1±2.0 cm/s at 50 W, p = 0.026) and E′ (8.5±2.3 vs 9.9±3.1 cm/s at 25 W, p = 0.054; 9.1±2.1 vs 10.9±2.5 cm/s at 50 W, p = 0.0093) during exercise were significantly lower in patients with diabetes compared with controls. Longitudinal systolic and diastolic function reserve indices were significantly lower in patients with diabetes compared with that of controls (systolic index, 0.6±0.70 vs 1.2±1.5 cm/s at 25 W, p = 0.029; 1.2±1.2 vs 2.1±1.6 cm/s at 50 W, p = 0.009; diastolic index, 1.9±1.2 vs 2.5±2.2 cm/s at 25 W, p = 0.07; 2.3±1.3 vs 3.2±2.2 cm/s at 50 W, p = 0.031). Conclusion In conclusion, unlike resting mitral inflow and annular velocities, changes of systolic and diastolic velocities of the mitral annulus during exercise were significantly reduced in patients with type 2 diabetes compared with the

Accelerated and accentuated neurocognitive aging in HIV infection.

PubMed

Sheppard, David P; Iudicello, Jennifer E; Morgan, Erin E; Kamat, Rujvi; Clark, Lindsay R; Avci, Gunes; Bondi, Mark W; Woods, Steven Paul

2017-06-01

There is debate as to whether the neurocognitive changes associated with HIV infection represent an acceleration of the typical aging process or more simply reflect a greater accentuated risk for age-related declines. We aimed to determine whether accelerated neurocognitive aging is observable in a sample of older HIV-infected individuals compared to age-matched seronegatives and older old (i.e., aged ≥65) seronegative adults. Participants in a cross-sectional design included 48 HIV-seronegative (O-) and 40 HIV-positive (O+) participants between the ages of 50-65 (mean ages = 55 and 56, respectively) and 40 HIV-seronegative participants aged ≥65 (OO-; mean age = 74) who were comparable for other demographics. All participants were administered a brief neurocognitive battery of attention, episodic memory, speeded executive functions, and confrontation naming (i.e., Boston Naming Test). The O+ group performed more poorly than the O- group (i.e., accentuated aging), but not differently from the OO- on digit span and initial recall of a supraspan word list, consistent with an accelerating aging profile. However, the O+ group's performance was comparable to the O- group on all other neurocognitive tests (ps > 0.05). These data partially support a model of accelerated neurocognitive aging in HIV infection, which was observed in the domain of auditory verbal attention, but not in the areas of memory, language, or speeded executive functions. Future studies should examine whether HIV-infected adults over 65 evidence accelerated aging in downstream neurocognitive domains and subsequent everyday functioning outcomes.

Chinese patent medicine Xin-Ke-Shu inhibits Ca2+ overload and dysfunction of fatty acid β-oxidation in rats with myocardial infarction induced by LAD ligation.

PubMed

Yang, Yong; Jia, Hongmei; Yu, Meng; Zhou, Chao; Sun, Lili; Zhao, Yang; Zhang, Hongwu; Zou, Zhongmei

2018-03-15

Myocardial infarction (MI) occurs during a sustained insufficient blood supply to the heart, eventually leading to myocardial necrosis. Xin-Ke-Shu tablet (XKS) is a prescription herbal compound and a patented medicine extensively used in the clinical treatment of coronary heart disease (CHD). To understand the molecular mechanism of the XKS action against MI in detail, it is necessary to investigate the altered metabolome and related pathways coincident with clinical features. In this study, tissue-targeted metabonomics based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) were developed to explore the metabolic changes associated with XKS treatment in the heart tissue of rats with MI induced by a left anterior descending coronary artery ligation (LAD). The metabolic disorder induced by LAD was alleviated after low-dose XKS (LD) and intermediate-dose XKS (MD) treatment. XKS modulated six perturbed metabolic pathways. Among them, inhibition of Ca 2+ overload and dysfunction of fatty acid β-oxidation-related metabolic pathways likely underlie the therapeutic effects of XKS against MI. In agreement with its observed effect on metabolite perturbation, XKS reversed the over-expression of the four key proteins, long-chain acyl-CoA synthetase 1 (ACSL1), carnitine palmitoyl transferase-1 (CPT1B), calcium/calmodulin-dependent kinase II (CaMKII), and phospholipase A2IIA (PLA2IIA). Both metabolite and protein changes suggested that XKS exerts its therapeutic effect on metabolic perturbations in LAD-induced MI mainly by inhibiting the Ca 2+ overload and fatty acid β-oxidation dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessment of myocardial viability: comparison of echocardiography versus cardiac magnetic resonance imaging in the current era.

PubMed

Tomlinson, David R; Becher, Harald; Selvanayagam, Joseph B

2008-06-01

Detecting viable myocardium, whether hibernating or stunned, is of clinical significance in patients with coronary artery disease and left ventricular dysfunction. Echocardiographic assessments of myocardial thickening and endocardial excursion during dobutamine infusion provide a highly specific marker for myocardial viability, but with relatively less sensitivity. The additional modalities of myocardial contrast echocardiography and tissue Doppler have recently been proposed to provide further, quantitative measures of myocardial viability assessment. Cardiac magnetic resonance (CMR) has become popular for the assessment of myocardial viability as it can assess cardiac function, volumes, myocardial scar, and perfusion with high-spatial resolution. Both 'delayed enhancement' CMR and dobutamine stress CMR have important roles in the assessment of patients with ischaemic cardiomyopathy. This article reviews the recent advances in both echocardiography and CMR for the clinical assessment of myocardial viability. It attempts to provide a pragmatic approach toward the patient-specific assessment of this important clinical problem.

Predictive factor of secondary tricuspid regurgitation after aortic valve replacement for aortic stenosis: the importance of myocardial hypertrophy and diastolic dysfunction.

PubMed

Igarashi, Takashi; Tanji, Masahiro; Takahashi, Koki; Ishida, Keiichi; Sasaki, Satomi; Yokoyama, Hitoshi

2017-05-01

The aim of this study is to determine the predictors of secondary tricuspid regurgitation after aortic valve replacement for aortic stenosis. Seventy-one patients, who underwent aortic valve replacement for aortic stenosis at our institute from January 2006 to July 2011, were divided into two groups: an STR group, which included 15 patients with moderate or greater than moderate secondary tricuspid regurgitation at a follow-up visit and a control group. Echocardiography was performed before surgery, at discharge, and at a late follow-up visit (mean follow-up 36 ± 19 months, range 0-77). Preoperatively, the number of women (p < .01), body surface area (p < .001), and relative wall thickness (0.60 ± 0.15 vs 0.71 ± 0.13, p = .022) showed significant differences between the two groups. At a follow-up visit, moderate or severe mitral regurgitation (p = .0001) and severe diastolic dysfunction (p = .003) showed significant differences between the two groups. In the Cox regression analysis, moderate or severe mitral regurgitation at follow-up (p = .038, hazard ratio 4.394, 95% CI 1.085-17.791) was the only independent predictor of secondary tricuspid regurgitation. This study suggested that preoperative concentric myocardial hypertrophy and diastolic dysfunction were associated with development of the secondary tricuspid regurgitation at late follow-up.

Calcineurin Regulates Myocardial Function during Acute Endotoxemia

PubMed Central

Joshi, Mandar S.; Julian, Mark W.; Huff, Jennifer E.; Bauer, John A.; Xia, Yong; Crouser, Elliott D.

2006-01-01

Rationale: Cyclosporin A (CsA) is known to preserve cardiac contractile function during endotoxemia, but the mechanism is unclear. Increased nitric oxide (NO) production and altered mitochondrial function are implicated as mechanisms contributing to sepsis-induced cardiac dysfunction, and CsA has the capacity to reduce NO production and inhibit mitochondrial dysfunction relating to the mitochondrial permeability transition (MPT). Objectives: We hypothesized that CsA would protect against endotoxin-mediated cardiac contractile dysfunction by attenuating NO production and preserving mitochondrial function. Methods: Left ventricular function was measured continuously over 4 h in cats assigned as follows: control animals (n = 7); LPS alone (3 mg/kg, n = 8); and CsA (6 mg/kg, n = 7), a calcineurin inhibitor that blocks the MPT, or tacrolimus (FK506, 0.1 mg/kg, n = 7), a calcineurin inhibitor lacking MPT activity, followed in 30 min by LPS. Myocardial tissue was then analyzed for NO synthase-2 expression, tissue nitration, protein carbonylation, and mitochondrial morphology and function. Measurements and Main Results: LPS treatment resulted in impaired left ventricular contractility, altered mitochondrial morphology and function, and increased protein nitration. As hypothesized, CsA pretreatment normalized cardiac performance and mitochondrial respiration and reduced myocardial protein nitration. Unexpectedly, FK506 pretreatment had similar effects, normalizing both cardiac and mitochondrial parameters. However, CsA and FK506 pretreatments markedly increased protein carbonylation in the myocardium despite elevated manganese superoxide dismutase activity during endotoxemia. Conclusions: Our data indicate that calcineurin is a critical regulator of mitochondrial respiration, tissue nitration, protein carbonylation, and contractile function in the heart during acute endotoxemia. PMID:16424445

Myocardial dysfunction and norepinephrine release in the isolated rat heart injured by electrolysis-induced oxygen free radicals.

PubMed

Chahine, R; Chen, X; Yamaguchi, N; de Champlain, J; Nadeau, R

1991-03-01

In the present investigation, we used electrolysis as a source of oxygen free radicals to test their possible role in norepinephrine release, as well as in the mechanism of cellular injury, cardiac dysfunction and arrhythmias. In the isolated rat heart perfused under constant pressure, according to the Langendorff technique, electrolysis of the Krebs-Henseleit solution (10 mA d.c. current for 1 min) produced myocardial irreversible dysfunction within 5 min. Fifteen minutes after electrolysis, significant falls in the left ventricular pressure (from 87.5 +/- 6.8 to 33.7 +/- 5.2 mmHg), dP/dt max (from 1230 +/- 90 to 375 +/- 59 mmHg/s), heart rate (from 287 +/- 18 to 119 +/- 13.5 beats/min) and coronary flow (from 14.8 +/- 9 to 3.4 +/- 1.7 ml/min) were observed, along with an increase in left ventricular end diastolic pressure from 10 to 50 +/- 3.5 mmHg (n = 8, P less than 0.01). AV conduction block and/or sinus bradycardia were noted in all preparations. An increase in norepinephrine washout from 298.5 +/- 84 at baseline to 610 +/- 110 pg/min/g 5 min after electrolysis was measured (n = 8, P less than 0.05) and a 44.8 +/- 9.2% and 35 +/- 7.5% reduction, respectively in right and left ventricular tissue norepinephrine content was also found at 30 min (n = 5, P less than 0.05). Pretreatment of the hearts 10 min before electrolysis and throughout the experimental period by superoxide dismutase (SOD; 100 U/ml), catalase (150 U/ml), a combination of SOD + catalase or mannitol (50 mM) partially blocked the deleterious effect of free radicals and permitted a functional recovery of 50 to 60%, mannitol being the more potent protective agent. Furthermore, these scavengers also significantly reduced norepinephrine washout.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial Viability: From Proof of Concept to Clinical Practice

PubMed Central

Tan, Timothy C.; Hsu, Chijen; Denniss, Alan Robert

2016-01-01

Ischaemic left ventricular (LV) dysfunction can arise from myocardial stunning, hibernation, or necrosis. Imaging modalities have become front-line methods in the assessment of viable myocardial tissue, with the aim to stratify patients into optimal treatment pathways. Initial studies, although favorable, lacked sufficient power and sample size to provide conclusive outcomes of viability assessment. Recent trials, including the STICH and HEART studies, have failed to confer prognostic benefits of revascularisation therapy over standard medical management in ischaemic cardiomyopathy. In lieu of these recent findings, assessment of myocardial viability therefore should not be the sole factor for therapy choice. Optimization of medical therapy is paramount, and physicians should feel comfortable in deferring coronary revascularisation in patients with coronary artery disease with reduced LV systolic function. Newer trials are currently underway and will hopefully provide a more complete understanding of the pathos and management of ischaemic cardiomyopathy. PMID:27313943

Myocardial perfusion imaging study of CO(2)-induced panic attack.

PubMed

Soares-Filho, Gastão L F; Machado, Sergio; Arias-Carrión, Oscar; Santulli, Gaetano; Mesquita, Claudio T; Cosci, Fiammetta; Silva, Adriana C; Nardi, Antonio E

2014-01-15

Chest pain is often seen alongside with panic attacks. Moreover, panic disorder has been suggested as a risk factor for cardiovascular disease and even a trigger for acute coronary syndrome. Patients with coronary artery disease may have myocardial ischemia in response to mental stress, in which panic attack is a strong component, by an increase in coronary vasomotor tone or sympathetic hyperactivity setting off an increase in myocardial oxygen consumption. Indeed, coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. These findings correlating panic disorder with coronary artery disease lead us to raise questions about the favorable prognosis of chest pain in panic attack. To investigate whether myocardial ischemia is the genesis of chest pain in panic attacks, we developed a myocardial perfusion study through research by myocardial scintigraphy in patients with panic attacks induced in the laboratory by inhalation of 35% carbon dioxide. In conclusion, from the data obtained, some hypotheses are discussed from the viewpoint of endothelial dysfunction and microvascular disease present in mental stress response. Copyright © 2014 Elsevier Inc. All rights reserved.

Ablation of toll-like receptor 4 attenuates aging-induced myocardial remodeling and contractile dysfunction through NCoRI-HDAC1-mediated regulation of autophagy.

PubMed

Wang, Shuyi; Ge, Wei; Harns, Carrie; Meng, Xianzhong; Zhang, Yingmei; Ren, Jun

2018-04-13

Aging is usually accompanied with overt structural and functional changes as well as suppressed autophagy in the heart although the precise regulatory mechanisms are somewhat unknown. Here we evaluated the role of the innate proinflammatory mediator toll-like receptor 4 (TLR4) in cardiac aging and the underlying mechanism with a focus on autophagy. Cardiac geometry and function were monitored in young or old wild-type (WT) and TLR4 knockout (TLR4 -/- ) mice using echocardiography, IonOptix® edge-detection and fura-2 techniques. Levels of autophagy and mitophagy, nuclear receptor corepressor 1 (NCoR1) and histone deacetylase I (HDAC1) were examined using western blot. Transmission electronic microscopy (TEM) was employed to monitor myocardial ultrastructure. Our results revealed that TLR4 ablation alleviated advanced aging (24 months)-induced changes in myocardial remodeling (increased heart weight, chamber size, cardiomyocyte cross-sectional area), contractile function and intracellular Ca 2+ handling as well as autophagy and mitophagy [Beclin-1, Atg5, LC3B, PTEN-induced putative kinase 1 (PINK1), Parkin and p62]. Aging downregulated levels of NCoR1 and HDAC1 as well as their interaction, the effects were significantly attenuated or negated by TLR4 ablation. Advanced aging disturbed myocardial ultrastructure as evidenced by loss of myofilament alignment and swollen mitochondria, which was obliterated by TLR4 ablation. Moreover, aging suppressed autophagy (GFP-LC3B puncta) in neonatal mouse cardiomyocytes, the effect of which was negated by the TLR4 inhibitor CLI-095. Inhibition of HDCA1 using apicidin cancelled off CLI095-induced beneficial response of GFP-LC3B puncta against aging. Our data collectively indicate a role for TLR4-mediated autophagy in cardiac remodeling and contractile dysfunction in aging through a HDAC1-NCoR1-dependent mechanism. Copyright © 2018 Elsevier Ltd. All rights reserved.

The GSK-3 family as therapeutic target for myocardial diseases

PubMed Central

Lal, Hind; Ahmad, Firdos; Woodgett, James; Force, Thomas

2014-01-01

GSK-3 is one of the very few signaling molecules that regulate a truly astonishing number of critical intracellular signaling pathways. It has been implicated in a number of diseases including heart failure, bipolar disorder, diabetes, Alzheimer’s disease, aging, inflammation and cancer. Furthermore, a recent clinical trial has validated the feasibility of targeting GSK-3 with small molecule inhibitors for human diseases. In the current review we will focus on its expanding role in the heart, concentrating primarily on recent studies that have employed cardiomyocyte- and fibroblast-specific conditional gene deletion in mouse models. We will highlight the role of the GSK-3 isoforms in various pathological conditions including myocardial aging, ischemic injury, myocardial fibrosis and cardiomyocyte proliferation. We will discuss our recent findings that deletion of GSK-3α specifically in cardiomyocytes attenuates ventricular remodeling and cardiac dysfunction post-MI by limiting scar expansion and promoting cardiomyocyte proliferation. The recent emergence of GSK-3β as a regulator of myocardial fibrosis will also be discussed. We will review our very recent findings that specific deletion of GSK-3β in cardiac fibroblasts leads to fibrogenesis, left ventricular dysfunction and excessive scarring in the ischemic heart. Finally, we will examine the underlying mechanisms that drive the aberrant myocardial fibrosis in the models in which GSK-3β is specifically deleted in cardiac fibroblasts. We will summarize these recent results and offer explanations, whenever possible, and hypotheses when not. For these studies we will rely heavily on our models and those of others to reconcile some of the apparent inconsistencies in the literature. PMID:25552693

Cumulative Burden of Myocardial Dysfunction in Cardiac Amyloidosis Assessed Using Four-Chamber Cardiac Strain.

PubMed

Kado, Yuichiro; Obokata, Masaru; Nagata, Yasufumi; Ishizu, Tomoko; Addetia, Karima; Aonuma, Kazutaka; Kurabayashi, Masahiko; Lang, Roberto M; Takeuchi, Masaaki; Otsuji, Yutaka

2016-11-01

The aim of this study was to test the hypothesis that prognosis in patients with cardiac amyloidosis is closely coupled with amyloid burden in all four cardiac chambers. The goal was to evaluate longitudinal strain (LS) in each cardiac chamber and to determine whether LS in specific cardiac chambers is preferentially associated with prognosis over conventional two-dimensional echocardiographic parameters in patients with cardiac amyloidosis. Patients with two phenotypes of left ventricular (LV) hypertrophy (cardiac amyloidosis in 55 patients and nonobstructive hypertrophic cardiomyopathy in 40 patients) and 55 healthy subjects were retrospectively enrolled for the simultaneous assessment of LS of all four cardiac chambers in the apical four-chamber view. Patients with cardiac amyloidosis were followed up to record major adverse cardiovascular events, including cardiac death, heart transplantation, nonfatal myocardial infarction, ventricular tachyarrhythmia, and exacerbation of heart failure requiring hospitalization. LS in each chamber was significantly depressed in patients with both LV hypertrophy phenotypes compared with healthy subjects. Right atrial LS was significantly lower in patients with cardiac amyloidosis than those with nonobstructive hypertrophic cardiomyopathy after adjusting for LV ejection fraction and LV mass index. During a median follow-up period of 10 months, major adverse cardiovascular events developed in 22 patients with cardiac amyloidosis. Four-chamber LS were significantly associated with major adverse cardiovascular events, with incremental value over traditional echocardiographic parameters. Cardiac amyloidosis involves all cardiac chambers, and thus, chamber-specific strain analysis may be useful to assess the total cumulative burden of cardiac dysfunction. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

How and When Accentuation Influences Temporally Selective Attention and Subsequent Semantic Processing during On-Line Spoken Language Comprehension: An ERP Study

ERIC Educational Resources Information Center

Li, Xiao-qing; Ren, Gui-qin

2012-01-01

An event-related brain potentials (ERP) experiment was carried out to investigate how and when accentuation influences temporally selective attention and subsequent semantic processing during on-line spoken language comprehension, and how the effect of accentuation on attention allocation and semantic processing changed with the degree of…

Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction).

PubMed

Sanz-Ruiz, Ricardo; Casado Plasencia, Ana; Borlado, Luis R; Fernández-Santos, María Eugenia; Al-Daccak, Reem; Claus, Piet; Palacios, Itziar; Sádaba, Rafael; Charron, Dominique; Bogaert, Jan; Mulet, Miguel; Yotti, Raquel; Gilaberte, Immaculada; Bernad, Antonio; Bermejo, Javier; Janssens, Stefan; Fernández-Avilés, Franciso

2017-06-23

Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results. In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior. With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure. This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarction patients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398. © 2017 American Heart Association, Inc.

Myocardial oedema in acute myocarditis detected by echocardiographic 2D myocardial deformation analysis.

PubMed

Løgstrup, B B; Nielsen, J M; Kim, W Y; Poulsen, S H

2016-09-01

strain correlated significantly with the amount of oedema (r = 0.65; P < 0.001). We found that both the epicardial longitudinal and the endocardial longitudinal systolic strains were significantly correlated with oedema (r = 0.55; P = 0.003 and r = 0.54; P < 0.001). In patients with acute myocarditis, 2D speckle-tracking echocardiography was a useful tool in the diagnostic process of acute myocarditis. Global longitudinal strain adds important information that can support clinical and conventional echocardiographic evaluation, especially in patients with preserved LV ejection fraction in relation to the diagnosis and degree of myocardial dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

The amelioration of cardiac dysfunction after myocardial infarction by the injection of keratin biomaterials derived from human hair.

PubMed

Shen, Deliang; Wang, Xiaofang; Zhang, Li; Zhao, Xiaoyan; Li, Jingyi; Cheng, Ke; Zhang, Jinying

2011-12-01

Cardiac dysfunction following acute myocardial infarction is a major cause of advanced cardiomyopathy. Conventional pharmacological therapies rely on prompt reperfusion and prevention of repetitive maladaptive pathways. Keratin biomaterials can be manufactured in an autologous fashion and are effective in various models of tissue regeneration. However, its potential application in cardiac regeneration has not been tested. Keratin biomaterials were derived from human hair and its structure morphology, carryover of beneficial factors, biocompatibility with cardiomyocytes, and in vivo degradation profile were characterized. After delivery into infarcted rat hearts, the keratin scaffolds were efficiently infiltrated by cardiomyocytes and endothelial cells. Injection of keratin biomaterials promotes angiogenesis but does not exacerbate inflammation in the post-MI hearts. Compared to control-injected animals, keratin biomaterials-injected animals exhibited preservation of cardiac function and attenuation of adverse ventricular remodeling over the 8 week following time course. Tissue western blot analysis revealed up-regulation of beneficial factors (BMP4, NGF, TGF-beta) in the keratin-injected hearts. The salient functional benefits, the simplicity of manufacturing and the potentially autologous nature of this biomaterial provide impetus for further translation to the clinic. Copyright © 2011 Elsevier Ltd. All rights reserved.

Association of Exercise Training with Tobacco Smoking Prevents Fibrosis but has Adverse Impact on Myocardial Mechanics.

PubMed

Reis Junior, Dermeval; Antonio, Ednei Luiz; de Franco, Marcello Fabiano; de Oliveira, Helenita Antonia; Tucci, Paulo José Ferreira; Serra, Andrey Jorge

2016-12-01

There was no data for cardiac repercussion of exercise training associated with tobacco smoking. This issue is interesting because some smoking people can be enrolled in an exercise-training program. Thus, we evaluated swimming training effects on the function and structural myocardial in rats exposed to tobacco smoking. Male Wistar rats were assigned to one of four groups: C, untrained rats without exposure to tobacco smoking; E, exercised rats without exposure to tobacco smoking; CS, untrained rats exposed to tobacco smoking; ECS, exercised rats exposed to tobacco smoking. Rats swam five times a week twice daily (60min per session) for 8 weeks. Before each bout exercise, rats breathed smoke from 20 cigarettes for 60min. Twenty-four hours after the last day of the protocol, papillary muscles were isolated for in vitro analysis of myocardial mechanics. The myocardial mass and nuclear cardiomyocyte volume were used as hypertrophy markers, and collagen content was determined by picrosirius red staining. There was a well-pronounced myocardial hypertrophic effect for two interventions. The exercise blunted myocardial collagen increases induced by tobacco smoking. However, exercise and tobacco-smoking association was deleterious to myocardial performance. Thereby, in vitro experiments with papillary muscles contracting in isometric showed impairment myocardial inotropism in exercised rats exposed to tobacco smoking. This work presents novel findings on the role of exercise training on cardiac remodeling induced by tobacco smoking. Although exercise has mitigated tissue fibrosis, their association with tobacco smoking exacerbated hypertrophy and in vitro myocardial dysfunction. This is first study to show that the association of an aerobic exercise training with tobacco smoking intensifies the phenotype of pathological cardiac hypertrophy. Therefore, the combination of interventions resulted in exacerbated myocardial hypertrophy and contractility dysfunction. These

Regional myocardial extraction of a radioiodinated branched chain fatty acid during right ventricular pressure overload due to acute pulmonary hypertension

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

Hurford, W.; Lowenstein, E.; Zapol, W.

1985-05-01

To determine whether branched chain fatty acid extraction is reduced during right ventricular (RV) dysfunction due to acute pulmonary artery hypertension, studies were done in 6 anesthetized dogs. Regional branched chain fatty acid extraction was measured by comparing the myocardial uptake of I-125 labeled 15-(p-(iodophenyl))-3-methylpentadecanoic acid (I-PDA) to myocardial blood flow. Acute pulmonary hypertension was induced by incremental intravenous injection of 100 micron diameter glass beads into six pentobarbital anesthetized, mechanically ventilated dogs. Myocardial blood flow was measured by radiolabeled microspheres both under baseline conditions and during pulmonary hypertension. Mean RV pressure rose from 12 +- 2 (mean +- SEM)more » to 30 +-3mmHg resulting in a 225 +- 16% increase in RV stroke work. RV ejection fraction, as assessed by gated blood pool scans fell from 39 +- 2 to 18 +- 2%. Left ventricular (LV) pressures, stroke work and ejection fraction were unchanged. Myocardial blood flow increased 132 + 59% in the RV free wall and 67 +- 22% in the RV septum. LV blood flow was unchanged. Despite increased RV work and myocardial blood flow, no differences were noted in the branched chain fatty acid extraction ratios among LV or RV free walls or septum. The authors conclude that early RV dysfunction associated with pulmonary artery hypertension is not due to inadequate myocardial blood flow or branched chain fatty acid extraction.« less

Levosimendan reduces myocardial damage and improves cardiodynamics in streptozotocin induced diabetic cardiomyopathy via SERCA2a/NCX1 pathway.

PubMed

Akhtar, Md Sayeed; Pillai, Krishna Kolappa; Hassan, Md Quamrul; Dhyani, Neha; Ismail, Md Vasim; Najmi, Abul Kalam

2016-05-15

Diabetic cardiomyopathy (DCM) is one of the most common causes of mortality. Its pathophysiology is not fully understood and involve number of factors including, cardiovascular and metabolic disorders. The present study was designed to study the pathogenesis of DCM and to explore the effects of levosimendan along with either ramipril or insulin in the long term management of DCM. Streptozotocin (STZ) was used to develop DCM in Wistar rats at the dose of 25mg/kg body weight for three consecutive days. Rats were randomly divided into 9 groups and treatments were started after 2weeks of STZ administration. Persistent hyperglycemia was observed in STZ treated rats, leading to significant contractile dysfunction as evidenced by decreased left ventricular pressure (LVP), +LV (dp/dt), -LV (dp/dt) as well as elevated Tau and LVEDP. Marked myocardial damage such as fibrosis, increased wall tension, depletion of contractile proteins were observed as evidenced by increased levels of TGF-β, BNP, cTroponin-I, as well as decreased expression of SERCA2a and NCX1 proteins in diabetic rats. The levosimendan alone and also in combination with either ramipril or insulin significantly normalized the myocardial dysfunctions developed during the course of persistent hyperglycemia. The study suggests that levosimendan treatment improves cardiac dysfunction significantly. Its combined use with ramipril proves better than with insulin in correcting myocardial performance as well as reduction in myocardial damage. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model.

PubMed

Axelsson, Birger; Häggmark, Sören; Svenmarker, Staffan; Johansson, Göran; Gupta, Anil; Tydén, Hans; Wouters, Patrick; Haney, Michael

2016-09-01

It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. A global ischemic injury was induced by repetitive left main stem coronary artery occlusions. Load-independent indices of LV function were assessed before and after ventricular injury, after milrinone treatment, and finally after addition of levosimendan to the milrinone treatment. Nonparametric, within-group comparisons were made. The protocol was completed in 12 pigs, 7 of which received the inotrope treatment and 5 of which served as controls. Milrinone led to positive lusitropic effects seen by improvement in tau after myocardial stunning. The addition of levosimendan to milrinone further increased lusitropic state. The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context. © The Author(s) 2016.

Is 2D speckle tracking echocardiography useful for detecting and monitoring myocardial dysfunction in adult m.3243A>G carriers? - a retrospective pilot study.

PubMed

Koene, S; Timmermans, J; Weijers, G; de Laat, P; de Korte, C L; Smeitink, J A M; Janssen, M C H; Kapusta, L

2017-03-01

Cardiomyopathy is a common complication of mitochondrial disorders, associated with increased mortality. Two dimensional speckle tracking echocardiography (2DSTE) can be used to quantify myocardial deformation. Here, we aimed to determine the usefulness of 2DSTE in detecting and monitoring subtle changes in myocardial dysfunction in carriers of the 3243A>G mutation in mitochondrial DNA. In this retrospective pilot study, 30 symptomatic and asymptomatic carriers of the mitochondrial 3243A>G mutation of whom two subsequent echocardiograms were available were included. We measured longitudinal, circumferential and radial strain using 2DSTE. Results were compared to published reference values. Speckle tracking was feasible in 90 % of the patients for longitudinal strain. Circumferential and radial strain showed low face validity (low number of images with sufficient quality; suboptimal tracking) and were therefore rejected for further analysis. Global longitudinal strain showed good face validity, and was abnormal in 56-70 % (depending on reference values used) of the carriers (n = 27). Reproducibility was good (mean difference of 0.83 for inter- and 0.40 for intra-rater reproducibility; ICC 0.78 and 0.89, respectively). The difference between the first and the second measurement exceeded the measurement variance in 39 % of the cases (n = 23; feasibility of follow-up 77 %). Even in data collected as part of clinical care, two-dimensional strain echocardiography seems a feasible method to detect and monitor subtle changes in longitudinal myocardial deformation in adult carriers of the mitochondrial 3243A>G mutation. Based on our data and the reported accuracy of global longitudinal strain in other studies, we suggest the use of global longitudinal strain in a prospective follow-up or intervention study.

Mitochondrial Bioenergetics and Dysfunction in Failing Heart.

PubMed

Sheeran, Freya L; Pepe, Salvatore

2017-01-01

Energy insufficiency has been recognized as a key feature of systolic heart failure. Although mitochondria have long been known to sustain myocardial work energy supply, the capacity to therapeutically target mitochondrial bioenergetics dysfunction is hampered by a complex interplay of multiple perturbations that progressively compound causing myocardial failure and collapse. Compared to non-failing human donor hearts, activity rates of complexes I and IV, nicotinamide nucleotide transhydrogenase (NADPH-transhydrogenase, Nnt) and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase and aconitase are markedly decreased in end-stage heart failure. Diminished REDOX capacity with lower total glutathione and coenzyme Q 10 levels are also a feature of chronic left ventricular failure. Decreased enzyme activities in part relate to abundant and highly specific oxidative, nitrosylative, and hyperacetylation modifications. In this brief review we highlight that energy deficiency in end-stage failing human left ventricle predominantly involves concomitantly impaired activities of key electron transport chain and Krebs cycle enzymes rather than altered expression of respective genes or proteins. Augmented oxidative modification of these enzyme subunit structures, and the formation of highly reactive secondary metabolites, implicates dysfunction due to diminished capacity for management of mitochondrial reactive oxygen species, which contribute further to progressive decreases in bioenergetic capacity and contractile function in human heart failure.

Myocardial scintigraphy with 201thallium in pediatric cardiology: A review of 52 cases

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

Bjoerkhem, G.E.; Evander, E.; White, T.

1990-01-01

We report our experience of myocardial scintigraphy with 201thallium (201Tl) in 52 children, aged 4 days to 18 years, in which 80 studies were made primarily to demonstrate or exclude impaired myocardial perfusion. For analysis, the patients were divided into the following eight groups: group I, coronary artery malformations (five patients); group II, Kawasaki's syndrome (six patients); group III, arterial switch operation (seven patients); group IV, dilated cardiomyopathy (18 patients); group V, hypertrophic cardiomyopathy (four patients); group VI, myocardial dysfunction after surgery for congenital heart disease (five patients); group VII, pulmonary atresia (three patients); and group VIII, miscellaneous (four patients).more » Myocardial scintigraphy was performed with a planar or tomographic technique at rest or after exercise (four patients). Isotope-uptake defects, indicating impaired myocardial perfusion, were present in 14 patients, including small infants. Defects were seen in all groups except those with hypertrophic cardiomyopathy and pulmonary atresia. The absence of such defects in several of the patients with Kawasaki's syndrome was particularly valuable as it made coronary angiography unnecessary. In the other groups of patients myocardial scintigraphy was a valuable adjunct to other investigations.« less

Myocardial viability assessment with dynamic low-dose iodine-123-iodophenylpentadecanoic acid metabolic imaging: comparison with myocardial biopsy and reinjection SPECT thallium after myocardial infarction.

PubMed

Murray, G L; Schad, N C; Magill, H L; Vander Zwaag, R

1994-04-01

Aggressive cardiac revascularization requires recognition of stunned and hibernating myocardium, and cost considerations may well govern the technique used. Dynamic low-dose (1 mCi) [123I]iodophenylpentadecanoic acid (IPPA) metabolic imaging is a potential alternative to PET using either 18FDG or 15O-water. Resting IPPA images were obtained from patients with severe ischemic cardiomyopathy, and transmural myocardial biopsies were obtained during coronary bypass surgery to confirm viability. Thirty-nine of 43 (91%) biopsies confirmed the results of the IPPA images with a sensitivity for viability of 33/36 (92%) and a specificity of 6/7 (86%). Postoperatively, wall motion improved in 80% of IPPA-viable, dysfunctional segments. Furthermore, when compared to reinjection thallium (SPECT-TI) scans after myocardial infarction, IPPA-SPECT-TI concordance occurred in 27/35 (77%) (K = 0.536, p = 0.0003). Similar to PET, IPPA demonstrated more viability than SPECT-TI, 26/35 (74%) versus 18/35 (51%) (p = 0.047). Metabolic IPPA cardiac viability imaging is a safe, inexpensive technique that may be a useful alternative to PET.

Hypothyroidism-induced myocardial damage and heart failure: an overlooked entity.

PubMed

Shuvy, Mony; Shifman, Oshrat E Tayer; Nusair, Samir; Pappo, Orit; Lotan, Chaim

2009-01-01

Hypothyroid state may induce cardiac muscle impairment such as diastolic dysfunction and abnormal relaxation time. Advanced heart failure in hypothyroid patients has been described only in severe symptomatic cases, mostly during myxedematous coma. We describe an unusual case of asymptomatic patient with hypothyroidism who presented with severely reduced cardiac function with elevated cardiac enzymes reflecting significant myocardial injury. Comprehensive evaluation for heart failure was suggestive only for long-standing untreated hypothyroidism. Endomyocadial biopsy demonstrated unique histological findings of mucopolysaccharide accumulation attributed to hypothyroid state. Asymptomatic hypothyroidism may cause severe reduction in cardiac function accompanied with elevated cardiac enzymes. To our knowledge, this is the first description of human myocardial biopsy revealing mucopolysaccharide accumulation attributed to hypothyroid state.

Simultaneous assessment of myocardial perfusion and function during mental stress in patients with chronic coronary artery disease.

PubMed

Arrighi, James A; Burg, Matthew; Cohen, Ira S; Soufer, Robert

2003-01-01

Mental stress (MS) is an important provocateur of myocardial ischemia in many patients with chronic coronary artery disease. The majority of laboratory assessments of ischemia in response to MS have included measurements of either myocardial perfusion or function alone. We performed this study to determine the relationship between alterations in perfusion and ventricular function during MS. Methods and results Twenty-eight patients with reversible perfusion defects on exercise or pharmacologic stress myocardial perfusion imaging (MPI) underwent simultaneous technetium 99m sestamibi single photon emission computed tomography (SPECT) MPI and transthoracic echocardiography at rest and during MS according to a mental arithmetic protocol. In all cases the MS study was performed within 4 weeks of the initial exercise or pharmacologic MPI that demonstrated ischemia. SPECT studies were analyzed visually with the use of a 13-segment model and quantitatively by semiautomated circumferential profile analysis. Echocardiograms were graded on a segmental model for regional wall motion on a 4-point scale. Of 28 patients, 18 (64%) had perfusion defects and/or left ventricular dysfunction develop during MS: 9 (32%) had myocardial perfusion defects develop, 6 (21%) had regional or global left ventricular dysfunction develop, and 3 (11%) had both perfusion defects and left ventricular dysfunction develop. The overall concordance between perfusion and function criteria for ischemia during MS was only 46%. Among 9 patients with MS-induced left ventricular dysfunction, 5 had new regional wall motion abnormalities and 4 had a global decrement in function. In patients with MS-induced ischemia by SPECT, the number of reversible perfusion defects was similar during both MS and exercise/pharmacologic stress (2.8 +/- 2.0 vs 3.5 +/- 1.8, P =.41). Hemodynamic changes during MS were similar whether patients were divided on the basis of perfusion defects or left ventricular dysfunction during MS

NDUFA4L2 protects against ischaemia/reperfusion-induced cardiomyocyte apoptosis and mitochondrial dysfunction by inhibiting complex I.

PubMed

Li, Jianhua; Bai, Caiyan; Guo, Junxia; Liang, Wanqian; Long, Jingning

2017-07-01

Myocardial ischaemia/reperfusion (I/R) injury may cause the apoptosis of cardiomyocytes as well as mitochondrial dysfunction. The aims of the present study were to investigate whether NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) on myocardial ischaemia-reperfusion (I/R) injury and the underlying molecular mechanism. The hypoxia-reperfusion (H/R) model was established in vitro using H9c2 cells to simulate I/R injury. NDUFA4L2 and complex I expression levels were detected using RT-PCR and western blot. The apoptosis of H9c2 cells was evaluated by flow cytometry and the expression of Bax and Bcl-2 was detected by western blot. The mitochondrial function was assessed by ATP concentration, mPTP opening and cytochrome c (cyto C) expression. Our data indicated that NDUFA4L2 expression was significantly down-regulated in myocardial H/R injury. Overexpression of NDUFA4L2 led to a dramatic prevention of H/R-induced apoptosis accompanied by a decrease in the expression of Bax and an increase in the expression of Bcl-2. Meanwhile, augmentation of NDUFA4L2 dramatically prevented mitochondrial dysfunction caused by H/R as reflecting in the increased ATP concentration, delayed mPTP opening, as well as down-regulated cyto C expression. Moreover, complex I activation was heightened and negatively regulated by NDUFA4L2. Silencing complex I conspicuously attenuated cell apoptosis and mitochondrial dysfunction. Taken together, our findings demonstrated that NDUFA4L2 protects against H/R injury by preventing myocardium apoptosis and mitochondrial dysfunction via the complex I, and may be a potential therapeutic approach for attenuating myocardial I/R injury. © 2017 John Wiley & Sons Australia, Ltd.

Right Ventricular Dysfunction in Chronic Lung Disease

PubMed Central

Kolb, Todd M.; Hassoun, Paul M.

2012-01-01

Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, except during acute exacerbations of chronic lung disease or when multiple co-morbidities are present. Treatment is targeted at correcting hypoxia and improving pulmonary gas exchange and mechanics. There are presently no convincing data to support the use of pulmonary hypertension-specific therapies in patients with right ventricular dysfunction secondary to chronic lung disease. PMID:22548815

Cardiac-Specific Deletion of Pyruvate Dehydrogenase Impairs Glucose Oxidation Rates and Induces Diastolic Dysfunction.

PubMed

Gopal, Keshav; Almutairi, Malak; Al Batran, Rami; Eaton, Farah; Gandhi, Manoj; Ussher, John Reyes

2018-01-01

Obesity and type 2 diabetes (T2D) increase the risk for cardiomyopathy, which is the presence of ventricular dysfunction in the absence of underlying coronary artery disease and/or hypertension. As myocardial energy metabolism is altered during obesity/T2D (increased fatty acid oxidation and decreased glucose oxidation), we hypothesized that restricting myocardial glucose oxidation in lean mice devoid of the perturbed metabolic milieu observed in obesity/T2D would produce a cardiomyopathy phenotype, characterized via diastolic dysfunction. We tested our hypothesis via producing mice with a cardiac-specific gene knockout for pyruvate dehydrogenase (PDH, gene name Pdha1 ), the rate-limiting enzyme for glucose oxidation. Cardiac-specific Pdha1 deficient ( Pdha1 Cardiac-/- ) mice were generated via crossing a tamoxifen-inducible Cre expressing mouse under the control of the alpha-myosin heavy chain (αMHC-MerCreMer) promoter with a floxed Pdha1 mouse. Energy metabolism and cardiac function were assessed via isolated working heart perfusions and ultrasound echocardiography, respectively. Tamoxifen administration produced an ~85% reduction in PDH protein expression in Pdha1 Cardiac-/- mice versus their control littermates, which resulted in a marked reduction in myocardial glucose oxidation and a corresponding increase in palmitate oxidation. This myocardial metabolism profile did not impair systolic function in Pdha1 Cardiac-/- mice, which had comparable left ventricular ejection fractions and fractional shortenings as their αMHC-MerCreMer control littermates, but did produce diastolic dysfunction as seen via the reduced mitral E/A ratio. Therefore, it does appear that forced restriction of glucose oxidation in the hearts of Pdha1 Cardiac-/- mice is sufficient to produce a cardiomyopathy-like phenotype, independent of the perturbed metabolic milieu observed in obesity and/or T2D.

TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy

PubMed Central

Shimauchi, Tsukasa; Numaga-Tomita, Takuro; Ito, Tomoya; Nishimura, Akiyuki; Matsukane, Ryosuke; Oda, Sayaka; Hoka, Sumio; Ide, Tomomi; Koitabashi, Norimichi; Uchida, Koji; Sumimoto, Hideki; Mori, Yasuo

2017-01-01

Myocardial atrophy is a wasting of cardiac muscle due to hemodynamic unloading. Doxorubicin is a highly effective anticancer agent but also induces myocardial atrophy through a largely unknown mechanism. Here, we demonstrate that inhibiting transient receptor potential canonical 3 (TRPC3) channels abolishes doxorubicin-induced myocardial atrophy in mice. Doxorubicin increased production of ROS in rodent cardiomyocytes through hypoxic stress–mediated upregulation of NADPH oxidase 2 (Nox2), which formed a stable complex with TRPC3. Cardiomyocyte-specific expression of TRPC3 C-terminal minipeptide inhibited TRPC3-Nox2 coupling and suppressed doxorubicin-induced reduction of myocardial cell size and left ventricular (LV) dysfunction, along with its upregulation of Nox2 and oxidative stress, without reducing hypoxic stress. Voluntary exercise, an effective treatment to prevent doxorubicin-induced cardiotoxicity, also downregulated the TRPC3-Nox2 complex and promoted volume load–induced LV compliance, as demonstrated in TRPC3-deficient hearts. These results illustrate the impact of TRPC3 on LV compliance and flexibility and, focusing on the TRPC3-Nox2 complex, provide a strategy for prevention of doxorubicin-induced cardiomyopathy. PMID:28768915

Energy Drinks and Myocardial Ischemia: A Review of Case Reports.

PubMed

Lippi, Giuseppe; Cervellin, Gianfranco; Sanchis-Gomar, Fabian

2016-07-01

The use and abuse of energy drinks (EDs) is constantly increasing worldwide. We performed a systematic search in Medline, Scopus and Web of Science to identify evidence about the potential link between these beverages and myocardial ischemia. Overall, 8 case reports could be detected, all of which described a realistic association between large intake of EDs and episodes of myocardial ischemia. Interestingly, no additional triggers of myocardial ischemia other than energy drinks could be identified in the vast majority of cases. Some plausible explanations can be brought in support of this association. Most of the biological effects of EDs are seemingly mediated by a positive inotropic effect on cardiac function, which entails increase in heart rate, cardiac output and contractility, stroke volume and arterial blood pressure. Additional biological abnormalities reported after EDs intake include increased platelet aggregation, endothelial dysfunction, hyperglycemia as well as an increase in total cholesterol, triglycerides and low-density lipoprotein cholesterol. Although a causal relationship between large consumption of EDs and myocardial ischemia cannot be definitely established so far, concerns about the cardiovascular risk of excessive consumption of these beverages are seemingly justified.

Oxidative stress and myocardial dysfunction in young rabbits after short term anabolic steroids administration.

PubMed

Germanakis, Ioannis; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tsitsimpikou, Christina; Goutzourelas, Nikolaos; Champsas, Maria Christakis; Stagos, Demetrios; Rentoukas, Elias; Tsatsakis, Aristidis M

2013-11-01

The present study focuses on the short term effects of repeated low level administration of turinabol and methanabol on cardiac function in young rabbits (4 months-old). The experimental scheme consisted of two oral administration periods, lasting 1 month each, interrupted by 1-month wash-out period. Serial echocardiographic evaluation at the end of all three experimental periods was performed in all animals. Oxidative stress markers have also been monitored at the end of each administration period. Treated animals originally showed significantly increased myocardial mass and systolic cardiac output, which normalized at the end of the wash out period. Re-administration led to increased cardiac output, at the cost though of a progressive myocardial mass reduction. A dose-dependent trend towards impaired longitudinal systolic, diastolic and global myocardial function was also observed. The adverse effects were more pronounced in the methanabol group. For both anabolic steroids studied, the low dose had no significant effects on oxidative stress markers monitored, while the high dose created a hostile oxidative environment. In conclusion, anabolic administration has been found to create a possible deleterious long term effect on the growth of the immature heart and should be strongly discouraged especially in young human subjects. Copyright © 2013 Elsevier Ltd. All rights reserved.

The accent method of voice therapy: effect of accentuations on FO, SPL, and airflow.

PubMed

Kotby, M N; Shiromoto, O; Hirano, M

1993-12-01

The effect of the increased flow rate (delta U) in response to the Accent Method exercises on fundamental frequency (FO) and sound pressure level (SPL) was studied in three subjects (professionally trained, trained, and untrained in this method). In all the subjects, the rhythmic accentuated exercises produced a variable degree of increase in FO (delta FO) and SPL (delta SPL). The professionally trained subject showed greater delta FO and delta SPL in response to the delta U in the fastest tempo, which requires higher skills. Both trained subjects showed a greater correlation between delta U and both delta SPL and delta FO, as well as between delta FO and delta SPL, as compared to the untrained subject. The effects of the accentuated exercises on FO and SPL in response to the increased airflow rate (delta U) thus appear to demonstrate the treating effectiveness of the Accent Method.

Myocardial Oxidative Stress in Infants Undergoing Cardiac Surgery.

PubMed

Sznycer-Taub, Nathaniel; Mackie, Stewart; Peng, Yun-Wen; Donohue, Janet; Yu, Sunkyung; Aiyagari, Ranjit; Charpie, John

2016-04-01

Cardiac surgery for congenital heart disease often necessitates a period of myocardial ischemia during cardiopulmonary bypass and cardioplegic arrest, followed by reperfusion after aortic cross-clamp removal. In experimental models, myocardial ischemia-reperfusion is associated with significant oxidative stress and ventricular dysfunction. A prospective observational study was conducted in infants (<1 year) who underwent elective surgical repair of a ventricular septal defect (VSD) or tetralogy of Fallot (TOF). Blood samples were drawn following anesthetic induction (baseline) and directly from the coronary sinus at 1, 3, 5, and 10 min following aortic cross-clamp removal. Samples were analyzed for oxidant stress using assays for thiobarbituric acid-reactive substances, protein carbonyl, 8-isoprostane, and total antioxidant capacity. For each subject, raw assay data were normalized to individual baseline samples and expressed as fold-change from baseline. Results were compared using a one-sample t test with Bonferroni correction for multiple comparisons. Sixteen patients (ten with TOF and six with VSD) were enrolled in the study, and there were no major postoperative complications observed. For the entire cohort, there was an immediate, rapid increase in myocardial oxidative stress that was sustained for 10 min following aortic cross-clamp removal in all biomarker assays (all P < 0.01), except total antioxidant capacity. Infant cardiac surgery is associated with a rapid, robust, and time-dependent increase in myocardial oxidant stress as measured from the coronary sinus in vivo. Future studies with larger enrollment are necessary to assess any association between myocardial oxidative stress and early postoperative outcomes.

Ultrastructural and cellular basis for the development of abnormal myocardial mechanics during the transition from hypertension to heart failure.

PubMed

Shah, Sanjiv J; Aistrup, Gary L; Gupta, Deepak K; O'Toole, Matthew J; Nahhas, Amanda F; Schuster, Daniel; Chirayil, Nimi; Bassi, Nikhil; Ramakrishna, Satvik; Beussink, Lauren; Misener, Sol; Kane, Bonnie; Wang, David; Randolph, Blake; Ito, Aiko; Wu, Megan; Akintilo, Lisa; Mongkolrattanothai, Thitipong; Reddy, Mahendra; Kumar, Manvinder; Arora, Rishi; Ng, Jason; Wasserstrom, J Andrew

2014-01-01

Although the development of abnormal myocardial mechanics represents a key step during the transition from hypertension to overt heart failure (HF), the underlying ultrastructural and cellular basis of abnormal myocardial mechanics remains unclear. We therefore investigated how changes in transverse (T)-tubule organization and the resulting altered intracellular Ca(2+) cycling in large cell populations underlie the development of abnormal myocardial mechanics in a model of chronic hypertension. Hearts from spontaneously hypertensive rats (SHRs; n = 72) were studied at different ages and stages of hypertensive heart disease and early HF and were compared with age-matched control (Wistar-Kyoto) rats (n = 34). Echocardiography, including tissue Doppler and speckle-tracking analysis, was performed just before euthanization, after which T-tubule organization and Ca(2+) transients were studied using confocal microscopy. In SHRs, abnormalities in myocardial mechanics occurred early in response to hypertension, before the development of overt systolic dysfunction and HF. Reduced longitudinal, circumferential, and radial strain as well as reduced tissue Doppler early diastolic tissue velocities occurred in concert with T-tubule disorganization and impaired Ca(2+) cycling, all of which preceded the development of cardiac fibrosis. The time to peak of intracellular Ca(2+) transients was slowed due to T-tubule disruption, providing a link between declining cell ultrastructure and abnormal myocardial mechanics. In conclusion, subclinical abnormalities in myocardial mechanics occur early in response to hypertension and coincide with the development of T-tubule disorganization and impaired intracellular Ca(2+) cycling. These changes occur before the development of significant cardiac fibrosis and precede the development of overt cardiac dysfunction and HF.

Common presentation of rare diseases: Left ventricular hypertrophy and diastolic dysfunction.

PubMed

Linhart, Ales; Cecchi, Franco

2018-04-15

Left ventricular hypertrophy may be a consequence of a hemodynamic overload or a manifestation of several diseases affecting different structural and functional proteins of cardiomyocytes. Among these, sarcomeric hypertrophic cardiomyopathy (HCM) represents the most frequent cause. In addition, several metabolic diseases lead to myocardial thickening, either due to intracellular storage (glycogen storage and lysosomal diseases), extracellular deposition (TTR and AL amyloidosis) or due to abnormal energy metabolism (mitochondrial diseases). The recognition of these rare causes of myocardial hypertrophy is important for family screening strategies, risk assessment, and treatment. Moreover, as there are specific therapies for some forms of HCM including enzyme substitution and chaperone therapies and specific treatments for TTR amyloidosis, a differential diagnosis should be sought in all patients with unexplained left ventricular hypertrophy. Diastolic dysfunction is a key feature of HCM and its phenocopies. Its assessment is complex and requires evaluation of several functional parameters and structural changes. Severe diastolic dysfunction carries a negative prognostic implication and its value in differential diagnosis is limited. Copyright © 2018 Elsevier B.V. All rights reserved.

Parametric techniques for characterizing myocardial tissue by magnetic resonance imaging (part 1): T1 mapping.

PubMed

Perea Palazón, R J; Ortiz Pérez, J T; Prat González, S; de Caralt Robira, T M; Cibeira López, M T; Solé Arqués, M

2016-01-01

The development of myocardial fibrosis is a common process in the appearance of ventricular dysfunction in many heart diseases. Magnetic resonance imaging makes it possible to accurately evaluate the structure and function of the heart, and its role in the macroscopic characterization of myocardial fibrosis by late enhancement techniques has been widely validated clinically. Recent studies have demonstrated that T1-mapping techniques can quantify diffuse myocardial fibrosis and the expansion of the myocardial extracellular space in absolute terms. However, further studies are necessary to validate the usefulness of this technique in the early detection of tissue remodeling at a time when implementing early treatment would improve a patient's prognosis. This article reviews the state of the art for T1 mapping of the myocardium, its clinical applications, and its limitations. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Low-dose adenosine stress echocardiography: detection of myocardial viability.

PubMed

Djordjevic-Dikic, Ana; Ostojic, Miodrag; Beleslin, Branko; Nedeljkovic, Ivana; Stepanovic, Jelena; Stojkovic, Sinisa; Petrasinovic, Zorica; Nedeljkovic, Milan; Saponjski, Jovica; Giga, Vojislav

2003-06-03

The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals) echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of >or= 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 +/- 2 months) were available in 24 revascularized patients. Wall motion score index improved from rest 1.55 +/- 0.30 to 1.33 +/- 0.26 at low-dose adenosine (p < 0.001). Of the 257 segments with baseline dyssynergy, adenosine echocardiography identified 122 segments as positive for viability, and 135 as necrotic since no improvement of systolic thickening was observed. Follow-up wall motion score index was 1.31 +/- 0.30 (p < 0.001 vs. rest). The sensitivity of adenosine echo test for identification of viable segments was 87%, while specificity was 95%, and diagnostic accuracy 90%. Positive and negative predictive values were 97% and 80%, respectively. Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability.

Low-dose adenosine stress echocardiography: Detection of myocardial viability

PubMed Central

Djordjevic-Dikic, Ana; Ostojic, Miodrag; Beleslin, Branko; Nedeljkovic, Ivana; Stepanovic, Jelena; Stojkovic, Sinisa; Petrasinovic, Zorica; Nedeljkovic, Milan; Saponjski, Jovica; Giga, Vojislav

2003-01-01

Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals) echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months) were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p < 0.001). Of the 257 segments with baseline dyssynergy, adenosine echocardiography identified 122 segments as positive for viability, and 135 as necrotic since no improvement of systolic thickening was observed. Follow-up wall motion score index was 1.31 ± 0.30 (p < 0.001 vs. rest). The sensitivity of adenosine echo test for identification of viable segments was 87%, while specificity was 95%, and diagnostic accuracy 90%. Positive and negative predictive values were 97% and 80%, respectively. Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability. PMID:12812523

Tenascin-C promotes chronic pressure overload-induced cardiac dysfunction, hypertrophy and myocardial fibrosis.

PubMed

Podesser, Bruno K; Kreibich, Maximilian; Dzilic, Elda; Santer, David; Förster, Lorenz; Trojanek, Sandra; Abraham, Dietmar; Krššák, Martin; Klein, Klaus U; Tretter, Eva V; Kaun, Christoph; Wojta, Johann; Kapeller, Barbara; Gonçalves, Inês Fonseca; Trescher, Karola; Kiss, Attila

2018-04-01

Left ventricular (LV) hypertrophy is characterized by cardiomyocyte hypertrophy and interstitial fibrosis ultimately leading to increased myocardial stiffness and reduced contractility. There is substantial evidence that the altered expression of matrix metalloproteinases (MMP) and Tenascin-C (TN-C) are associated with the progression of adverse LV remodeling. However, the role of TN-C in the development of LV hypertrophy because of chronic pressure overload as well as the regulatory role of TN-C on MMPs remains unknown. In a knockout mouse model of TN-C, we investigated the effect of 10 weeks of pressure overload using transverse aortic constriction (TAC). Cardiac function was determined by magnetic resonance imaging. The expression of MMP-2 and MMP-9, CD147 as well as myocardial fibrosis were assessed by immunohistochemistry. The expression of TN-C was assessed by RT-qPCR and ELISA. TN-C knockout mice showed marked reduction in fibrosis (P < 0.001) and individual cardiomyocytes size (P < 0.01), in expression of MMP-2 (P < 0.05) and MMP-9 (P < 0.001) as well as preserved cardiac function (P < 0.01) in comparison with wild-type mice after 10 weeks of TAC. In addition, CD147 expression was markedly increased under pressure overload (P < 0.01), irrespectively of genotype. TN-C significantly increased the expression of the markers of hypertrophy such as ANP and BNP as well as MMP-2 in H9c2 cells (P < 0.05, respectively). Our results are pointed toward a novel signaling mechanism that contributes to LV remodeling via MMPs upregulation, cardiomyocyte hypertrophy as well as myocardial fibrosis by TN-C under chronic pressure overload.

Treatment of Angina Pectoris Associated with Coronary Microvascular Dysfunction.

PubMed

Ong, Peter; Athanasiadis, Anastasios; Sechtem, Udo

2016-08-01

Treatment of angina pectoris associated with coronary microvascular dysfunction is challenging as the underlying mechanisms are often diverse and overlapping. Patients with type 1 coronary microvascular dysfunction (i.e. absence of epicardial coronary artery disease and myocardial disease) should receive strict control of their cardiovascular risk factors and thus receive statins and ACE-inhibitors in most cases. Antianginal medication consists of ß-blockers and/or calcium channel blockers. Second line drugs are ranolazine and nicorandil with limited evidence. Despite individually titrated combinations of these drugs up to 30 % of patients have refractory angina. Rho-kinase inhibitors and endothelin-receptor antagonists represent potential drugs that may prove useful in these patients in the future.

How and when predictability interacts with accentuation in temporally selective attention during speech comprehension.

PubMed

Li, Xiaoqing; Lu, Yong; Zhao, Haiyan

2014-11-01

The present study used EEG to investigate how and when top-down prediction interacts with bottom-up acoustic signals in temporally selective attention during speech comprehension. Mandarin Chinese spoken sentences were used as stimuli. We systematically manipulated the predictability and de/accentuation of the critical words in the sentence context. Meanwhile, a linguistic attention probe 'ba' was presented concurrently with the critical words or not. The results showed that, first, words with a linguistic attention probe elicited a larger N1 than those without a probe. The latency of this N1 effect was shortened for accented or lowly predictable words, indicating more attentional resources allocated to these words. Importantly, prediction and accentuation showed a complementary interplay on the latency of this N1 effect, demonstrating that when the words had already attracted attention due to low predictability or due to the presence of pitch accent, the other factor did not modulate attention allocation anymore. Second, relative to the lowly predictable words, the highly predictable words elicited a reduced N400 and enhanced gamma-band power increases, especially under the accented conditions; moreover, under the accented conditions, shorter N1 peak-latency was found to correlate with larger gamma-band power enhancement, which indicates that a close relationship might exist between early selective attention and later semantic integration. Finally, the interaction between top-down selective attention (driven by prediction) and bottom-up selective attention (driven by accentuation) occurred before lexical-semantic processing, namely before the N400 effect evoked by predictability, which was discussed with regard to the language comprehension models. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of ranolazine in a model of doxorubicin-induced left ventricle diastolic dysfunction.

PubMed

Cappetta, Donato; Esposito, Grazia; Coppini, Raffaele; Piegari, Elena; Russo, Rosa; Ciuffreda, Loreta Pia; Rivellino, Alessia; Santini, Lorenzo; Rafaniello, Concetta; Scavone, Cristina; Rossi, Francesco; Berrino, Liberato; Urbanek, Konrad; De Angelis, Antonella

2017-11-01

Doxorubicin is a highly effective anticancer drug, but its clinical application is hampered by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of doxorubicin cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent later development of cardiotoxicity is warranted. Increased doxorubicin-dependent ROS may explain, in part, Ca 2+ and Na + overload that contributes to diastolic dysfunction and development of heart failure. Therefore, we tested whether the administration of ranolazine, a selective blocker of late Na + current, immediately after completing doxorubicin therapy, could affect diastolic dysfunction and interfere with the progression of functional decline. Fischer 344 rats received a cumulative dose of doxorubicin of 15 mg·kg -1 over a period of 2 weeks. After the assessment of diastolic dysfunction, the animals were treated with ranolazine (80 mg·kg -1 , daily) for the following 4 weeks. While diastolic and systolic function progressively deteriorated in doxorubicin-treated animals, treatment with ranolazine relieved diastolic dysfunction and prevented worsening of systolic function, decreasing mortality. Ranolazine lowered myocardial NADPH oxidase 2 expression and oxidative/nitrative stress. Expression of the Na + /Ca 2+ exchanger 1 and Na v 1.5 channels was reduced and of the sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase 2 protein was increased. In addition, ranolazine lowered doxorubicin-induced hyper-phosphorylation and oxidation of Ca 2+ /calmodulin-dependent protein kinase II, and decreased myocardial fibrosis. Ranolazine, by the increased Na + influx, induced by doxorubicin, altered cardiac Ca 2+ and Na + handling and attenuated diastolic dysfunction induced by doxorubicin, thus preventing the progression of cardiomyopathy. This article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents

Clinical utility of endocrine markers predicting myocardial siderosis in transfusion dependent thalassemia major.

PubMed

Ehsan, Lubaina; Rashid, Mariam; Alvi, Najveen; Awais, Khadija; Nadeem, Omair; Asghar, Aleezay; Sajjad, Fatimah; Fatima, Malika; Qidwai, Asim; Hussain, Shabneez; Hasan, Erum; Brown, Nick; Altaf, Sadaf; Hasan, Babar; Kirmani, Salman

2018-06-12

Endocrinopathy due to iron overload is the most common morbidity whereas myocardial siderosis causing toxic cardiomyopathy is the leading cause of mortality among patients with transfusion dependent thalassemia major (TDTM). If detected early, this can be treated with aggressive chelation. T2* cardiac magnetic resonance imaging (CMR) guided chelation protocols are now the gold standard but have limited availability in low and middle-income countries. We hypothesized that markers of endocrine dysfunction would correlate with T2* CMR and can be used to predict the severity of myocardial siderosis and guide chelation therapy. We undertook a multicenter retrospective study of 280 patients with TDTM to assess the prevalence of endocrinopathies and the predictive value of a number of individual and composite markers of endocrinopathy with T2* CMR. The prevalence of hypogonadism, stunting, hypoparathyroidism, and hypothyroidism was 82%, 69%, 40%, and 30%, respectively. The sensitivity of hypogonadism and stunting predicting severe myocardial siderosis was 90% and 80%, respectively. We conclude that clinical markers of endocrine dysfunction, especially hypogonadism (positive likelihood ratio [LR+] = 1.4, 95% confidence interval [CI] = 1.0-1.9; positive predictive value [PPV] = 77%, 95% CI = 70-82; negative predictive value [NPV] = 57%, 95% CI = 34-77] and stunting (LR+ = 1.3, 95% CI = 1.1-1.6; PPV = 64%, 95% CI = 60-69; NPV = 55%, 95% CI = 45-64) in TDTM can predict severe myocardial siderosis and can potentially guide chelation therapy, especially where access to T2* CMR is limited. © 2018 Wiley Periodicals, Inc.

Prevalence of scarred and dysfunctional myocardium in patients with heart failure of ischaemic origin: A cardiovascular magnetic resonance study

PubMed Central

2011-01-01

Background Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) can provide unique data on the transmural extent of scar/viability. We assessed the prevalence of dysfunctional myocardium, including partial thickness scar, which could contribute to left ventricular contractile dysfunction in patients with heart failure and ischaemic heart disease who denied angina symptoms. Methods We invited patients with ischaemic heart disease and a left ventricular ejection fraction < 50% by echocardiography to have LGE CMR. Myocardial contractility and transmural extent of scar were assessed using a 17-segment model. Results The median age of the 193 patients enrolled was 70 (interquartile range: 63-76) years and 167 (87%) were men. Of 3281 myocardial segments assessed, 1759 (54%) were dysfunctional, of which 581 (33%) showed no scar, 623 (35%) had scar affecting ≤50% of wall thickness and 555 (32%) had scar affecting > 50% of wall thickness. Of 1522 segments with normal contractile function, only 98 (6%) had evidence of scar on CMR. Overall, 182 (94%) patients had ≥1 and 107 (55%) patients had ≥5 segments with contractile dysfunction that had no scar or ≤50% transmural scar suggesting viability. Conclusions In this cohort of patients with left ventricular systolic dysfunction and ischaemic heart disease, about half of all segments had contractile dysfunction but only one third of these had > 50% of the wall thickness affected by scar, suggesting that most dysfunctional segments could improve in response to an appropriate intervention. PMID:21936915

Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

NASA Technical Reports Server (NTRS)

Koide, M.; Hamawaki, M.; Narishige, T.; Sato, H.; Nemoto, S.; DeFreyte, G.; Zile, M. R.; Cooper G, I. V.; Carabello, B. A.

2000-01-01

BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

Fully automatic left ventricular myocardial strain estimation in 2D short-axis tagged magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Morais, Pedro; Queirós, Sandro; Heyde, Brecht; Engvall, Jan; 'hooge, Jan D.; Vilaça, João L.

2017-09-01

Cardiovascular diseases are among the leading causes of death and frequently result in local myocardial dysfunction. Among the numerous imaging modalities available to detect these dysfunctional regions, cardiac deformation imaging through tagged magnetic resonance imaging (t-MRI) has been an attractive approach. Nevertheless, fully automatic analysis of these data sets is still challenging. In this work, we present a fully automatic framework to estimate left ventricular myocardial deformation from t-MRI. This strategy performs automatic myocardial segmentation based on B-spline explicit active surfaces, which are initialized using an annular model. A non-rigid image-registration technique is then used to assess myocardial deformation. Three experiments were set up to validate the proposed framework using a clinical database of 75 patients. First, automatic segmentation accuracy was evaluated by comparing against manual delineations at one specific cardiac phase. The proposed solution showed an average perpendicular distance error of 2.35  ±  1.21 mm and 2.27  ±  1.02 mm for the endo- and epicardium, respectively. Second, starting from either manual or automatic segmentation, myocardial tracking was performed and the resulting strain curves were compared. It is shown that the automatic segmentation adds negligible differences during the strain-estimation stage, corroborating its accuracy. Finally, segmental strain was compared with scar tissue extent determined by delay-enhanced MRI. The results proved that both strain components were able to distinguish between normal and infarct regions. Overall, the proposed framework was shown to be accurate, robust, and attractive for clinical practice, as it overcomes several limitations of a manual analysis.

Cardiac fibroblast GSK-3β regulates ventricular remodeling and dysfunction in ischemic heart

PubMed Central

Lal, Hind; Ahmad, Firdos; Zhou, Jibin; Yu, Justine E.; Vagnozzi, Ronald J.; Guo, Yuanjun; Yu, Daohai; Tsai, Emily J.; Woodgett, James; Gao, Erhe; Force, Thomas

2014-01-01

Background Myocardial infarction-induced remodeling includes chamber dilatation, contractile dysfunction, and fibrosis. Of these, fibrosis is the least understood. Following MI, activated cardiac fibroblasts (CFs) deposit extracellular matrix. Current therapies to prevent fibrosis are inadequate and new molecular targets are needed. Methods and Results Herein we report that GSK-3β is phosphorylated (inhibited) in fibrotic tissues from ischemic human and mouse heart. Using two fibroblast-specific GSK-3β knockout mouse models, we show that deletion of GSK-3β in CFs leads to fibrogenesis, left ventricular dysfunction and excessive scarring in the ischemic heart. Deletion of GSK-3β induces a pro-fibrotic myofibroblast phenotype in isolated CFs, in post-MI hearts, and in MEFs deleted for GSK-3β. Mechanistically, GSK-3β inhibits pro-fibrotic TGF-β1-SMAD-3 signaling via interactions with SMAD-3. Moreover, deletion of GSK-3β resulted in the suppression of SMAD-3 transcriptional activity. This pathway is central to the pathology since a small molecule inhibitor of SMAD-3 largely prevented fibrosis and limited LV remodeling. Conclusion These studies support targeting GSK-3β in myocardial fibrotic disorders and establish critical roles of CFs in remodeling and ventricular dysfunction. PMID:24899689

Short-term Beneficial Effects of 12 Sessions of Neurofeedback on Avoidant Personality Accentuation in the Treatment of Alcohol Use Disorder

PubMed Central

Dalkner, Nina; Unterrainer, Human F.; Wood, Guilherme; Skliris, Dimitris; Holasek, Sandra J.; Gruzelier, John H.; Neuper, Christa

2017-01-01

This study evaluated the effects of alpha/theta neurofeedback on Clinical Personality Accentuations in individuals with alcohol use disorder. Twenty-five males were investigated using a pre-test/post-test design with a waiting-list control group. Participants were randomly assigned either to an experimental group (n = 13) receiving 12 sessions of neurofeedback twice a week as a treatment adjunct over a period of 6 weeks, or to a control group (n = 12) receiving treatment as usual. The Inventory of Clinical Personality Accentuations and the NEO-Five-Factor Inventory were applied at pre- and post-test. The neurofeedback protocol focused on enhancement of the EEG alpha (8–12 Hz) and theta (4–7 Hz) and used a visual feedback paradigm. Analyses of covariance showed improvements in Avoidant Personality Accentuation within the experimental group. Our data suggest that 12 sessions of this neurofeedback intervention might be effective in reducing avoidant and stress-related personality traits in patients with alcohol use disorder. PMID:29018397

Short-term Beneficial Effects of 12 Sessions of Neurofeedback on Avoidant Personality Accentuation in the Treatment of Alcohol Use Disorder.

PubMed

Dalkner, Nina; Unterrainer, Human F; Wood, Guilherme; Skliris, Dimitris; Holasek, Sandra J; Gruzelier, John H; Neuper, Christa

2017-01-01

This study evaluated the effects of alpha/theta neurofeedback on Clinical Personality Accentuations in individuals with alcohol use disorder. Twenty-five males were investigated using a pre-test/post-test design with a waiting-list control group. Participants were randomly assigned either to an experimental group ( n = 13) receiving 12 sessions of neurofeedback twice a week as a treatment adjunct over a period of 6 weeks, or to a control group ( n = 12) receiving treatment as usual. The Inventory of Clinical Personality Accentuations and the NEO-Five-Factor Inventory were applied at pre- and post-test. The neurofeedback protocol focused on enhancement of the EEG alpha (8-12 Hz) and theta (4-7 Hz) and used a visual feedback paradigm. Analyses of covariance showed improvements in Avoidant Personality Accentuation within the experimental group. Our data suggest that 12 sessions of this neurofeedback intervention might be effective in reducing avoidant and stress-related personality traits in patients with alcohol use disorder.

A TSPO ligand prevents mitochondrial sterol accumulation and dysfunction during myocardial ischemia-reperfusion in hypercholesterolemic rats.

PubMed

Musman, Julien; Paradis, Stéphanie; Panel, Mathieu; Pons, Sandrine; Barau, Caroline; Caccia, Claudio; Leoni, Valerio; Ghaleh, Bijan; Morin, Didier

2017-10-15

A major cause of cell death during myocardial ischemia-reperfusion is mitochondrial dysfunction. We previously showed that the reperfusion of an ischemic myocardium was associated with an accumulation of cholesterol into mitochondria and a concomitant strong generation of auto-oxidized oxysterols. The inhibition of mitochondrial accumulation of cholesterol abolished the formation of oxysterols and prevented mitochondrial injury at reperfusion. The aim of this study was to investigate the impact of hypercholesterolemia on sterol and oxysterol accumulation in rat cardiac cytosols and mitochondria and to analyse the effect of the translocator protein ligand 4'-chlorodiazepam on this accumulation and mitochondrial function. Hypercholesterolemic ZDF fa/fa rats or normocholesterolemic lean rats were submitted to 30min of coronary artery occlusion followed by 15min reperfusion where cardiac cytosols and mitochondria were isolated. Hypercholesterolemia increased the cellular cardiac concentrations of cholesterol, cholesterol precursors and oxysterols both in cytosol and mitochondria in non-ischemic conditions. It also amplified the accumulation of all these compounds in cardiac cells and the alteration of mitochondrial function with ischemia-reperfusion. Administration of 4'-chlorodiazepam to ZDF fa/fa rats had no effect on the enhancement of sterols and oxysterols observed in the cytosols but inhibited cholesterol transfer to the mitochondria. It also alleviated the mitochondrial accumulation of all the investigated sterols and oxysterols. This was associated with a restoration of oxidative phosphorylation and a prevention of mitochondrial transition pore opening. The inhibition of cholesterol accumulation with TSPO ligands represents an interesting strategy to protect the mitochondria during ischemia-reperfusion in hypercholesterolemic conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Aerobic exercise training delays cardiac dysfunction and improves autonomic control of circulation in diabetic rats undergoing myocardial infarction.

PubMed

Rodrigues, Bruno; Jorge, Luciana; Mostarda, Cristiano T; Rosa, Kaleizu T; Medeiros, Alessandra; Malfitano, Christiane; de Souza, Alcione L; Viegas, Katia Aparecida da Silva; Lacchini, Silvia; Curi, Rui; Brum, Patricia C; De Angelis, Kátia; Irigoyen, Maria Cláudia

2012-09-01

Exercise training (ET) has been used as a nonpharmacological strategy for treatment of diabetes and myocardial infarction (MI) separately. We evaluated the effects ET on functional and molecular left ventricular (LV) parameters as well as on autonomic function and mortality in diabetics after MI. Male Wistar rats were divided into control (C), sedentary-diabetic infarcted (SDI), and trained-diabetic infarcted (TDI) groups. MI was induced after 15 days of streptozotocin-diabetes induction. Seven days after MI, the trained group underwent ET protocol (90 days, 50-70% maximal oxygen consumption-VO(2)max). LV function was evaluated noninvasively and invasively; baroreflex sensitivity, pulse interval variability, cardiac output, tissue blood flows, VEGF mRNA and protein, HIF1-α mRNA, and Ca(2+) handling proteins were measured. MI area was reduced in TDI (21 ± 4%) compared with SDI (38 ± 4%). ET induced improvement in cardiac function, hemodynamics, and tissue blood flows. These changes were probable consequences of a better expression of Ca(2+) handling proteins, increased VEGF mRNA and protein expression as well as improvement in autonomic function, that resulted in reduction of mortality in TDI (33%) compared with SDI (68%) animals. ET reduced cardiac and peripheral dysfunction and preserved autonomic control in diabetic infarcted rats. Consequently, these changes resulted in improved VO(2)max and survival after MI. Copyright © 2012 Elsevier Inc. All rights reserved.

Assessment of Left Ventricular Myocardial Viability by 3-Dimensional Speckle-Tracking Echocardiography in Patients With Myocardial Infarction.

PubMed

Ran, Hong; Zhang, Ping-Yang; Zhang, You-Xiang; Zhang, Jian-Xin; Wu, Wen-Fang; Dong, Jing; Ma, Xiao-Wu

2016-08-01

area strain with a cutoff of 23.2% had sensitivity of 91.5% and specificity of 82.8%. Three-dimensional speckle-tracking echocardiography might have potential for detection of myocardial viability in patients with cardiac dysfunction due to MI.

Prognostic Value of the Thrombolysis in Myocardial Infarction Risk Score in ST-Elevation Myocardial Infarction Patients With Left Ventricular Dysfunction (from the EPHESUS Trial).

PubMed

Popovic, Batric; Girerd, Nicolas; Rossignol, Patrick; Agrinier, Nelly; Camenzind, Edoardo; Fay, Renaud; Pitt, Bertram; Zannad, Faiez

2016-11-15

The Thrombolysis in Myocardial Infarction (TIMI) risk score remains a robust prediction tool for short-term and midterm outcome in the patients with ST-elevation myocardial infarction (STEMI). However, the validity of this risk score in patients with STEMI with reduced left ventricular ejection fraction (LVEF) remains unclear. A total of 2,854 patients with STEMI with early coronary revascularization participating in the randomized EPHESUS (Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial were analyzed. TIMI risk score was calculated at baseline, and its predictive value was evaluated using C-indexes from Cox models. The increase in reclassification of other variables in addition to TIMI score was assessed using the net reclassification index. TIMI risk score had a poor predictive accuracy for all-cause mortality (C-index values at 30 days and 1 year ≤0.67) and recurrent myocardial infarction (MI; C-index values ≤0.60). Among TIMI score items, diabetes/hypertension/angina, heart rate >100 beats/min, and systolic blood pressure <100 mm Hg were inconsistently associated with survival, whereas none of the TIMI score items, aside from age, were significantly associated with MI recurrence. Using a constructed predictive model, lower LVEF, lower estimated glomerular filtration rate (eGFR), and previous MI were significantly associated with all-cause mortality. The predictive accuracy of this model, which included LVEF and eGFR, was fair for both 30-day and 1-year all-cause mortality (C-index values ranging from 0.71 to 0.75). In conclusion, TIMI risk score demonstrates poor discrimination in predicting mortality or recurrent MI in patients with STEMI with reduced LVEF. LVEF and eGFR are major factors that should not be ignored by predictive risk scores in this population. Copyright © 2016 Elsevier Inc. All rights reserved.

Myocardial Bridge

MedlinePlus

... Center > Myocardial Bridge Menu Topics Topics FAQs Myocardial Bridge En español Your heart is made of muscle, ... surface of the heart. What is a myocardial bridge? A myocardial bridge is a band of heart ...

Toll-like receptor 3 plays a role in myocardial infarction and ischemia/reperfusion injury.

PubMed

Lu, Chen; Ren, Danyang; Wang, Xiaohui; Ha, Tuanzhu; Liu, Li; Lee, Eric J; Hu, Jing; Kalbfleisch, John; Gao, Xiang; Kao, Race; Williams, David; Li, Chuanfu

2014-01-01

Innate immune and inflammatory responses mediated by Toll like receptors (TLRs) have been implicated in myocardial ischemia/reperfusion (I/R) injury. This study examined the role of TLR3 in myocardial injury induced by two models, namely, myocardial infarction (MI) and I/R. First, we examined the role of TLR3 in MI. TLR3 deficient (TLR3(-/-)) and wild type (WT) mice were subjected to MI induced by permanent ligation of the left anterior descending (LAD) coronary artery for 21days. Cardiac function was measured by echocardiography. Next, we examined whether TLR3 contributes to myocardial I/R injury. TLR3(-/-) and WT mice were subjected to myocardial ischemia (45min) followed by reperfusion for up to 3days. Cardiac function and myocardial infarct size were examined. We also examined the effect of TLR3 deficiency on I/R-induced myocardial apoptosis and inflammatory cytokine production. TLR3(-/-) mice showed significant attenuation of cardiac dysfunction after MI or I/R. Myocardial infarct size and myocardial apoptosis induced by I/R injury were significantly attenuated in TLR3(-/-) mice. TLR3 deficiency increases B-cell lymphoma 2 (BCL2) levels and attenuates I/R-increased Fas, Fas ligand or CD95L (FasL), Fas-Associated protein with Death Domain (FADD), Bax and Bak levels in the myocardium. TLR3 deficiency also attenuates I/R-induced myocardial nuclear factor KappaB (NF-κB) binding activity, Tumor necrosis factor alpha (TNF-α) and Interleukin-1 beta (IL-1β) production as well as I/R-induced infiltration of neutrophils and macrophages into the myocardium. TLR3 plays an important role in myocardial injury induced by MI or I/R. The mechanisms involve activation of apoptotic signaling and NF-κB binding activity. Modulation of TLR3 may be an effective approach for ameliorating heart injury in heart attack patients. © 2013.

Dipeptidyl peptidase 4 inhibitor attenuates obesity-induced myocardial fibrosis by inhibiting transforming growth factor-βl and Smad2/3 pathways in high-fat diet-induced obesity rat model.

PubMed

Hong, Seul-Ki; Choo, Eun-Ho; Ihm, Sang-Hyun; Chang, Kiyuk; Seung, Ki-Bae

2017-11-01

Obesity-induced myocardial fibrosis may lead to diastolic dysfunction and ultimately heart failure. Activation of the transforming growth factor (TGF)-βl and its downstream Smad2/3 pathways may play a pivotal role in the pathogenesis of obesity-induced myocardial fibrosis, and the antidiabetic dipeptidyl peptidase 4 inhibitors (DPP4i) might affect these pathways. We investigated whether DPP4i reduces myocardial fibrosis by inhibiting the TGF-β1 and Smad2/3 pathways in the myocardium of a diet-induced obesity (DIO) rat model. Eight-week-old male spontaneously hypertensive rats (SHRs) were fed either a normal fat diet (chow) or a high-fat diet (HFD) and then the HFD-fed SHRs were randomized to either the DPP4i (MK-0626) or control (distilled water) groups for 12weeks. At 20weeks old, all the rats underwent hemodynamic and metabolic studies and Doppler echocardiography. Compared with the normal fat diet (chow)-fed SHRs, the HFD-fed SHRs developed a more intense degree of hyperglycemia and dyslipidemia and showed a constellation of left ventricular (LV) diastolic dysfunction, and exacerbated myocardial fibrosis, as well as activation of the TGF-β1 and Smad2/3 pathways. DPP4i significantly improved the metabolic and hemodynamic parameters. The echocardiogram showed that DPP4i improved the LV diastolic dysfunction (early to late ventricular filling velocity [E/A] ratio, 1.49±0.21 vs. 1.77±0.09, p<0.05). Furthermore, DPP4i significantly reduced myocardial fibrosis and collagen production by the myocardium and suppressed TGF-β1 and phosphorylation of Smad2/3 in the heart. In addition, DPP4i decreased TGF-β1-induced collagen production and TGF-β1-mediated phosphorylation and nuclear translocation of Smad2/3 in rat cardiac fibroblasts. In conclusion, DPP4 inhibition attenuated myocardial fibrosis and improved LV diastolic dysfunction in a DIO rat model by modulating the TGF-β1 and Smad2/3 pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduction of N terminal-pro-brain (B-type) natriuretic peptide levels with exercise-based cardiac rehabilitation in patients with left ventricular dysfunction after myocardial infarction.

PubMed

Giallauria, Francesco; De Lorenzo, Anna; Pilerci, Francesco; Manakos, Athanasio; Lucci, Rosa; Psaroudaki, Marianna; D'Agostino, Mariantonietta; Del Forno, Domenico; Vigorito, Carlo

2006-08-01

N-terminal-pro-brain (B-type) natriuretic peptide (NT-pro-BNP) is a peptide hormone released from ventricles in response to myocyte stretch. The aim of the study was to investigate the influence of exercise training on plasma NT-pro-BNP to verify if this parameter could be used as a biological marker of left ventricular remodelling in myocardial infarction patients undergoing an exercise training programme. Forty-four patients after myocardial infarction were enrolled into a cardiac rehabilitation programme, and were randomized in two groups of 22 patients each. Group A patients followed a 3-month exercise training programme, while group B patients received only routine recommendations. All patients underwent NT-pro-BNP assay, and cardiopulmonary exercise test before hospital discharge and after 3 months. In Group A, exercise training reduced NT-pro-BNP levels (from 1498+/-438 to 470+/-375 pg/ml, P=0.0026), increased maximal (VO2peak+4.3+/-2.9 ml/kg per min, P<0.001; Powermax+38+/-7, P<0.001) exercise parameters and work efficiency (Powermax/VO2peak+1.3+/-0.4 Power/ml per kg per min, P<0.001); there was also an inverse correlation between changes in NT-pro-BNP levels and in VO2peak (r=-0.72, P<0.001), E-wave (r=-0.51, P<0.001) and E/A ratio (r=0.59, P<0.001). In group B, at 3 months, no changes were observed in NT-pro-BNP levels, exercise and echocardiographic parameters. Three months exercise training in patients with moderate left ventricular systolic dysfunction after myocardial infarction induced a reduction in NT-pro-BNP levels, an improvement of exercise capacity and early left ventricular diastolic filling, without negative left ventricular remodelling. Whether the reduction of NT-pro-BNP levels could be useful as a surrogate marker of favourable left ventricular remodelling at a later follow-up remains to be further explored.

Myocardial Rupture in Acute Myocardial Infarction: Mechanistic Explanation Based on the Ventricular Myocardial Band Hypothesis.

PubMed

Vargas-Barron, Jesús; Antunez-Montes, Omar-Yassef; Roldán, Francisco-Javier; Aranda-Frausto, Alberto; González-Pacheco, Hector; Romero-Cardenas, Ángel; Zabalgoitia, Miguel

2015-01-01

Torrent-Guasp explains the structure of the ventricular myocardium by means of a helical muscular band. Our primary purpose was to demonstrate the utility of echocardiography in human and porcine hearts in identifying the segments of the myocardial band. The second purpose was to evaluate the relation of the topographic distribution of the myocardial band with some post-myocardial infarction ruptures. Five porcine and one human heart without cardiopathy were dissected and the ventricular myocardial segments were color-coded for illustration and reconstruction purposes. These segments were then correlated to the conventional echocardiographic images. Afterwards in three cases with post-myocardial infarction rupture, a correlation of the topographic location of the rupture with the distribution of the ventricular band was made. The human ventricular band does not show any differences from the porcine band, which confirms the similarities of the four segments; these segments could be identified by echocardiography. In three cases with myocardial rupture, a correlation of the intra-myocardial dissection with the distribution of the ventricular band was observed. Echocardiography is helpful in identifying the myocardial band segments as well as the correlation with the topographic distribution of some myocardial post-infarction ruptures.

Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy.

PubMed

von Lueder, Thomas G; Wang, Bing H; Kompa, Andrew R; Huang, Li; Webb, Randy; Jordaan, Pierre; Atar, Dan; Krum, Henry

2015-01-01

Angiotensin receptor neprilysin inhibitors (ARNi), beyond blocking angiotensin II signaling, augment natriuretic peptides by inhibiting their breakdown by neprilysin. The myocardial effects of ARNi have been little studied until recently. We hypothesized that LCZ696 attenuates left ventricular (LV) remodeling after experimental myocardial infarction (MI), and that this may be contributed to by inhibition of hypertrophy and fibrosis in cardiac cells. One week after MI, adult male Sprague-Dawley rats were randomized to treatment for 4 weeks with LCZ696 (68 mg/kg body weight perorally; MI-ARNi, n=11) or vehicle (MI-vehicle, n=6). Five weeks after MI, MI-ARNi versus MI-vehicle demonstrated lower LV end-diastolic diameter (by echocardiography; 9.7±0.2 versus 10.5±0.3 mm), higher LV ejection fraction (60±2 versus 47±5%), diastolic wall strain (0.23±0.02 versus 0.13±0.02), and circular strain (-9.8±0.5 versus -7.3±0.5%; all P<0.05). LV pressure-volume loops confirmed improved LV function. Despite similar infarct size, MI-ARNi versus MI-vehicle had lower cardiac weights (P<0.01) and markedly reduced fibrosis in peri-infarct and remote myocardium. Angiotensin II-stimulated incorporation of 3[H]leucine in cardiac myocytes and 3[H]proline in cardiac fibroblast was used to evaluate hypertrophy and fibrosis, respectively. The neprilysin inhibitor component of LCZ696, LBQ657, inhibited hypertrophy but not fibrosis. The angiotensin receptor blocker component of LCZ696, valsartan inhibited both hypertrophy and fibrosis. Dual valsartan+LBQ augmented the inhibitory effects of valsartan and the highest doses completely abrogated angiotensin II-mediated effects. LCZ696 attenuated cardiac remodeling and dysfunction after MI. This may be contributed to by superior inhibition of LCZ696 on cardiac fibrosis and cardiac hypertrophy than either stand-alone neprilysin inhibitor or angiotensin receptor blocker. © 2014 American Heart Association, Inc.

Mangiferin protect myocardial insults through modulation of MAPK/TGF-β pathways.

PubMed

Suchal, Kapil; Malik, Salma; Gamad, Nanda; Malhotra, Rajiv Kumar; Goyal, Sameer N; Ojha, Shreesh; Kumari, Santosh; Bhatia, Jagriti; Arya, Dharamvir Singh

2016-04-05

Mangiferin, a xanthone glycoside isolated from leaves of Mangifera indica (Anacardiaceae) is known to modulate many biological targets in inflammation and oxidative stress. The present study was designed to investigate whether mangiferin exerts protection against myocardial ischemia-reperfusion (IR) injury and possible role of Mitogen Activated Protein Kinase (MAPKs) and Transforming Growth Factor-β (TGF-β) pathways in its cardioprotection. Male albino Wistar rats were treated with mangiferin (40 mg/kg, i.p.) for 15 days. At the end of the treatment protocol, rats were subjected to IR injury consisting of 45 min ischemia followed by 1h reperfusion. IR-control rats caused significant cardiac dysfunction, increased serum cardiac injury markers, lipid peroxidation and a significant decrease in tissue antioxidants as compared to sham group. Histopathological examination of IR rats revealed myocardial necrosis, edema and infiltration of inflammatory cells. However, pretreatment with mangiferin significantly restored myocardial oxidant-antioxidant status, maintained membrane integrity, and attenuated the levels of proinflammatory cytokines, pro-apoptotic proteins and TGF-β. Furthermore, mangiferin significantly reduced the phosphorylation of p38, and JNK and enhanced phosphorylation of ERK1/2. These results suggest that mangiferin protects against myocardial IR injury by modulating MAPK mediated inflammation and apoptosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Myocardial strain estimation from CT: towards computer-aided diagnosis on infarction identification

NASA Astrophysics Data System (ADS)

Wong, Ken C. L.; Tee, Michael; Chen, Marcus; Bluemke, David A.; Summers, Ronald M.; Yao, Jianhua

2015-03-01

Regional myocardial strains have the potential for early quantification and detection of cardiac dysfunctions. Although image modalities such as tagged and strain-encoded MRI can provide motion information of the myocardium, they are uncommon in clinical routine. In contrary, cardiac CT images are usually available, but they only provide motion information at salient features such as the cardiac boundaries. To estimate myocardial strains from a CT image sequence, we adopted a cardiac biomechanical model with hyperelastic material properties to relate the motion on the cardiac boundaries to the myocardial deformation. The frame-to-frame displacements of the cardiac boundaries are obtained using B-spline deformable image registration based on mutual information, which are enforced as boundary conditions to the biomechanical model. The system equation is solved by the finite element method to provide the dense displacement field of the myocardium, and the regional values of the three principal strains and the six strains in cylindrical coordinates are computed in terms of the American Heart Association nomenclature. To study the potential of the estimated regional strains on identifying myocardial infarction, experiments were performed on cardiac CT image sequences of ten canines with artificially induced myocardial infarctions. The leave-one-subject-out cross validations show that, by using the optimal strain magnitude thresholds computed from ROC curves, the radial strain and the first principal strain have the best performance.

Targeted P2X7 R shRNA delivery attenuates sympathetic nerve sprouting and ameliorates cardiac dysfunction in rats with myocardial infarction.

PubMed

Gao, Hongmei; Yin, Jie; Shi, Yugen; Hu, Hesheng; Li, Xiaolu; Xue, Mei; Cheng, Wenjuan; Wang, Ye; Li, Xinran; Li, Yongkang; Wang, Yu; Yan, Suhua

2017-04-01

Inflammation-dominated sympathetic sprouting adjacent to the necrotic region following myocardial infarction (MI) has been implicated in the etiology of arrhythmias resulting in sudden cardiac death; however, the mechanisms responsible remain to be elucidated. Although P2X 7 R is a key immune mediator, its role has yet to be explored. We investigated whether P2X 7 R regulates NF-κB and affects cardiac sympathetic reinnervation in rats undergoing MI. An adenoviral vector with a short hairpin RNA (shRNA) sequence inserted was adopted for the inhibition of P2X 7 R in vivo. Myocardial infarction was induced by left coronary artery ligation, and immediately after that, recombinant P2X 7 R-shRNA adenovirus, negative adenovirus (control), or normal saline solution (vehicle) was injected intramyocardially around the MI region and border areas. A high level of P2X 7 R was activated in the infarcted tissue at an early stage. The administration of P2X 7 R RNAi resulted in the inhibition of Akt and Erk1/2 phosphorylation and decreased the activation of NF-κB and macrophage infiltration, as well as attenuated the expression of nerve growth factor (NGF). Eventually, the NGF-induced sympathetic hyperinnervation was blunted, as assessed by the immunofluorescence of tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP 43). At 7 days post-MI, the arrhythmia score of programmed electrical stimulation in the vehicle-treated infarcted rats was higher than the MI-shRNA group. Further amelioration of cardiac dysfunction was also detected. The administration of P2X 7 R RNAi during the acute inflammatory response phase prevented the process of sympathetic hyperinnervation after MI, which was associated in part with inhibiting the Akt and ERK1/2 pathways and NF-κB activation. © 2016 John Wiley & Sons Ltd.

The role of myocardial viability in contemporary cardiac practice.

PubMed

Jamiel, Abdelrahman; Ebid, Mohamad; Ahmed, Amjad M; Ahmed, Dalia; Al-Mallah, Mouaz H

2017-07-01

Ischemic heart disease (IHD) remains the single most common cause of death worldwide. Ischemic cardiomyopathy is a major sequel of coronary artery disease. The economic health burden of IHD is substantial. In patients with old myocardial infarction (OMI), the extent of viable myocardium (VM) directly affects the short- and long-term outcome. There is a considerable collection of observational data showing substantial improvement in patients with significant left ventricular dysfunction when the need for revascularization is guided by preoperative assessment of viability and hibernation. However, a major challenge for present cardiovascular imaging is to identify better ways to assess viable but inadequately perfused myocardium and thus optimize selection of patients for coronary revascularization. Several non-invasive techniques have been developed to detect signs of viability. Hence, our aim is to provide the reader a state-of-the art review for the assessment of myocardial viability.

Coronary Microvascular Dysfunction is Related to Abnormalities in Myocardial Structure and Function in Cardiac Amyloidosis

PubMed Central

Dorbala, Sharmila; Vangala, Divya; Bruyere, John; Quarta, Christina; Kruger, Jenna; Padera, Robert; Foster, Courtney; Hanley, Michael; Di Carli, Marcelo F.; Falk, Rodney

2014-01-01

Objectives We sought to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis. Background Effort angina is common in subjects with cardiac amyloidosis even in the absence of epicardial coronary artery disease (CAD). Methods Thirty one subjects were prospectively enrolled in this study including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2D echocardiography. Global LV myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF / rest MBF) adjusting for rest rate pressure product. Results Compared to the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 vs. 0.88 ± 0.23 ml/g/min, P = 0.004), stress MBF (0.85 ± 0.29 vs. 1.85 ± 0.45 vs. ml/min/g, P < 0.0001), CFR (1.19 ± 0.38 vs. 2.23 ± 0.88, P < 0.0001), and higher minimal coronary vascular resistance (111 ± 40 vs. 70 ± 19 mm Hg/mL/g/min, P = 0.004). Of note, almost all amyloid subjects (> 95%) demonstrated significantly reduced peak stress MBF (< 1.3 mL/g/min). In multivariable linear regression analyses, a diagnosis of amyloidosis, increased LV mass and age were the only independent predictors of impaired coronary vasodilator function. Conclusions Coronary microvascular dysfunction is highly prevalent in subjects with cardiac amyloidosis even in the absence of epicardial CAD, and may explain their anginal symptoms. Further study is required to understand whether specific therapy directed at amyloidosis may improve coronary vasomotion in amyloidosis. PMID:25023822

Dynamic stimuli: accentuating aesthetic preference biases.

PubMed

Friedrich, Trista E; Harms, Victoria L; Elias, Lorin J

2014-01-01

Despite humans' preference for symmetry, artwork often portrays asymmetrical characteristics that influence the viewer's aesthetic preference for the image. When presented with asymmetrical images, aesthetic preference is often given to images whose content flows from left-to-right and whose mass is located on the right of the image. Cerebral lateralization has been suggested to account for the left-to-right directionality bias; however, the influence of cultural factors, such as scanning habits, on aesthetic preference biases is debated. The current research investigates aesthetic preference for mobile objects and landscapes, as previous research has found contrasting preference for the two image types. Additionally, the current experiment examines the effects of dynamic movement on directionality preference to test the assumption that static images are perceived as aesthetically equivalent to dynamic images. After viewing mirror-imaged pairs of pictures and videos, right-to-left readers failed to show a preference bias, whereas left-to-right readers preferred stimuli with left-to-right directionality regardless of the location of the mass. The directionality bias in both reading groups was accentuated by the videos, but the bias was significantly stronger in left-to-right readers. The findings suggest that scanning habits moderate the leftward bias resulting from hemispheric specialization and that dynamic stimuli further fluent visual processing.

Relationship of myocardial hibernation, scar, and angiographic collateral flow in ischemic cardiomyopathy with coronary chronic total occlusion.

PubMed

Wang, Li; Lu, Min-Jie; Feng, Lei; Wang, Juan; Fang, Wei; He, Zuo-Xiang; Dou, Ke-Fei; Zhao, Shi-Hua; Yang, Min-Fu

2018-03-07

The relationship between myocardial viability and angiographic collateral flow is not fully elucidated in ischemic cardiomyopathy (ICM) with coronary artery chronic total occlusion (CTO). We aimed to clarify the relationship between myocardial hibernation, myocardial scar, and angiographic collateral flow in these patients. Seventy-one consecutive ICM patients with 122 CTOs and 652 dysfunctional segments within CTO territories were retrospectively analyzed. Myocardial hibernation (perfusion-metabolism mismatch) and the extent of 18 F-fluorodeoxyglucose (FDG) abnormalities were assessed using 99m Tc-sestamibi and 18 F-FDG imaging. Myocardial scar was evaluated by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. Collateral flow observed on coronary angiography was assessed using Rentrop classification. In these patients, neither the extent nor frequency of myocardial hibernation or scar was related to the status of collateral flow. Moreover, the matching rate in determining myocardial viability was poor between any 2 imaging indices. The extent of 18 F-FDG abnormalities was linearly related to the extent of LGE rather than myocardial hibernation. Of note, nearly one-third (30.4%) of segments with transmural scar still had hibernating tissue. Hibernation and non-transmural scar had higher sensitivity (63.0% and 66.7%) than collateral flow (37.0%) in predicting global functional improvement. Angiographic collateral cannot accurately predict myocardial viability, and has lower sensitivity in prediction of functional improvement in CTO territories in ICM patients. Hence, assessment of myocardial viability with non-invasive imaging modalities is of importance. Moreover, due to the lack of correlation between myocardial hibernation and scar, these two indices are complementary but not interchangeable.

Predictors of transient left ventricular dysfunction following transcatheter patent ductus arteriosus closure in pediatric age.

PubMed

Agha, Hala Mounir; Hamza, Hala S; Kotby, Alyaa; Ganzoury, Mona E L; Soliman, Nanies

2017-10-01

To evaluate the left ventricular function before and after transcatheter percutaneous patent ductus arteriosus (PDA) closure, and to identify the predictors of myocardial dysfunction post-PDA closure if present. Transcatheter PDA closure; conventional, Doppler, and tissue Doppler imaging; and speckle tracking echocardiography. To determine the feasibility and reliability of tissue Doppler and myocardial deformation imaging for evaluating myocardial function in children undergoing transcatheter PDA closure. Forty-two children diagnosed with hemodynamically significant PDA underwent percutaneous PDA closure. Conventional, Doppler, and tissue Doppler imaging, and speckle-derived strain rate echocardiography were performed at preclosure and at 48 hours, 1 month, and 6 months postclosure. Tissue Doppler velocities of the lateral and septal mitral valve annuli were obtained. Global and regional longitudinal peak systolic strain values were determined using two-dimensional speckle tracking echocardiography. The median age of the patients was 2 years and body weight was 15 kg, with the mean PDA diameter of 3.11 ± 0.99 mm. M-mode measurements (left ventricular end diastolic diameter, left atrium diameter to aortic annulus ratio, ejection fraction, and shortening fraction) reduced significantly early after PDA closure ( p  < 0.001). After 1 month, left ventricular end diastolic diameter and left atrium diameter to aortic annulus ratio continued to decrease, while ejection fraction and fractional shortening improved significantly. All tissue Doppler velocities showed a significant decrease at 48 hours with significant prolongation of global myocardial function ( p  < 0.001) and then were normalized within 1 month postclosure. Similarly, global longitudinal strain significantly decreased at 48 hours postclosure ( p  < 0.001), which also recovered at 1 month follow-up. Preclosure global longitudinal strain showed a good correlation with the postclosure

Assessment of left ventricular functions and myocardial iron load with tissue Doppler and speckle tracking echocardiography and T2* MRI in patients with β-thalassemia major.

PubMed

Ari, Mehmet Emre; Ekici, Filiz; Çetin, İbrahim İlker; Tavil, Emine Betül; Yaralı, Neşe; Işık, Pamir; Hazırolan, Tuncay; Tunç, Bahattin

2017-03-01

The purpose of this study is to determine early myocardial dysfunction in β-thalassemia major (BTM) patients. Where the myocardial dysfunction cannot be detected by conventional echocardiography, it could be detected by tissue Doppler imaging (TDI) or speckle tracking echocardiography (STE). In this study, we analyzed 60 individuals, 30 of whom were BTM patients and the other 30 of whom were the control group. T2* magnetic resonance imaging (MRI) was used to measure cardiac iron deposition. The myocardial functions were evaluated by conventional echocardiography, TDI and STE. When basal lateral left ventricular and basal septal wall TDI values were compared between the patient group and control group, only isovolumic contraction time values were significantly longer in the patients. The global circumferential strain was significantly lower in the patients. When evaluated as segmental, longitudinal strain values of basal inferoseptum and circumferential strain values of anteroseptum, anterior, and inferolateral segments were significantly lower in the patients. In the patients, global longitudinal and circumferential strains in the group who had pathological T2* values were significantly lower than the group who did not. In addition, circumferential strain values in anteroseptum, anterolateral, inferior, and inferoseptum segments were significantly lower in the patients with T2* values<20 ms than those with T2* values≥20 ms. Although T2* MRI is the most sensitive test detecting myocardial iron load, TDI and STE can be used for screening myocardial dysfunction. The abnormal strain values, especially circumferential, may be detected as the first finding of abnormal iron load and related to T2* values. © 2017, Wiley Periodicals, Inc.

How long-term memory and accentuation interact during spoken language comprehension.

PubMed

Li, Xiaoqing; Yang, Yufang

2013-04-01

Spoken language comprehension requires immediate integration of different information types, such as semantics, syntax, and prosody. Meanwhile, both the information derived from speech signals and the information retrieved from long-term memory exert their influence on language comprehension immediately. Using EEG (electroencephalogram), the present study investigated how the information retrieved from long-term memory interacts with accentuation during spoken language comprehension. Mini Chinese discourses were used as stimuli, with an interrogative or assertive context sentence preceding the target sentence. The target sentence included one critical word conveying new information. The critical word was either highly expected or lowly expected given the information retrieved from long-term memory. Moreover, the critical word was either consistently accented or inconsistently de-accented. The results revealed that for lowly expected new information, inconsistently de-accented words elicited a larger N400 and larger theta power increases (4-6 Hz) than consistently accented words. In contrast, for the highly expected new information, consistently accented words elicited a larger N400 and larger alpha power decreases (8-14 Hz) than inconsistently de-accented words. The results suggest that, during spoken language comprehension, the effect of accentuation interacted with the information retrieved from long-term memory immediately. Moreover, our results also have important consequences for our understanding of the processing nature of the N400. The N400 amplitude is not only enhanced for incorrect information (new and de-accented word) but also enhanced for correct information (new and accented words). Copyright © 2013 Elsevier Ltd. All rights reserved.

Left ventricular diastolic dysfunction in type 2 diabetes patients: a novel 2D strain analysis based on cardiac magnetic resonance imaging.

PubMed

Chen, Qiang; Gan, Yan; Li, Zhi-Yong

2016-09-01

This study was to develop a strain analysis method to evaluate the left ventricular (LV) functions in type 2 diabetic patients with an asymptomatic LV diastolic dysfunction. Two groups (10 asymptomatic type 2 diabetic subjects and 10 control ones) were considered. All of the subjects had normal ejection fraction values but impaired diastolic functions assessed by the transmitral blood flow velocity. For each subject, based on cardiac MRI, global indexes including LV volume, LV myocardial mass, cardiac index (CI), and transmitral peak velocity, were measured, and regional indexes (i.e., LV deformation, strain and strain rate) were calculated through an image-registration technology. Most of the global indexes did not differentiate between the two groups, except for the CI, LV myocardial mass and transmitral peak velocity. While for the regional indexes, the global LV diastolic dysfunction of the diabetic indicated an increased strain (0.08 ± 0.044 vs. -0.031 ± 0.077, p = 0.001) and a reduced strain rate (1.834 ± 0.909 vs. 3.791 ± 2.394, p = 0.033) compared to the controls, moreover, the local LV diastolic dysfunction reflected by the strain and strain rate varied, and the degree of dysfunction gradually decreased from the basal level to the apical level. The results showed that the strain and strain rates are effective to capture the subtle alterations of the LV functions, and the proposed method can be used to estimate the LV myocardial function based on cardiac MRI.

Pannus-related prosthetic valve dysfunction. Case report

PubMed Central

MOLDOVAN, MARIA-SÎNZIANA; BEDELEANU, DANIELA; KOVACS, EMESE; CIUMĂRNEAN, LORENA; MOLNAR, ADRIAN

2016-01-01

Pannus-related prosthetic valve dysfunction, a complication of mechanical prosthetic valve replacement, is rare, with a slowly progressive evolution, but it can be acute, severe, requiring surgical reintervention. We present the case of a patient with a mechanical single disc aortic prosthesis, with moderate prosthesis-patient mismatch, minor pannus found on previous ultrasound examinations, who presented to our service with angina pain with a duration of 1 hour, subsequently interpreted as non-ST segment elevation myocardial infarction (NSTEMI) syndrome. Coronarography showed normal epicardial coronary arteries, an ample movement of the prosthetic disc, without evidence of coronary thromboembolism, and Gated Single-Photon Emission Computerized Tomography (SPECT) with Technetium (Tc)-99m detected no perfusion defects. Transthoracic echocardiography (TTE) evidenced a dysfunctional prosthesis due to a subvalvular mass; transesophageal echocardiography (TOE) showed the interference of this mass, with a pannus appearance, with the closure of the prosthetic disc. Under conditions of repeated angina episodes, under anticoagulant treatment, surgery was performed, with the intraoperative confirmation of pannus and its removal. Postoperative evolution was favorable. This case reflects the diagnostic and therapeutic management problems of pannus-related prosthetic valve dysfunction. PMID:27004041

Pannus-related prosthetic valve dysfunction. Case report.

PubMed

Moldovan, Maria-Sînziana; Bedeleanu, Daniela; Kovacs, Emese; Ciumărnean, Lorena; Molnar, Adrian

2016-01-01

Pannus-related prosthetic valve dysfunction, a complication of mechanical prosthetic valve replacement, is rare, with a slowly progressive evolution, but it can be acute, severe, requiring surgical reintervention. We present the case of a patient with a mechanical single disc aortic prosthesis, with moderate prosthesis-patient mismatch, minor pannus found on previous ultrasound examinations, who presented to our service with angina pain with a duration of 1 hour, subsequently interpreted as non-ST segment elevation myocardial infarction (NSTEMI) syndrome. Coronarography showed normal epicardial coronary arteries, an ample movement of the prosthetic disc, without evidence of coronary thromboembolism, and Gated Single-Photon Emission Computerized Tomography (SPECT) with Technetium (Tc)-99m detected no perfusion defects. Transthoracic echocardiography (TTE) evidenced a dysfunctional prosthesis due to a subvalvular mass; transesophageal echocardiography (TOE) showed the interference of this mass, with a pannus appearance, with the closure of the prosthetic disc. Under conditions of repeated angina episodes, under anticoagulant treatment, surgery was performed, with the intraoperative confirmation of pannus and its removal. Postoperative evolution was favorable. This case reflects the diagnostic and therapeutic management problems of pannus-related prosthetic valve dysfunction.

Magnetic Resonance Characterization of Cardiac Adaptation and Myocardial Fibrosis in Pulmonary Hypertension Secondary to Systemic-To-Pulmonary Shunt.

PubMed

Pereda, Daniel; García-Lunar, Inés; Sierra, Federico; Sánchez-Quintana, Damián; Santiago, Evelyn; Ballesteros, Constanza; Encalada, Juan F; Sánchez-González, Javier; Fuster, Valentín; Ibáñez, Borja; García-Álvarez, Ana

2016-09-01

Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are strong predictors of morbidity and mortality among patients with congenital heart disease. Early detection of RV involvement may be useful in the management of these patients. We aimed to assess progressive cardiac adaptation and quantify myocardial extracellular volume in an experimental porcine model of PH because of aorto-pulmonary shunt using cardiac magnetic resonance (CMR). To characterize serial cardiac adaptation, 12 pigs (aorto-pulmonary shunt [n=6] or sham operation [n=6]) were evaluated monthly with right heart catheterization, CMR, and computed tomography during 4 months, followed by pathology analysis. Extracellular volume by CMR in different myocardial regions was studied in 20 animals (aorto-pulmonary shunt [n=10] or sham operation [n=10]) 3 months after the intervention. All shunted animals developed PH. CMR evidenced progressive RV hypertrophy and dysfunction secondary to increased afterload and left ventricular dilatation secondary to volume overload. Shunt flow by CMR strongly correlated with PH severity, left ventricular end-diastolic pressure, and left ventricular dilatation. T1-mapping sequences demonstrated increased extracellular volume at the RV insertion points, the interventricular septum, and the left ventricular lateral wall, reproducing the pattern of fibrosis found on pathology. Extracellular volume at the RV insertion points strongly correlated with pulmonary hemodynamics and RV dysfunction. Prolonged systemic-to-pulmonary shunting in growing piglets induces PH with biventricular remodeling and myocardial fibrosis that can be detected and monitored using CMR. These results may be useful for the diagnosis and management of congenital heart disease patients with pulmonary overcirculation. © 2016 American Heart Association, Inc.

Myocardial oedema as the sole marker of acute injury in Takotsubo cardiomyopathy: a cardiovascular magnetic resonance (CMR) study.

PubMed

Iacucci, Ilaria; Carbone, Iacopo; Cannavale, Giuseppe; Conti, Bettina; Iampieri, Ilaria; Rosati, Riccardo; Sardella, Gennaro; Frustaci, Andrea; Fedele, Francesco; Catalano, Carlo; Francone, Marco

2013-12-01

The main hallmark of Takotsubo cardiomyopathy (TT-CMP) is transient ischaemia, with completely reversible regional contractile dysfunction, which involves the mid-apical segments and shows no angiographic signs of coronary artery disease (CAD). The acute and reversible myocardial injury suggests that tissue oedema may be an important marker of disease. Seventeen patients with a clinical and angiographic diagnosis of TT-CMP underwent cardiovascular magnetic resonance (CMR) imaging in the acute phase and at follow-up after 4 months. A standard acquisition protocol including turbo spin echo (TSE) T2-weighted short-tau inversion-recovery (T2 STIR), steady-state free-precession cine (SSFP cine) and lateenhancement (LE) imaging after gadolinium benzyloxypropionic tetraacetic acid (Gd-BOPTA) administration was performed. All images were analysed, and data on oedema and LE were correlated with regional dysfunction and histological findings from endomyocardial biopsy (EMB) where available. In all patients, T2 STIR images showed a diffuse homogeneous hyperintensity that extended to all mid-apical segments and perfectly matched the area of regional dysfunction, reflecting tissue oedema. In the five patients who underwent EMB, histology confirmed the massive interstitial oedema associated with typical contraction-band necrosis. No cases of LE were observed. At follow-up, complete regression of oedema was observed in all cases, with significant recovery of regional and global left ventricular (LV) function (ejection fraction from 48.7% to 59.8%). Myocardial oedema on CMR is a characteristic feature of acute TT-CMP, which reflects acute inflammation and acute myocardial injury. It could therefore be used as a specific marker of disease severity.

Cardiovascular magnetic resonance assessment of ventricular function and myocardial scarring before and early after repair of anomalous left coronary artery from the pulmonary artery

PubMed Central

2014-01-01

Background In patients with anomalous left coronary artery from the pulmonary artery (ALCAPA) left ventricular (LV) dilatation and dysfunction evolves due to diminished myocardial perfusion caused by coronary steal phenomenon. Using late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) imaging, myocardial scarring has been shown in ALCAPA patients late after repair, however the incidence of scarring before surgery and its impact on postoperative course after surgical repair remained unknown. Methods 8 ALCAPA-patients (mean age 10.0 ± 5.8 months) underwent CMR before and early after (mean 4.9 ± 2.5 months) coronary reimplantation procedures. CMR included functional analysis and LGE for detection of myocardial scars. Results LV dilatation (mean LVEDVI 171 ± 94 ml/m2) and dysfunction (mean LV-EF 22 ± 10 %) was present in all patients and improved significantly after surgery (mean LVEDV 68 ± 42 ml/m2, p = 0.02; mean LV-EF 58 ± 19 %, p < 0.001). Preoperative CMR revealed myocardial scarring in 2 of the 8 patients and did not predict postoperative course. At follow-up CMR, one LGE-positive patient showed delayed recovery of LV function while myocardial scarring was still present in both patients. In two patients new-onset transmural scarring was found, although functional recovery after operation was sufficient. One of them showed a stenosis of the left coronary artery and required resurgery. Conclusions Despite diminished myocardial perfusion and severely compromised LV function, myocardial scarring was preoperatively only infrequently present. Improvement of myocardial function was independent of new-onset scarring while the impact of preoperative scarring still needs to be defined. PMID:24387660

Long-Term Preservation of Left Ventricular Systolic Function in Patients With Refractory Angina Pectoris and Inducible Myocardial Ischemia on Optimal Medical Therapy.

PubMed

Slavich, Massimo; Maranta, Francesco; Fumero, Andrea; Godino, Cosmo; Giannini, Francesco; Oppizzi, Michele; Colombo, Antonio; Fragasso, Gabriele; Margonato, Alberto

2016-05-15

Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function. Copyright © 2016 Elsevier Inc. All rights reserved.

Early myocardial damage assessment in dystrophinopathies using (99)Tc(m)-MIBI gated myocardial perfusion imaging.

PubMed

Zhang, Li; Liu, Zhe; Hu, Ke-You; Tian, Qing-Bao; Wei, Ling-Ge; Zhao, Zhe; Shen, Hong-Rui; Hu, Jing

2015-01-01

Early detection of muscular dystrophy (MD)-associated cardiomyopathy is important because early medical treatment may slow cardiac remodeling and attenuate symptoms of cardiac dysfunction; however, no sensitive and standard diagnostic method for MD at an earlier stage has been well-recognized. Thus, the aim of this study was to test the early diagnostic value of technetium 99m-methoxyisobutylisonitrile ((99)Tc(m)-MIBI) gated myocardial perfusion imaging (G-MPI) for MD. Ninety-one patients underwent (99)Tc(m)-MIBI G-MPI examinations when they were diagnosed with Duchenne muscular dystrophy (DMD) (n=77) or Becker muscular dystrophy (BMD; n=14). (99)Tc(m)-MIBI G-MPI examinations were repeated in 43 DMD patients who received steroid treatments for 2 years as a follow-up examination. Myocardial defects were observed in nearly every segment of the left ventricular wall in both DMD and BMD patients compared with controls, especially in the inferior walls and the apices by using (99)Tc(m)-MIBI G-MPI. Cardiac wall movement impairment significantly correlated with age in the DMD and BMD groups (r s=0.534 [P<0.05] and r s=0.784 [P<0.05], respectively). Intermittent intravenous doses of glucocorticoids and continuation with oral steroid treatments significantly improved myocardial function in DMD patients (P<0.05), but not in BMD patients. (99)Tc(m)-MIBI G-MPI is a sensitive and safe approach for early evaluation of cardiomyopathy in patients with DMD or BMD, and can serve as a candidate method for the evaluation of progression, prognosis, and assessment of the effect of glucocorticoid treatment in these patients.

Non-ischemic diabetic cardiomyopathy may initially exhibit a transient subclinical phase of hyperdynamic myocardial performance.

PubMed

Hensel, Kai O

2016-09-01

Cardiovascular complications are the key cause for mortality in diabetes mellitus. Besides ischemia-related cardiac malfunction there is growing evidence for non-ischemic diabetes-associated heart failure in both type 1 and type 2 diabetes mellitus. The underlying pathophysiology of non-ischemic diabetic cardiomyopathy (NIDC) is poorly understood and data on myocardial mechanics in early stages of the disease are rare. However, several studies in both human and experimental animal settings have reported prima facie unexplained features indicating myocardial hyperdynamics early in the course of the disease. The new hypothesis is that - other than previously thought - NIDC may be non-linear and initially feature an asymptomatic subclinical phase of myocardial hypercontractility that precedes the long-term development of diabetes-associated cardiac dysfunction and ultimately heart failure. Diabetes-induced metabolic imbalances may lead to a paradoxic inotropic increase and inefficient myocardial mechanics that finally result in a gradual deterioration of myocardial performance. In conclusion, diabetic patients should be screened regularly and early in the course of the disease utilizing ultra-sensitive myocardial deformation imaging in order to identify patients at risk for diabetes-associated heart failure. Moreover, hyperdynamic myocardial deformation might help distinguish non-ischemic from ischemic diabetic cardiomyopathy. Further studies are needed to illuminate the underlying pathophysiological mechanisms, the exact spatiotemporal evolvement of diabetic cardiomyopathy and its long-term relation to clinical outcome parameters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline.

PubMed

da Luz, Vinicius Fernando; Otsuki, Denise Aya; Gonzalez, Maria Margarita Castro; Negri, Elnara Marcia; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Malbouisson, Luiz Marcelo Sá; Viana, Bruno Gonçalves; Vane, Matheus Fachini; Carmona, Maria Jose Carvalho

2015-10-01

The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline. © 2015 Wiley Publishing Asia Pty Ltd.

Accentuated antagonism in vagal heart rate control mediated through muscarinic potassium channels.

PubMed

Mizuno, Masaki; Kamiya, Atsunori; Kawada, Toru; Miyamoto, Tadayoshi; Shimizu, Shuji; Shishido, Toshiaki; Sugimachi, Masaru

2008-12-01

Although muscarinic K(+) (K(ACh)) channels contribute to a rapid heart rate (HR) response to vagal stimulation, whether background sympathetic tone affects the HR control via the K(ACh)channels remains to be elucidated. In seven anesthetized rabbits with sinoaortic denervation and vagotomy, we estimated the dynamic transfer function of the HR response by using random binary vagal stimulation (0-10 Hz). Tertiapin, a selective K(ACh) channel blocker, decreased the dynamic gain (to 2.3+/- 0.9 beats.min(-1).Hz(-1), from 4.6+/- 1.1, P < 0.01, mean+/- SD) and the corner frequency (to 0.05+/- 0.01 Hz, from 0.26+/- 0.04, P < 0.01). Under 5 Hz tonic cardiac sympathetic stimulation (CSS), tertiapin decreased the dynamic gain (to 3.6+/- 1.0 beats.min(-1).Hz(-1), from 7.3+/- 1.1, P < 0.01) and the corner frequency (to 0.06+/- 0.02 Hz, from 0.23+/- 0.06, P < 0.01). Two-way analysis of variance indicated significant interaction between the tertiapin and CSS effects on the dynamic gain. In contrast, no significant interactions were observed between the tertiapin and CSS effects on the corner frequency and the lag time. In conclusion, although a cyclic AMP-dependent mechanism has been well established, an accentuated antagonism also occurred in the direct effect of ACh via the K(ACh) channels. The rapidity of the HR response obtained by the K(ACh) channel pathway was robust during the accentuated antagonism.

Mental Stress-Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction: Sex Differences and Mechanisms.

PubMed

Vaccarino, Viola; Sullivan, Samaah; Hammadah, Muhammad; Wilmot, Kobina; Al Mheid, Ibhar; Ramadan, Ronnie; Elon, Lisa; Pimple, Pratik M; Garcia, Ernest V; Nye, Jonathon; Shah, Amit J; Alkhoder, Ayman; Levantsevych, Oleksiy; Gay, Hawkins; Obideen, Malik; Huang, Minxuan; Lewis, Tené T; Bremner, J Douglas; Quyyumi, Arshed A; Raggi, Paolo

2018-02-20

Mental stress-induced myocardial ischemia (MSIMI) is frequent in patients with coronary artery disease and is associated with worse prognosis. Young women with a previous myocardial infarction (MI), a group with unexplained higher mortality than men of comparable age, have shown elevated rates of MSIMI, but the mechanisms are unknown. We studied 306 patients (150 women and 156 men) ≤61 years of age who were hospitalized for MI in the previous 8 months and 112 community controls (58 women and 54 men) frequency matched for sex and age to the patients with MI. Endothelium-dependent flow-mediated dilation and microvascular reactivity (reactive hyperemia index) were measured at rest and 30 minutes after mental stress. The digital vasomotor response to mental stress was assessed using peripheral arterial tonometry. Patients received 99m Tc-sestamibi myocardial perfusion imaging at rest, with mental (speech task) and conventional (exercise/pharmacological) stress. The mean age of the sample was 50 years (range, 22-61). In the MI group but not among controls, women had a more adverse socioeconomic and psychosocial profile than men. There were no sex differences in cardiovascular risk factors, and among patients with MI, clinical severity tended to be lower in women. Women in both groups showed a higher peripheral arterial tonometry ratio during mental stress but a lower reactive hyperemia index after mental stress, indicating enhanced microvascular dysfunction after stress. There were no sex differences in flow-mediated dilation changes with mental stress. The rate of MSIMI was twice as high in women as in men (22% versus 11%, P =0.009), and ischemia with conventional stress was similarly elevated (31% versus 16%, P =0.002). Psychosocial and clinical risk factors did not explain sex differences in inducible ischemia. Although vascular responses to mental stress (peripheral arterial tonometry ratio and reactive hyperemia index) also did not explain sex differences in

Penehyclidine hydrochloride regulates mitochondrial dynamics and apoptosis through p38MAPK and JNK signal pathways and provides cardioprotection in rats with myocardial ischemia-reperfusion injury.

PubMed

Feng, Min; Wang, Lirui; Chang, Siyuan; Yuan, Pu

2018-05-31

The potential mechanism of penehyclidine hydrochloride (PHC) against myocardial ischemia-reperfusion (I/R) injury has not been fully elucidated. The aim of the present study was to reveal whether mitochondrial dynamics, apoptosis, and MAPKs were involved in the cardioprotective effect of this drug on myocardial I/R injury. Ninety healthy adult male Wistar rats were separately pretreated with normal saline (0.9%); PHC; and signal pathway blockers of MAPKs, Drp1, and Bcl-2. Coronary artery ligation and subsequent reperfusion were performed to induce myocardial I/R injury. Echocardiography was performed. Myocardial enzymes and oxidative stress markers were detected. Myocardial cell apoptotic rates and infarct sizes were measured. Mitochondrial function was evaluated. Expression levels of MAPKs, mitochondria regulatory proteins (Drp1, Mfn1/2), and apoptosis-related proteins (Bcl-2, Bax) were determined. PHC pretreatment improved myocardial abnormalities (dysfunction, injury, infarct size, and apoptotic rate), mitochondrial abnormalities (dysfunction and fission), and excessive oxidative stress and inhibited the activities of p38MAPK and JNK signal pathways in rats with myocardial I/R injury (P < 0.05). Additionally, p38MAPK and JNK blockers (SB239063 and SP600125, respectively) had an effect on rats same as that of PHC. Although Drp1 blocker (Mdivi-1) showed a similar cardioprotective effect (P < 0.05), it did not affect the expression of MAPKs and apoptosis-related proteins (P > 0.05). In addition, Bcl-2 blocker (ABT-737) caused a high expression of Drp1 and a low expression of Mfn1/2 (P < 0.05). PHC regulated mitochondrial dynamics and apoptosis through p38MAPK and JNK signal pathways and provided cardioprotection in rats with myocardial I/R injury. Copyright © 2018 Elsevier B.V. All rights reserved.

Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

PubMed Central

Wang, Li-li; Miller, Dori; Wanders, Desiree; Nanayakkara, Gayani; Amin, Rajesh; Judd, Robert; Morrison, Edward E; Zhong, Ju-ming

2016-01-01

Aim: Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. Methods: Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- and 9-weeks following fistula. The protein expression of adiponectin, adiponectin receptors (AdipoR1/R2 and T-cadherin) and AMPK activity were measured using Western blot analyses. Isolated ventricular myocytes were prepared at 12 weeks post-fistula to examine the contractile performance of myocytes and intracellular Ca2+ transient. Results: A-V fistula resulted in significant reductions in serum and myocardial adiponectin levels, myocardial adiponectin receptor (AdipoR1/R2 and T-cadherin) levels, as well as myocardial AMPK activity. Consistent with these changes, the isolated myocytes exhibited significant depression in cell shortening and intracellular Ca2+ transient. Administration of adenoviral adiponectin significantly increased serum adiponectin levels and prevented myocyte contractile dysfunction in fistula rats. Furthermore, pretreatment of isolated myocytes with recombinant adiponectin (2.5 μg/mL) significantly improved their contractile performance in fistula rats, but had no effects in control or adenoviral adiponectin-administered rats. Conclusion: These results demonstrate a positive correlation between adiponectin downregulation and volume overload-induced ventricular remodeling. Adiponectin plays a protective role in volume overload-induced heart failure. PMID:26616727

Increased intracranial pressure elicits hypertension, increased sympathetic activity, electrocardiographic abnormalities and myocardial damage in rats.

PubMed

Shanlin, R J; Sole, M J; Rahimifar, M; Tator, C H; Factor, S M

1988-09-01

Intracranial pressure was increased in 59 rats by inflating a subdural balloon to a total mass volume of 0.3 ml. The increase in intracranial pressure ranged from 75 to greater than 500 mm Hg. With few exceptions, mean arterial pressure increased to as high as 227 mm Hg during the increase in intracranial pressure. Significant increases in plasma catecholamines, major electrocardiographic changes and a considerably shortened survival time were observed only in the rats that demonstrated an increase in mean arterial pressure greater than 50 mm Hg. A perfusion study with liquid silicone rubber (Microfil) revealed dilated irregular myocardial vessels with areas of focal constriction consistent with microvascular spasm. Histologic examination of the myocardium revealed widespread patches of contraction band necrosis and occasional contraction bands in the smooth muscle media of large coronary arteries. These observations suggest that myocardial damage after suddenly increased intracranial pressure resulted both from exposure to toxic levels of catecholamines and from myocardial reperfusion. Extension of these studies to humans suggests that a detailed assessment of myocardial function should be performed in victims of severe brain injury. Myocardial dysfunction may be a major determinant of the patient's prognosis or may render the heart unsuitable for transplantation.

[Character accentuations as a criterion for psychological risks in the professional activity of the builders of main gas pipelines in the conditions of arctic].

PubMed

Korneeva, Ia A; Simonova, N N

2015-01-01

The article is devoted to the study of character accentuations as a criterion for psychological risks in the professional activity of builders of main gas pipelines in the conditions of Arctic. to study the severity of character accentuations in rotation-employed builders of main gas pipelines, stipulated by their professional activities, as well as personal resources to overcome these destructions. The study involved 70 rotation-employed builders of trunk pipelines, working in the Tyumen Region (duration of the shift-in--52 days), aged from 23 to 59 (mean age 34,9 ± 8.1) years, with the experience of work from 0.5 years to 14 years (the average length of 4.42 ± 3.1). Methods of the study: questionnaires, psychological testing, participant observation. One-Sample t-test of Student, multiple regression analysis, incremental analysis. In the work there were revealed differences of expression of character accentuations in builders of trunk pipelines with experience in work on rotation less and more than five years. There was determined that builders of the main gas pipelines, working on the rotation in Arctic, with more pronounced accentuation ofthe character use mainly psychological defenses of compensation, substitution and denial, and have an average level of expression of flexibility as the regulatory process.

Mineralocorticoid receptor antagonists modulate galectin-3 and interleukin-33/ST2 signaling in left ventricular systolic dysfunction after acute myocardial infarction.

PubMed

Lax, Antonio; Sanchez-Mas, Jesus; Asensio-Lopez, Maria C; Fernandez-Del Palacio, Maria J; Caballero, Luis; Garrido, Iris P; Pastor-Perez, Francisco J; Januzzi, James L; Pascual-Figal, Domingo A

2015-01-01

This study aimed to evaluate the specific role of the 2 available mineralocorticoid receptor antagonists (MRAs), eplerenone and spironolactone, on the modulation of galectin-3 (Gal-3) and interleukin (IL)-33/ST2 signaling in an experimental model of left ventricular systolic dysfunction after acute myocardial infarction (MI). The molecular mechanisms of benefits of MRAs in patients with left ventricular systolic dysfunction after MI not well understood. MI and left ventricular systolic dysfunction were induced by permanent ligation of the anterior coronary artery in 45 male Wistar rats, randomly assigned to no therapy (MI group, n = 15) or to receive MRAs (100 mg/kg/day) for 4 weeks; either eplerenone (n = 15) or spironolactone (n = 15) was used. A sham group was used as a control (n = 8). Elements of the pathway for Gal-3 including transforming growth factor (TGF)-β and SMAD3, as well as that for IL-33/ST2 (including IL-33 and soluble ST2 [sST2]) were analyzed in the infarcted and noninfarcted myocardium by quantitative real-time reverse transcription polymerase chain reaction. Expression of markers of fibrosis (collagen types I and III, tissue inhibitor of metalloproteinase-1) and inflammation (IL-6, tumor necrosis factor-α, monocyte chemotactic protein-1) was also examined. In the infarcted myocardium, compared with sham animals, the MI group had higher concentrations of Gal-3, TGF-β, SMAD3, IL-33, and sST2, as well as higher concentrations of markers of fibrosis and inflammation. Treatment with MRAs down-regulated Gal-3, TGF-β, and SMAD3 and enhanced IL-33/ST2 signaling with lower expression of sST2; protective IL-33 up-regulation was unaffected by MRAs. Modulation of Gal-3 and IL-33/ST2 signaling induced by MRAs correlated with lower expression levels of fibrosis and inflammatory markers. No differences were found between eplerenone and spironolactone. In the noninfarcted myocardium, compared with sham animals, the MI group exhibited a higher expression of

Daily exercise prevents diastolic dysfunction and oxidative stress in a female mouse model of western diet induced obesity by maintaining cardiac heme oxygenase-1 levels.

PubMed

Bostick, Brian; Aroor, Annayya R; Habibi, Javad; Durante, William; Ma, Lixin; DeMarco, Vincent G; Garro, Mona; Hayden, Melvin R; Booth, Frank W; Sowers, James R

2017-01-01

Obesity is a global epidemic with profound cardiovascular disease (CVD) complications. Obese women are particularly vulnerable to CVD, suffering higher rates of CVD compared to non-obese females. Diastolic dysfunction is the earliest manifestation of CVD in obese women but remains poorly understood with no evidence-based therapies. We have shown early diastolic dysfunction in obesity is associated with oxidative stress and myocardial fibrosis. Recent evidence suggests exercise may increase levels of the antioxidant heme oxygenase-1 (HO-1). Accordingly, we hypothesized that diastolic dysfunction in female mice consuming a western diet (WD) could be prevented by daily volitional exercise with reductions in oxidative stress, myocardial fibrosis and maintenance of myocardial HO-1 levels. Four-week-old female C57BL/6J mice were fed a high-fat/high-fructose WD for 16weeks (N=8) alongside control diet fed mice (N=8). A separate cohort of WD fed females was allowed a running wheel for the entire study (N=7). Cardiac function was assessed at 20weeks by high-resolution cardiac magnetic resonance imaging (MRI). Functional assessment was followed by immunohistochemistry, transmission electron microscopy (TEM) and Western blotting to identify pathologic mechanisms and assess HO-1 protein levels. There was no significant body weight decrease in exercising mice, normalized body weight 14.3g/mm, compared to sedentary mice, normalized body weight 13.6g/mm (p=0.38). Total body fat was also unchanged in exercising, fat mass of 6.6g, compared to sedentary mice, fat mass 7.4g (p=0.55). Exercise prevented diastolic dysfunction with a significant reduction in left ventricular relaxation time to 23.8ms for exercising group compared to 33.0ms in sedentary group (p<0.01). Exercise markedly reduced oxidative stress and myocardial fibrosis with improved mitochondrial architecture. HO-1 protein levels were increased in the hearts of exercising mice compared to sedentary WD fed females. This

Differential expression of myocardial heat shock proteins in rats acutely exposed to fluoride.

PubMed

Panneerselvam, Lakshmikanthan; Raghunath, Azhwar; Perumal, Ekambaram

2017-09-01

Acute fluoride (F - ) toxicity is known to cause severe cardiac complications and leads to sudden heart failure. Previously, we reported that increased myocardial oxidative damage, apoptosis, altered cytoskeleton and AMPK signaling proteins associated with energy deprivation in acute F - induced cardiac dysfunction. The present study was aimed to decipher the status of myocardial heat shock proteins (Hsps-Hsp27, Hsp32, Hsp40, Hsp60, Hsp70, Hsp90) and heat shock transcription factor 1 (Hsf1) in acute F - -intoxicated rats. In order to study the expression of myocardial Hsps, male Wistar rats were treated with single oral doses of 45 and 90 mg/kg F - for 24 h. The expression levels of myocardial Hsps were determined using RT-PCR, western blotting, and immunohistochemical studies. Acute F - -intoxicated rats showed elevated levels of both the transcripts and protein expression of Hsf1, Hsp27, Hsp32, Hsp60, and Hsp70 when compared to control. In addition, the expression levels of Hsp40 and Hsp90 were significantly declined in a dose-dependent fashion in F - -treated animals. Our result suggests that differential expression of Hsps in the rat myocardium could serve as a balance between pro-survival and death signal during acute F - -induced heart failure.

Association between left ventricular perfusion defects and myocardial deformation indexes in heart transplantation recipients.

PubMed

D'Andrea, Antonello; De Rimini, Maria Luisa; America, Raffaella; Cirillo, Chiara; Riegler, Lucia; Limongelli, Giuseppe; D'Alto, Michele; Salerno, Gemma; Maiello, Ciro; Muto, Pietro; Russo, Maria Giovanna; Calabrò, Raffaele; Bossone, Eduardo; Pacileo, Giuseppe

2017-10-01

The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P<.001). Such relationships underline STE ability to early identify HTx pts with subclinical myocardial dysfunction during long-term follow-up. © 2017, Wiley Periodicals, Inc.

Myocardial Autophagy after Severe Burn in Rats

PubMed Central

Zhang, Qiong; Shi, Xiao-hua; Huang, Yue-sheng

2012-01-01

Background Autophagy plays a major role in myocardial ischemia and hypoxia injury. The present study investigated the effects of autophagy on cardiac dysfunction in rats after severe burn. Methods Protein expression of the autophagy markers LC3 and Beclin 1 were determined at 0, 1, 3, 6, and 12 h post-burn in Sprague Dawley rats subjected to 30% total body surface area 3rd degree burns. Autophagic, apoptotic, and oncotic cell death were evaluated in the myocardium at each time point by immunofluorescence. Changes of cardiac function were measured in a Langendorff model of isolated heart at 6 h post-burn, and the autophagic response was measured following activation by Rapamycin and inhibition by 3-methyladenine (3-MA). The angiotensin converting enzyme inhibitor enalaprilat, the angiotensin receptor I blocker losartan, and the reactive oxygen species inhibitor diphenylene iodonium (DPI) were also applied to the ex vivo heart model to examine the roles of these factors in post-burn cardiac function. Results Autophagic cell death was first observed in the myocardium at 3 h post-burn, occurring in 0.008 ± 0.001% of total cardiomyocytes, and continued to increase to a level of 0.022 ± 0.005% by 12 h post-burn. No autophagic cell death was observed in control hearts. Compared with apoptosis, autophagic cell death occurred earlier and in larger quantities. Rapamycin enhanced autophagy and decreased cardiac function in isolated hearts 6 h post-burn, while 3-MA exerted the opposite response. Enalaprilat, losartan, and DPI all inhibited autophagy and enhanced heart function. Conclusion Myocardial autophagy is enhanced in severe burns and autophagic cell death occurred early at 3 h post-burn, which may contribute to post-burn cardiac dysfunction. Angiotensin II and reactive oxygen species may play important roles in this process by regulating cell signaling transduction. PMID:22768082

Myocardial pathology induced by aldosterone is dependent on non-canonical activities of G protein-coupled receptor kinases

PubMed Central

Cannavo, Alessandro; Liccardo, Daniela; Eguchi, Akito; Elliott, Katherine J.; Traynham, Christopher J.; Ibetti, Jessica; Eguchi, Satoru; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe; Koch, Walter J.

2016-01-01

Hyper-aldosteronism is associated with myocardial dysfunction including induction of cardiac fibrosis and maladaptive hypertrophy. Mechanisms of these cardiotoxicities are not fully understood. Here we show that mineralocorticoid receptor (MR) activation by aldosterone leads to pathological myocardial signalling mediated by mitochondrial G protein-coupled receptor kinase 2 (GRK2) pro-death activity and GRK5 pro-hypertrophic action. Moreover, these MR-dependent GRK2 and GRK5 non-canonical activities appear to involve cross-talk with the angiotensin II type-1 receptor (AT1R). Most importantly, we show that ventricular dysfunction caused by chronic hyper-aldosteronism in vivo is completely prevented in cardiac Grk2 knockout mice (KO) and to a lesser extent in Grk5 KO mice. However, aldosterone-induced cardiac hypertrophy is totally prevented in Grk5 KO mice. We also show human data consistent with MR activation status in heart failure influencing GRK2 levels. Therefore, our study uncovers GRKs as targets for ameliorating pathological cardiac effects associated with high-aldosterone levels. PMID:26932512

Anti-inflammatory therapies in myocardial infarction: failures, hopes and challenges.

PubMed

Huang, Shuaibo; Frangogiannis, Nikolaos G

2018-05-01

In the infarcted heart, the damage-associated molecular pattern proteins released by necrotic cells trigger both myocardial and systemic inflammatory responses. Induction of chemokines and cytokines and up-regulation of endothelial adhesion molecules mediate leukocyte recruitment in the infarcted myocardium. Inflammatory cells clear the infarct of dead cells and matrix debris and activate repair by myofibroblasts and vascular cells, but may also contribute to adverse fibrotic remodelling of viable segments, accentuate cardiomyocyte apoptosis and exert arrhythmogenic actions. Excessive, prolonged and dysregulated inflammation has been implicated in the pathogenesis of complications and may be involved in the development of heart failure following infarction. Studies in animal models of myocardial infarction (MI) have suggested the effectiveness of pharmacological interventions targeting the inflammatory response. This article provides a brief overview of the cell biology of the post-infarction inflammatory response and discusses the use of pharmacological interventions targeting inflammation following infarction. Therapy with broad anti-inflammatory and immunomodulatory agents may also inhibit important repair pathways, thus exerting detrimental actions in patients with MI. Extensive experimental evidence suggests that targeting specific inflammatory signals, such as the complement cascade, chemokines, cytokines, proteases, selectins and leukocyte integrins, may hold promise. However, clinical translation has proved challenging. Targeting IL-1 may benefit patients with exaggerated post-MI inflammatory responses following infarction, not only by attenuating adverse remodelling but also by stabilizing the atherosclerotic plaque and by inhibiting arrhythmia generation. Identification of the therapeutic window for specific interventions and pathophysiological stratification of MI patients using inflammatory biomarkers and imaging strategies are critical for optimal

Mitochondrial JNK activation triggers autophagy and apoptosis and aggravates myocardial injury following ischemia/reperfusion.

PubMed

Xu, Jie; Qin, Xinghua; Cai, Xiaoqing; Yang, Lu; Xing, Yuan; Li, Jun; Zhang, Lihua; Tang, Ying; Liu, Jiankang; Zhang, Xing; Gao, Feng

2015-02-01

c-Jun N-terminal kinase (JNK) is a stress-activated mitogen-activated protein kinase that plays a central role in initiating apoptosis in disease conditions. Recent studies have shown that mitochondrial JNK signaling is partly responsible for ischemic myocardial dysfunction; however, the underlying mechanism remains unclear. Here we report for the first time that activation of mitochondrial JNK, rather than JNK localization on mitochondria, induces autophagy and apoptosis and aggravates myocardial ischemia/reperfusion injury. Myocardial ischemia/reperfusion induced a dominant increase of mitochondrial JNK phosphorylation, while JNK mitochondrial localization was reduced. Treatment with Tat-SabKIM1, a retro-inverso peptide which blocks JNK interaction with mitochondria, decreased mitochondrial JNK activation without affecting JNK mitochondrial localization following reperfusion. Tat-SabKIM1 treatment reduced Bcl2-regulated autophagy, cytochrome c-mediated apoptosis and myocardial infarct size. Notably, selective inhibition of mitochondrial JNK activation using Tat-SabKIM1 produced a similar infarct size-reducing effect as inhibiting universal JNK activation with JNK inhibitor SP600125. Moreover, insulin-treated animals exhibited significantly dampened mitochondrial JNK activation accompanied by reduced infarct size and diminished autophagy and apoptosis following reperfusion. Taken together, these findings demonstrate that mitochondrial JNK activation, rather than JNK mitochondrial localization, induces autophagy and apoptosis and exacerbates myocardial ischemia/reperfusion injury. Insulin selectively inhibits mitochondrial JNK activation, contributing to insulin cardioprotection against myocardial ischemic/reperfusion injury. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Cardiomyocyte specific expression of Acyl-coA thioesterase 1 attenuates sepsis induced cardiac dysfunction and mortality

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

Xia, Congying; Dong, Ruolan; Chen, Chen

Compromised cardiac fatty acid oxidation (FAO) induced energy deprivation is a critical cause of cardiac dysfunction in sepsis. Acyl-CoA thioesterase 1 (ACOT1) is involved in regulating cardiac energy production via altering substrate metabolism. This study aims to clarify whether ACOT1 has a potency to ameliorate septic myocardial dysfunction via enhancing cardiac FAO. Transgenic mice with cardiomyocyte specific expression of ACOT1 (αMHC-ACOT1) and their wild type (WT) littermates were challenged with Escherichia coli lipopolysaccharide (LPS; 5 mg/kg i.p.) and myocardial function was assessed 6 h later using echocardiography and hemodynamics. Deteriorated cardiac function evidenced by reduction of the percentage of left ventricular ejectionmore » fraction and fractional shortening after LPS administration was significantly attenuated by cardiomyocyte specific expression of ACOT1. αMHC-ACOT1 mice exhibited a markedly increase in glucose utilization and cardiac FAO compared with LPS-treated WT mice. Suppression of cardiac peroxisome proliferator activated receptor alpha (PPARa) and PPARγ-coactivator-1α (PGC1a) signaling observed in LPS-challenged WT mice was activated by the presence of ACOT1. These results suggest that ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction, possibly through activating PPARa/PGC1a signaling. - Highlights: • ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction. • ACOT1 can regulate PPARa/PGC1a signaling pathway. • We first generate the transgenic mice with cardiomyocyte specific expression of ACOT1.« less

Mesenchymal stem cells with overexpression of midkine enhance cell survival and attenuate cardiac dysfunction in a rat model of myocardial infarction.

PubMed

Zhao, Shu-Li; Zhang, Yao-Jun; Li, Ming-Hui; Zhang, Xin-Lei; Chen, Shao-Liang

2014-03-17

Elevated midkine (MK) expression may contribute to ventricular remodeling and ameliorate cardiac dysfunction after myocardial infarction (MI). Ex vivo modification of signaling mechanisms in mesenchymal stem cells (MSCs) with MK overexpression may improve the efficacy of cell-based therapy. This study sought to assess the safety and efficacy of MSCs with MK overexpression transplantation in a rat model of MI. A pLenO-DCE vector lentivirus encoding MK was constructed and infected in MSCs. MSC migration activity and cytoprotection was examined in hypoxia-induced H9C2 cells using transwell insert in vitro. Rats were randomized into five groups: sham, MI plus injection of phosphate buffered saline (PBS), MSCs, MSCs-green fluorescent protein (MSCs-GFP) and MSCs-MK, respectively. Survival rates were compared among groups using log-rank test and left ventricular function was measured by echocardiography at baseline, 4, 8 and 12 weeks. Overexpression of MK partially prevented hypoxia-induced MSC apoptosis and exerted MSC cytoprotection to anoxia induced H9C2 cells. The underlying mechanisms may be associated with the increased mRNA and protein levels of vascular endothelial growth factor (VEGF), transformation growth factor-β (TGF-β), insulin-like growth factor 1 (IGF-1) and stromal cell-derived factor 1 (SDF-1a) in MSCs-MK compared with isolated MSCs and MSCs-GFP. Consistent with the qPCR results, the culture supernatant of MSCs-MK had more SDF-1a (9.23 ng/ml), VEGF (8.34 ng/ml) and TGF-β1 (17.88 ng/ml) expression. In vivo, a greater proportion of cell survival was observed in the MSCs-MK group than in the MSCs-GFP group. Moreover, MSCs-MK administration was related to a significant improvement of cardiac function compared with other control groups at 12 weeks. Therapies employing MSCs with MK overexpression may represent an effective treatment for improving cardiac dysfunction and survival rate after MI.

Mesenchymal stem cells with overexpression of midkine enhance cell survival and attenuate cardiac dysfunction in a rat model of myocardial infarction

PubMed Central

2014-01-01

Introduction Elevated midkine (MK) expression may contribute to ventricular remodeling and ameliorate cardiac dysfunction after myocardial infarction (MI). Ex vivo modification of signaling mechanisms in mesenchymal stem cells (MSCs) with MK overexpression may improve the efficacy of cell-based therapy. This study sought to assess the safety and efficacy of MSCs with MK overexpression transplantation in a rat model of MI. Methods A pLenO-DCE vector lentivirus encoding MK was constructed and infected in MSCs. MSC migration activity and cytoprotection was examined in hypoxia-induced H9C2 cells using transwell insert in vitro. Rats were randomized into five groups: sham, MI plus injection of phosphate buffered saline (PBS), MSCs, MSCs-green fluorescent protein (MSCs-GFP) and MSCs-MK, respectively. Survival rates were compared among groups using log-rank test and left ventricular function was measured by echocardiography at baseline, 4, 8 and 12 weeks. Results Overexpression of MK partially prevented hypoxia-induced MSC apoptosis and exerted MSC cytoprotection to anoxia induced H9C2 cells. The underlying mechanisms may be associated with the increased mRNA and protein levels of vascular endothelial growth factor (VEGF), transformation growth factor-β (TGF-β), insulin-like growth factor 1 (IGF-1) and stromal cell-derived factor 1 (SDF-1a) in MSCs-MK compared with isolated MSCs and MSCs-GFP. Consistent with the qPCR results, the culture supernatant of MSCs-MK had more SDF-1a (9.23 ng/ml), VEGF (8.34 ng/ml) and TGF-β1 (17.88 ng/ml) expression. In vivo, a greater proportion of cell survival was observed in the MSCs-MK group than in the MSCs-GFP group. Moreover, MSCs-MK administration was related to a significant improvement of cardiac function compared with other control groups at 12 weeks. Conclusions Therapies employing MSCs with MK overexpression may represent an effective treatment for improving cardiac dysfunction and survival rate after MI. PMID:24635859

Effect of beam hardening on transmural myocardial perfusion quantification in myocardial CT imaging

NASA Astrophysics Data System (ADS)

Fahmi, Rachid; Eck, Brendan L.; Levi, Jacob; Fares, Anas; Wu, Hao; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

2016-03-01

The detection of subendocardial ischemia exhibiting an abnormal transmural perfusion gradient (TPG) may help identify ischemic conditions due to micro-vascular dysfunction. We evaluated the effect of beam hardening (BH) artifacts on TPG quantification using myocardial CT perfusion (CTP). We used a prototype spectral detector CT scanner (Philips Healthcare) to acquire dynamic myocardial CTP scans in a porcine ischemia model with partial occlusion of the left anterior descending (LAD) coronary artery guided by pressure wire-derived fractional flow reserve (FFR) measurements. Conventional 120 kVp and 70 keV projection-based mono-energetic images were reconstructed from the same projection data and used to compute myocardial blood flow (MBF) using the Johnson-Wilson model. Under moderate LAD occlusion (FFR~0.7), we used three 5 mm short axis slices and divided the myocardium into three LAD segments and three remote segments. For each slice and each segment, we characterized TPG as the mean "endo-to-epi" transmural flow ratio (TFR). BH-induced hypoenhancement on the ischemic anterior wall at 120 kVp resulted in significantly lower mean TFR value as compared to the 70 keV TFR value (0.29+/-0.01 vs. 0.55+/-0.01 p<1e-05). No significant difference was measured between 120 kVp and 70 keV mean TFR values on segments moderately affected or unaffected by BH. In the entire ischemic LAD territory, 120 kVp mean endocardial flow was significantly reduced as compared to mean epicardial flow (15.80+/-10.98 vs. 40.85+/-23.44 ml/min/100g; p<1e-04). At 70 keV, BH was effectively minimized resulting in mean endocardial MBF of 40.85+/-15.3407 ml/min/100g vs. 74.09+/-5.07 ml/min/100g (p=0.0054) in the epicardium. We also found that BH artifact in the conventional 120 kVp images resulted in falsely reduced MBF measurements even under non-ischemic conditions.

Value of speckle tracking echocardiography for detection of clinically silent left ventricular dysfunction in patients with β-thalassemia.

PubMed

Parsaee, Mozhgan; Saedi, Sedigheh; Joghataei, Pegah; Azarkeivan, Azita; Alizadeh Sani, Zahra

2017-10-01

β-Thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia requiring chronic transfusion therapy. Cardiac involvement is the main cause of death in patients with thalassemia major. The narrow border is between overt myocardial dysfunction and clinically silent left ventricular (LV) dysfunction in patients with thalassemia. Therefore, we need novel parameters in different imaging techniques to discover cardiac involvement in an early and subtle stage. We explore to find a novel, straightforward and informative parameter in echocardiography as a noninvasive, economical and really routine in clinical practice. In this prospective study, 55 patients, who are known cases of β-thalassemia major, receiving long-term blood transfusions and undergoing iron chelation therapy were enrolled. Ferritin level, cardiac magnetic resonance (CMR) T2 * value, full conventional echocardiography and speckle tracking, LV regional circumferential and longitudinal strain values (%) and time-to-peak strain (ms) of 17 segments cardiac model in eyeball tomogram were measured. There was a significant reduction in global longitudinal strain (GLS) (-20.9% ± 1.9 vs. -22.2 ± 1.03) and also basal segments longitudinal strain compared to normal subjects group (-17.4% ± 2.7 vs. -19.6% ± 1.2). There was no significant difference in circumferential strain value between thalassemia patients and normal control group. Interestingly, there was no significant correlation between GLS and CMR T2 * values showing no association between cardiac iron load and longitudinal strain. Speckle tracking echocardiography could be used as a feasible method for evaluating subclinical myocardial dysfunction in patients with thalassemia major. Echocardiography, using GLS, could predict clinically silent myocardial dysfunction independent of CMR (T2 * value) and extension of iron deposition. Our study also puts forward other causes such as chronic tissue hypoxia resulting

The Future of Qualitative Research in Psychology: Accentuating the Positive.

PubMed

Gough, Brendan; Lyons, Antonia

2016-06-01

In this paper we reflect on current trends and anticipate future prospects regarding qualitative research in Psychology. We highlight various institutional and disciplinary obstacles to qualitative research diversity, complexity and quality. At the same time, we note some causes for optimism, including publication breakthroughs and vitality within the field. The paper is structured into three main sections which consider: 1) the positioning of qualitative research within Psychology; 2) celebrating the different kinds of knowledge produced by qualitative research; and 3) implementing high quality qualitative research. In general we accentuate the positive, recognising and illustrating innovative qualitative research practices which generate new insights and propel the field forward. We conclude by emphasising the importance of research training: for qualitative research to flourish within Psychology (and beyond), students and early career researchers require more sophisticated, in-depth instruction than is currently offered.

Discrete microstructural cues for the attenuation of fibrosis following myocardial infarction.

PubMed

Pinney, James R; Du, Kim T; Ayala, Perla; Fang, Qizhi; Sievers, Richard E; Chew, Patrick; Delrosario, Lawrence; Lee, Randall J; Desai, Tejal A

2014-10-01

Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. We have developed a therapeutic materials strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructures to mechanically alter the microenvironment. Polymeric microstructures were fabricated using photolithographic techniques and studied in a three-dimensional culture model of the fibrotic environment and by direct injection into the infarct zone of adult rats. Here, we show dose-dependent down-regulation of expression of genes associated with the mechanical fibrotic response in the presence of microstructures. Injection of this microstructured material into the infarct zone decreased levels of collagen and TGF-β, increased elastin deposition and vascularization in the infarcted region, and improved functional outcomes after six weeks. Our results demonstrate the efficacy of these discrete anti-fibrotic microstructures and suggest a potential therapeutic materials approach for combatting pathologic fibrosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chronic Hypoxia Accentuates Dysanaptic Lung Growth.

PubMed

Llapur, Conrado J; Martínez, Myriam R; Grassino, Pedro T; Stok, Ana; Altieri, Héctor H; Bonilla, Federico; Caram, María M; Krowchuk, Natasha M; Kirby, Miranda; Coxson, Harvey O; Tepper, Robert S

2016-08-01

Adults born and raised at high altitudes have larger lung volumes and greater pulmonary diffusion capacity compared with adults at low altitude; however, it remains unclear whether the air and tissue volumes have comparable increases and whether there is a difference in airway size. To assess the effect of chronic hypoxia on lung growth using in vivo high-resolution computed tomography measurements. Healthy adults born and raised at moderate altitude (2,000 m above sea level; n = 19) and at low altitude (400 m above sea level; n = 23) underwent high-resolution computed tomography. Differences in total lung, air, and tissue volume, mean lung density, as well as airway lumen and wall areas in anatomically matched airways were compared between groups. No significant differences for age, sex, weight, or height were found between the two groups (P > 0.05). In a multivariate regression model, altitude was a significant contributor for total lung volume (P = 0.02), air volume (P = 0.03), and tissue volume (P = 0.03), whereby the volumes were greater for the moderate- versus the low-altitude group. However, altitude was not a significant contributor for mean lung density (P = 0.35) or lumen and wall areas in anatomically matched segmental, subsegmental, and subsubsegmental airways. Our findings suggest that the adult lung did not increase lung volume later in life by expansion of an existing number of alveoli, but rather from increased alveolarization early in life. In addition, chronic hypoxia accentuates dysanaptic lung growth by increasing the lung parenchyma but not the airways.

Acute impairment of regional myocardial glucose uptake in the apical ballooning (takotsubo) syndrome.

PubMed

Bybee, Kevin A; Murphy, Joseph; Prasad, Abhiram; Wright, R Scott; Lerman, Amir; Rihal, Charanjit S; Chareonthaitawee, Panithaya

2006-01-01

Apical ballooning syndrome (ABS) is a poorly understood clinical entity characterized by acute, transient systolic dysfunction of the left ventricular (LV) apex in the absence of epicardial coronary artery disease and commonly associated with acute emotional stress. We report abnormal regional myocardial perfusion and glucose uptake in 4 consecutive ABS patients studied using positron emission tomography with 13N-ammonia and 18F-fluorodeoxyglucose within 72 hours of presentation with ABS. All patients were postmenopausal females, 3 of whom had a major recent life stress event. Coronary angiography revealed no or minimal obstructive epicardial coronary artery disease. All patients exhibited reduced glucose uptake in the mid-LV and apical myocardial segments, which was out of proportion to perfusion abnormalities in half of the cases. In all 4 patients, affected regions subsequently recovered regional LV systolic function within 6 weeks.

Characterizing cardiac dysfunction in fetuses with left congenital diaphragmatic hernia.

PubMed

Cruz-Lemini, Mónica; Valenzuela-Alcaraz, Brenda; Granados-Montiel, Julio; Martínez, Josep M; Crispi, Fátima; Gratacós, Eduard; Cruz-Martínez, Rogelio

2018-03-23

To evaluate cardiac function by conventional echocardiography and tissue Doppler imaging in fetuses with left congenital diaphragmatic hernia (CDH). Conventional echocardiography (myocardial performance index, ventricular filling velocities, and E/A ratios) and tissue Doppler imaging (annular myocardial peak velocities, E/E' and E'/A' ratios) in mitral, septal, and tricuspid annulus were evaluated in a cohort of 31 left-sided CDH fetuses and compared with 75 controls matched for gestational age 2:1. In comparison to controls, CDH fetuses had prolonged isovolumetric time periods (isovolumetric contraction time 35 ms vs 28 ms, P < .001), with higher myocardial performance index (0.49 vs 0.42, P < .001) and tricuspid E/A ratios (0.77 vs 0.72, P = .033). Longitudinal function assessed by tissue Doppler showed signs of impaired relaxation (mitral lateral A' 8.0 vs 10.1 cm/s, P < .001 and an increased mitral lateral E'/A' ratio 0.93 vs 0.78, P < .001) in the CDH fetuses as compared with controls, with preserved systolic function. Left CDH fetuses show echocardiographic signs of diastolic dysfunction, probably secondary to fetal heart compression, maintaining a preserved systolic function. © 2018 John Wiley & Sons, Ltd.

True-3D Accentuating of Grids and Streets in Urban Topographic Maps Enhances Human Object Location Memory

PubMed Central

Edler, Dennis; Bestgen, Anne-Kathrin; Kuchinke, Lars; Dickmann, Frank

2015-01-01

Cognitive representations of learned map information are subject to systematic distortion errors. Map elements that divide a map surface into regions, such as content-related linear symbols (e.g. streets, rivers, railway systems) or additional artificial layers (coordinate grids), provide an orientation pattern that can help users to reduce distortions in their mental representations. In recent years, the television industry has started to establish True-3D (autostereoscopic) displays as mass media. These modern displays make it possible to watch dynamic and static images including depth illusions without additional devices, such as 3D glasses. In these images, visual details can be distributed over different positions along the depth axis. Some empirical studies of vision research provided first evidence that 3D stereoscopic content attracts higher attention and is processed faster. So far, the impact of True-3D accentuating has not yet been explored concerning spatial memory tasks and cartography. This paper reports the results of two empirical studies that focus on investigations whether True-3D accentuating of artificial, regular overlaying line features (i.e. grids) and content-related, irregular line features (i.e. highways and main streets) in official urban topographic maps (scale 1/10,000) further improves human object location memory performance. The memory performance is measured as both the percentage of correctly recalled object locations (hit rate) and the mean distances of correctly recalled objects (spatial accuracy). It is shown that the True-3D accentuating of grids (depth offset: 5 cm) significantly enhances the spatial accuracy of recalled map object locations, whereas the True-3D emphasis of streets significantly improves the hit rate of recalled map object locations. These results show the potential of True-3D displays for an improvement of the cognitive representation of learned cartographic information. PMID:25679208

Adverse postresuscitation myocardial effects elicited by buffer-induced alkalemia ameliorated by NHE-1 inhibition in a rat model of ventricular fibrillation.

PubMed

Lamoureux, Lorissa; Radhakrishnan, Jeejabai; Mason, Thomas G; Kraut, Jeffrey A; Gazmuri, Raúl J

2016-11-01

Major myocardial abnormalities occur during cardiac arrest and resuscitation including intracellular acidosis-partly caused by CO 2 accumulation-and activation of the Na + -H + exchanger isoform-1 (NHE-1). We hypothesized that a favorable interaction may result from NHE-1 inhibition during cardiac resuscitation followed by administration of a CO 2 -consuming buffer upon return of spontaneous circulation (ROSC). Ventricular fibrillation was electrically induced in 24 male rats and left untreated for 8 min followed by defibrillation after 8 min of cardiopulmonary resuscitation (CPR). Rats were randomized 1:1:1 to the NHE-1 inhibitor zoniporide or vehicle during CPR and disodium carbonate/sodium bicarbonate buffer or normal saline (30 ml/kg) after ROSC. Survival at 240 min declined from 100% with Zoniporide/Saline to 50% with Zoniporide/Buffer and 25% with Vehicle/Buffer (P = 0.004), explained by worsening postresuscitation myocardial dysfunction. Marked alkalemia occurred after buffer administration along with lactatemia that was maximal after Vehicle/Buffer, attenuated by Zoniporide/Buffer, and minimal with Zoniporide/Saline [13.3 ± 4.8 (SD), 9.2 ± 4.6, and 2.7 ± 1.0 mmol/l; P ≤ 0.001]. We attributed the intense postresuscitation lactatemia to enhanced glycolysis consequent to severe buffer-induced alkalemia transmitted intracellularly by an active NHE-1. We attributed the worsened postresuscitation myocardial dysfunction also to severe alkalemia intensifying Na + entry via NHE-1 with consequent Ca 2+ overload injuring mitochondria, evidenced by increased plasma cytochrome c Both buffer-induced effects were ameliorated by zoniporide. Accordingly, buffer-induced alkalemia after ROSC worsened myocardial function and survival, likely through enhancing NHE-1 activity. Zoniporide attenuated these effects and uncovered a complex postresuscitation acid-base physiology whereby blood pH drives NHE-1 activity and compromises mitochondrial function and integrity along

The heartbreak of depression: 'Psycho-cardiac' coupling in myocardial infarction.

PubMed

Headrick, John P; Peart, Jason N; Budiono, Boris P; Shum, David H K; Neumann, David L; Stapelberg, Nicolas J C

2017-05-01

Ample evidence identifies strong links between major depressive disorder (MDD) and both risk of ischemic or coronary heart disease (CHD) and resultant morbidity and mortality. The molecular mechanistic bases of these linkages are poorly defined. Systemic factors linked to MDD, including vascular dysfunction, atherosclerosis, obesity and diabetes, together with associated behavioral changes, all elevate CHD risk. Nonetheless, experimental evidence indicates the myocardium is also directly modified in depression, independently of these factors, impairing infarct tolerance and cardioprotection. It may be that MDD effectively breaks the heart's intrinsic defense mechanisms. Four extrinsic processes are implicated in this psycho-cardiac coupling, presenting potential targets for therapeutic intervention if causally involved: sympathetic over-activity vs. vagal under-activity, together with hypothalamic-pituitary-adrenal (HPA) axis and immuno-inflammatory dysfunctions. However, direct evidence of their involvement remains limited, and whether targeting these upstream mediators is effective (or practical) in limiting the cardiac consequences of MDD is unknown. Detailing myocardial phenotype in MDD can also inform approaches to cardioprotection, yet cardiac molecular changes are similarly ill defined. Studies support myocardial sensitization to ischemic insult in models of MDD, including worsened oxidative and nitrosative damage, apoptosis (with altered Bcl-2 family expression) and infarction. Moreover, depression may de-sensitize hearts to protective conditioning stimuli. The mechanistic underpinnings of these changes await delineation. Such information not only advances our fundamental understanding of psychological determinants of health, but also better informs management of the cardiac consequences of MDD and implementing cardioprotection in this cohort. Copyright © 2017 Elsevier Ltd. All rights reserved.

Positron Emission Tomography for the Assessment of Myocardial Viability

PubMed Central

2005-01-01

Executive Summary Objective The objective was to update the 2001 systematic review conducted by the Institute For Clinical Evaluative Sciences (ICES) on the use of positron emission tomography (PET) in assessing myocardial viability. The update consisted of a review and analysis of the research evidence published since the 2001 ICES review to determine the effectiveness and cost-effectiveness of PET in detecting left ventricular (LV) viability and predicting patient outcomes after revascularization in comparison with other noninvasive techniques. Background Left Ventricular Viability Heart failure is a complex syndrome that impairs the contractile ability of the heart to maintain adequate blood circulation, resulting in poor functional capacity and increased risk of morbidity and mortality. It is the leading cause of hospitalization in elderly Canadians. In more than two-thirds of cases, heart failure is secondary to coronary heart disease. It has been shown that dysfunctional myocardium resulting from coronary heart disease (CAD) may recover contractile function (i.e. considered viable). Dysfunctional but viable myocardium may have been stunned by a brief episode of ischemia, followed by restoration of perfusion, and may regain function spontaneously. It is believed that repetitive stunning results in hibernating myocardium that will only regain contractile function upon revascularization. For people with CAD and severe LV dysfunction (left ventricular ejection fraction [LVEF] <35%) refractory to medical therapy, coronary artery bypass and heart transplantation are the only treatment options. The opportunity for a heart transplant is limited by scarcityof donor hearts. Coronary artery bypass in these patients is associated with high perioperative complications; however, there is evidence that revascularization in the presence of dysfunctional but viable myocardium is associated with survival benefits and lower rates of cardiac events. The assessment of left

The association of ventricular tachycardia and endothelial dysfunction in the setting of acute myocardial infarction with ST elevation

PubMed Central

Škerk, Vedrana; Markotić, Alemka; Brkljačić, Diana Delić; Manola, Šime; Krčmar, Tomislav; Gabrić, Ivo Darko; Štajminger, Gordana; Pintarić, Hrvoje

2013-01-01

Background Ventricular tachycardia (VT) is frequently seen in ischemic settings like acute myocardial infarction with ST segment elevation (STEMI). Endothelial dysfunction (ED) represents inflammation and the loss of all protective features of the endothelium. We aimed to examine the association between VT and ED in patients with STEMI. Material/Methods The study included 90 subjects (30 with VT and acute STEMI, 30 with STEMI without VT, and 30 controls). Sera of all subjects were tested on ED markers by enzyme immunoassay: sICAM-1 (intracellular adhesive molecule-1), sVCAM-1 (vascular adhesive molecule-1), P- and E-selectins, and VEGF (vascular endothelial growth factor). In addition, CRP (C-reactive protein) was detected. Results Significantly increased values of low-density lipoprotein, triglycerides, leukocytes, creatinine, and the number of cigarettes smoked were observed among patients with VT+STEMI in comparison to controls. The levels of E-selectin were significantly lower in the VT+STEMI group than in the other groups, while the levels of VCAM-1 were significantly higher in the groups with STEMI and VT+STEMI compared to the controls. Lower levels of VEGF were recorded in STEMI and VT+STEMI groups compared to the control group. A significant correlation between CRP and VCAM-1 in patients with VT +STEMI was demonstrated. Conclusions We showed that ED may have a role in the immunopathogenesis of VT in patients with STEMI. The role of sE-selectin and correlation of sVCAM-1 with CRP as possible ED predictive markers in patients with VT+STEMI should be further investigated in a large cohort of patients. PMID:24253420

SIRT1 activation attenuates diastolic dysfunction by reducing cardiac fibrosis in a model of anthracycline cardiomyopathy.

PubMed

Cappetta, Donato; Esposito, Grazia; Piegari, Elena; Russo, Rosa; Ciuffreda, Loreta Pia; Rivellino, Alessia; Berrino, Liberato; Rossi, Francesco; De Angelis, Antonella; Urbanek, Konrad

2016-02-15

Doxorubicin (DOXO) is an effective anti-neoplastic drug but its clinical benefits are hampered by cardiotoxicity. Oxidative stress, apoptosis and myocardial fibrosis mediate the anthracycline cardiomyopathy. ROS trigger TGF-β pathway that activates cardiac fibroblasts promoting fibrosis. Myocardial stiffness contributes to diastolic dysfunction, less studied aspect of anthracycline cardiomyopathy. Considering the role of SIRT1 in the inhibition of the TGF-β/SMAD3 pathway, resveratrol (RES), a SIRT1 activator, might improve cardiac function by interfering with the development of cardiac fibrosis in a model of DOXO-induced cardiomyopathy. F344 rats received a cumulative dose of 15 mg/kg of DOXO in 2 weeks or DOXO+RES (DOXO and RES, 2.5mg/kg/day, concomitantly for 2 weeks and then RES alone for 1 more week). The effects of RES on cardiac fibroblasts were also tested in vitro. Along with systolic dysfunction, DOXO was also responsible of diastolic abnormalities. Myocardial stiffness correlated with fibroblast activation and collagen deposition. DOXO+RES co-treatment significantly improved ± dP/dt and, more interestingly, ameliorated end-diastolic pressure/volume relationship. Treatment with RES resulted in reduced fibrosis and fibroblast activation and, most importantly, the mortality rate was significantly reduced in DOXO+RES group. Fibroblasts isolated from DOXO+RES-treated rats, in which SIRT1 was upregulated, showed decreased levels of TGF-β and pSMAD3/SMAD3 when compared to cells isolated from DOXO-exposed hearts. Our findings reveal a key role of SIRT1 in supporting animal survival and functional parameters of the heart. SIRT1 activation by interfering with fibrogenesis can improve relaxation properties of myocardium and attenuate myocardial remodeling related to chemotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cpg-ODN, a TLR9 Agonist, Aggravates Myocardial Ischemia/Reperfusion Injury by Activation of TLR9-P38 MAPK Signaling.

PubMed

Xie, Liang; He, Songqing; Kong, Na; Zhu, Ying; Tang, Yi; Li, Jianhua; Liu, Zhengbing; Liu, Jing; Gong, Jianbin

2018-06-19

Toll-like receptors (TLRs) have been implicated in myocardial ischemia/ reperfusion (I/R) injury. We examined the effect of CpG-oligodeoxynucleotide (ODN) on myocardial I/R injury. Male Sprague-Dawley rats were treated with either CpG-ODN or control ODN 1 h prior to myocardial ischemia (30 min) followed by reperfusion. Rats treated with phosphate-buffered saline (PBS) served as I/R controls (n = 8/group). Infarct size was determined by 2,3,5-triphenyltetrazolium chloride and Evans blue straining. Cardiac function was examined by echocardiography before and up to 14 days after myocardial I/R. CpG-ODN administration significantly increased infarct size and reduced cardiac function and survival rate after myocardial I/R, compared to the PBS-treated I/R group. Control-ODN did not alter I/R-induced myocardial infarct size, cardiac dysfunction, and survival rate. Additionally, CpG-ODN promoted I/R-induced myocardial apoptosis and cleaved caspase-3 levels in the myocardium. CpG-ODN increased TLR9 activation and p38 phosphorylation in the myocardium. In vitro data also suggested that CpG-ODN treatment induced TLR9 activation and p38 phosphorylation. Importantly, p38 mitogen-activated protein kinase (MAPK) inhibition abolished CpG-ODN-induced cardiac injury. CpG-ODN, the TLR9 ligand, accelerates myocardial I/R injury. The mechanisms involve activation of the TLR9-p38 MAPK signaling pathway. © 2018 The Author(s). Published by S. Karger AG, Basel.

Tissue Inhibitor of Matrix Metalloproteinase-1 Promotes Myocardial Fibrosis by Mediating CD63-Integrin β1 Interaction.

PubMed

Takawale, Abhijit; Zhang, Pu; Patel, Vaibhav B; Wang, Xiuhua; Oudit, Gavin; Kassiri, Zamaneh

2017-06-01

Myocardial fibrosis is excess accumulation of the extracellular matrix fibrillar collagens. Fibrosis is a key feature of various cardiomyopathies and compromises cardiac systolic and diastolic performance. TIMP1 (tissue inhibitor of metalloproteinase-1) is consistently upregulated in myocardial fibrosis and is used as a marker of fibrosis. However, it remains to be determined whether TIMP1 promotes tissue fibrosis by inhibiting extracellular matrix degradation by matrix metalloproteinases or via an matrix metalloproteinase-independent pathway. We examined the function of TIMP1 in myocardial fibrosis using Timp1 -deficient mice and 2 in vivo models of myocardial fibrosis (angiotensin II infusion and cardiac pressure overload), in vitro analysis of adult cardiac fibroblasts, and fibrotic myocardium from patients with dilated cardiomyopathy (DCM). Timp1 deficiency significantly reduced myocardial fibrosis in both in vivo models of cardiomyopathy. We identified a novel mechanism for TIMP1 action whereby, independent from its matrix metalloproteinase-inhibitory function, it mediates an association between CD63 (cell surface receptor for TIMP1) and integrin β1 on cardiac fibroblasts, initiates activation and nuclear translocation of Smad2/3 and β-catenin, leading to de novo collagen synthesis. This mechanism was consistently observed in vivo, in cultured cardiac fibroblasts, and in human fibrotic myocardium. In addition, after long-term pressure overload, Timp1 deficiency persistently reduced myocardial fibrosis and ameliorated diastolic dysfunction. This study defines a novel matrix metalloproteinase-independent function of TIMP1 in promoting myocardial fibrosis. As such targeting TIMP1 could prove to be a valuable approach in developing antifibrosis therapies. © 2017 American Heart Association, Inc.

Profound bioenergetic abnormalities in peri-infarct myocardial regions.

PubMed

Hu, Qingsong; Wang, Xiaohong; Lee, Joseph; Mansoor, Abdul; Liu, Jingbo; Zeng, Lepeng; Swingen, Cory; Zhang, Ge; Feygin, Julia; Ochiai, Koichi; Bransford, Toni L; From, Arthur H L; Bache, Robert J; Zhang, Jianyi

2006-08-01

Regions of myocardial infarct (MI) are surrounded by a border zone (BZ) of normally perfused but dysfunctional myocardium. Although systolic dysfunction has been attributed to elevated wall stress in this region, there is evidence that intrinsic abnormalities of contractile performance exist in BZ myocardium. This study examined whether decreases of high-energy phosphates (HEP) and mitochondrial F(1)F(0)-ATPase (mtATPase) subunits typical of failing myocardium exist in BZ myocardium of compensated postinfarct remodeled hearts. Eight pigs were studied 6 wk after MI was produced by ligation of the left anterior descending coronary artery (LAD) distal to the second diagonal. Animals developed compensated LV remodeling with a decrease of ejection fraction from 54.6 +/- 5.4% to 31 +/- 2.1% (MRI) 5 wk after LAD occlusion. The remote zone (RZ) myocardium demonstrated modest decreases of ATP and mtATPase components. In contrast, BZ myocardium demonstrated profound abnormalities with ATP levels decreased to 42% of normal, and phosphocreatine-to-ATP ratio ((31)P-magnetic resonance spectroscopy) decreased from 2.06 +/- 0.19 in normal hearts to 1.07 +/- 0.10, with decreases in alpha-, beta-, OSCP, and IF(1) subunits of mtATPase, especially in the subendocardium. The reduction of myocardial creatine kinase isoform protein expression was also more severe in the BZ relative to the RZ myocardium. These abnormalities were independent of a change in mitochondrial content because the mitochondrial citrate synthase protein level was not different between the BZ and RZ. This regional heterogeneity of ATP content and expression of key enzymes in ATP production suggests that energetic insufficiency in the peri-infarct region may contribute to the transition from compensated LV remodeling to congestive heart failure.

Treatment of Angina and Microvascular Coronary Dysfunction

PubMed Central

Samim, Arang; Nugent, Lynn; Mehta, Puja K.; Shufelt, Chrisandra; Merz, C. Noel Bairey

2014-01-01

Opinion statement Microvascular coronary dysfunction (MCD) is an increasingly recognized cause of cardiac ischemia and angina, more commonly diagnosed in women. Patients with MCD present with the triad of persistent chest pain, ischemic changes on stress testing, and no obstructive coronary artery disease (CAD) on cardiac catheterization. Data from National Heart, Lung and Blood Institute (NHLBI)-sponsored Women’s Ischemia Syndrome Evaluation (WISE) study has shown that the diagnosis of MCD is not benign, with a 2.5% annual risk of adverse cardiac events including myocardial infarction, stroke, congestive heart failure, or death. The gold standard diagnostic test for MCD is an invasive coronary reactivity test (CRT), which uses acetylcholine, adenosine, and nitroglycerin to test the endothelial dependent and independent, microvascular and macrovascular coronary function. The CRT allows for diagnostic and treatment options as well as further risk stratifying patients for future cardiovascular events. Treatment of angina and MCD should be aimed at ischemia disease management to reduce risk of adverse cardiac events, ameliorating symptoms to improve quality of life, and to decrease the morbidity from unnecessary and repeated cardiac catheterization in patients with open coronary arteries. A comprehensive treatment approach aimed at risk factor managment, including lifestyle counseling regarding smoking cessation, nutrition and physical activity should be initiated. Current pharmacotherapy for MCD can include the treatment of microvascular endothelial dysfunction (statins, angiotensin-converting enzyme inhibitor, low dose aspirin), as well as treatment for angina and myocardial ischemia (beta blockers, calcium channel blockers, nitrates, ranolazine). Additional symptom management techniques can include tri-cyclic medication, enhanced external counterpulsation, autogenic training, and spinal cord stimulation. While our current therapies are effective in the treatment

Usefulness of Speckle-Tracking Imaging for Right Ventricular Assessment after Acute Myocardial Infarction: A Magnetic Resonance Imaging/Echocardiographic Comparison within the Relation between Aldosterone and Cardiac Remodeling after Myocardial Infarction Study.

PubMed

Lemarié, Jérémie; Huttin, Olivier; Girerd, Nicolas; Mandry, Damien; Juillière, Yves; Moulin, Frédéric; Lemoine, Simon; Beaumont, Marine; Marie, Pierre-Yves; Selton-Suty, Christine

2015-07-01

Right ventricular (RV) dysfunction after acute myocardial infarction (AMI) is frequent and associated with poor prognosis. The complex anatomy of the right ventricle makes its echocardiographic assessment challenging. Quantification of RV deformation by speckle-tracking echocardiography is a widely available and reproducible technique that readily provides an integrated analysis of all segments of the right ventricle. The aim of this study was to investigate the accuracy of conventional echocardiographic parameters and speckle-tracking echocardiographic strain parameters in assessing RV function after AMI, in comparison with cardiac magnetic resonance imaging (CMR). A total of 135 patients admitted for AMI (73 anterior, 62 inferior) were prospectively studied. Right ventricular function was assessed by echocardiography and CMR within 2 to 4 days of hospital admission. Right ventricular dysfunction was defined as CMR RV ejection fraction < 50%. Right ventricular global peak longitudinal systolic strain (GLPSS) was calculated by averaging the strain values of the septal, lateral, and inferior walls. Right ventricular dysfunction was documented in 20 patients. Right ventricular GLPSS was the best echographic correlate of CMR RV ejection fraction (r = -0.459, P < .0001) and possessed good diagnostic value for RV dysfunction (area under the receiver operating characteristic curve [AUROC], 0.724; 95% CI, 0.590-0.857), which was comparable with that of RV fractional area change (AUROC, 0.756; 95% CI, 0.647-0.866). In patients with inferior myocardial infarctions, the AUROCs for RV GLPSS (0.822) and inferolateral strain (0.877) were greater than that observed for RV fractional area change (0.760) Other conventional echocardiographic parameters performed poorly (all AUROCs < 0.700). After AMI, RV GLPSS is the best correlate of CMR RV ejection fraction. In patients with inferior AMIs, RV GLPSS displays even higher diagnostic value than conventional echocardiographic

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.

Mechanisms of load dependency of myocardial ischemia reperfusion injury

PubMed Central

Mozaffari, Mahmood S; Liu, Jun Yao; Abebe, Worku; Baban, Babak

2013-01-01

Coronary artery disease and associated ischemic heart disease are prevalent disorders worldwide. Further, systemic hypertension is common and markedly increases the risk for heart disease. A common denominator of systemic hypertension of various etiologies is increased myocardial load/mechanical stress. Thus, it is likely that high pressure/mechanical stress attenuates the contribution of cardioprotective but accentuates the contribution of cardiotoxic pathways thereby exacerbating the outcome of an ischemia reperfusion insult to the heart. Critical events which contribute to cardiomyocyte injury in the ischemic-reperfused heart include cellular calcium overload and generation of reactive oxygen/nitrogen species which, in turn, promote the opening of the mitochondrial permeability transition pore, an important event in cell death. Increasing evidence also indicates that the myocardium is capable of mounting a robust inflammatory response which contributes importantly to tissue injury. On the other hand, cardioprotective maneuvers of ischemic preconditioning and postconditioning have led to identification of complex web of signaling pathways (e.g., reperfusion injury salvage kinase) which ultimately converge on the mitochondria to exert cytoprotection. The present review is intended to briefly describe mechanisms of cardiac ischemia reperfusion injury followed by a discussion of our work focused on how pressure/mechanical stress modulates endogenous cardiotoxic and cardioprotective mechanisms to ultimately exacerbate ischemia reperfusion injury. PMID:24224132

A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA)

PubMed Central

Porter, John B.; Piga, Antonio; Lai, Yongrong; El-Beshlawy, Amal; Belhoul, Khawla M.; Elalfy, Mohsen; Yesilipek, Akif; Kilinç, Yurdanur; Lawniczek, Tomasz; Habr, Dany; Weisskopf, Marianne; Zhang, Yiyun; Aydinok, Yesim

2014-01-01

Randomized comparison data on the efficacy and safety of deferasirox for myocardial iron removal in transfusion dependent patients are lacking. CORDELIA was a prospective, randomized comparison of deferasirox (target dose 40 mg/kg per day) vs subcutaneous deferoxamine (50-60 mg/kg per day for 5-7 days/week) for myocardial iron removal in 197 β-thalassemia major patients with myocardial siderosis (T2* 6-20 milliseconds) and no signs of cardiac dysfunction (mean age, 19.8 years). Primary objective was to demonstrate noninferiority of deferasirox for myocardial iron removal, assessed by changes in myocardial T2* after 1 year using a per-protocol analysis. Geometric mean (Gmean) myocardial T2* improved with deferasirox from 11.2 milliseconds at baseline to 12.6 milliseconds at 1 year (Gmeans ratio, 1.12) and with deferoxamine (11.6 milliseconds to 12.3 milliseconds; Gmeans ratio, 1.07). The between-arm Gmeans ratio was 1.056 (95% confidence interval [CI], 0.998, 1.133). The lower 95% CI boundary was greater than the prespecified margin of 0.9, establishing noninferiority of deferasirox vs deferoxamine (P = .057 for superiority of deferasirox). Left ventricular ejection fraction remained stable in both arms. Frequency of drug-related adverse events was comparable between deferasirox (35.4%) and deferoxamine (30.8%). CORDELIA demonstrated the noninferiority of deferasirox compared with deferoxamine for myocardial iron removal. This trial is registered at www.clinicaltrials.gov as #NCT00600938. PMID:24385534

Alcohol consumption and accentuated personality traits among young adults in Romania: a cross-sectional study.

PubMed

Rada, Cornelia; Ispas, Alexandru Teodor

2016-10-27

Alcohol consumption (AC) has negative social and economic consequences, affects health, and can create dependence. As dependence is particularly difficult to cure, prevention is important. This study aimed to identify the frequency, quantity, occasions, reasons, type of AC, and correlation with accentuated personality traits among young adults in Romania. Participants were 1359 young adults aged 18-30 years (average age, 22.67 years; standard deviation [SD], 3.02 years) from urban environments including the main university centers. Several questionnaires covering issues such as health risk behavior (smoking, alcohol abuse, unprotected sex, sedentary lifestyles, unhealthy eating), aggression, personality, adaptability, cohesion, and communication were administered to participants between 2013 and 2014. Pearson's chi-square tests and z-tests were used for the analyses. Common reasons young adults first tried AC were curiosity (67.8 %), to be like peers (17.9 %), and adult influence (6.5 %). In terms of AC frequency, 72.5 % consumed alcohol only on special occasions/holidays, 19.4 % on weekends, 4.8 % three to four times per week, and 0.4 % on a daily basis. To overcome sexual/emotional inhibitions or for courage, 2.1 % of participants drank frequently and 23.5 % drank from time to time. AC most often occurred with a group of friends (62.3 %). For 9.7 % of participants, AC was a reason for poor concentration, or problems at work/school. At the time of interview, participants had consumed an average of 319.48 ml beer (SD, 1223.02 ml), 82.75 ml wine (SD, 385.39 ml) and 25.62 ml spirits (SD, 131.34 ml) in the previous week. AC was significantly higher in males (p < 0.01), and in participants aged 23-30 years (p < 0.05). AC was influenced by six accentuated personality traits: Demonstrativeness, Hyper-perseverance, Uncontrollability, Hyperthymia, Cyclothymia, and Exaltation (p < 0.01). AC was relatively high, especially among young men, peer

Myocardial infarction caused by myocardial bridging in a male adolescent athlete.

PubMed

Zhu, Cheng-Gang; Liu, Jun; Liu, Wei-Dong; Xu, Yan-Lu; Wu, Na-Qiong; Guo, Yuan-Lin; Tang, Yi-Da; Jiang, Li-Xin; Li, Jian-Jun

2012-02-01

Myocardial bridging is a common congenital abnormality of a coronary artery, and is usually thought to be a benign anatomical variant. Although rare, previous studies have reported that patients with myocardial bridging may suffer from myocardial ischemia, myocardial infarction (MI), arrhythmias and even sudden death. Here we report the case of an 18-year-old adolescent athlete with myocardial bridging resulting in MI. Coronary angiography revealed 80% luminal narrowing by systolic compression in the proximal and mid segments of the left anterior descending coronary artery, which returned to normal during diastole. We considered that heavy sports might be a potential trigger for his MI attack. Therefore, special attention should be paid to this kind of athlete, especially if adolescent.

Protective effect of N-acetylcysteine activated carbon release microcapsule on myocardial ischemia-reperfusion injury in rats

PubMed Central

Cai, Zhaobin; Shi, Tingting; Zhuang, Rangxiao; Fang, Hongying; Jiang, Xiaojie; Shao, Yidan; Zhou, Hongping

2018-01-01

With the development of science and technology, and development of artery bypass, methods such as cardiopulmonary cerebral resuscitation have been practiced in recent years. Despite this, some methods fail to promote or recover the function of tissues and organs, and in some cases, may aggravate dysfunction and structural damage to tissues. The latter is typical of ischemia-reperfusion (IR) injury. Lipid peroxidation mediated by free radicals is an important process of myocardial IR injury. Myocardial IR has been demonstrated to induce the formation of large numbers of free radicals in rats, which promotes the peroxidation of lipids within unsaturated fatty acids in the myocardial cell membrane. Markers of lipid peroxidation include malondialdehyde, superoxide dismutase and lactic dehydrogenase. Recent studies have demonstrated that N-acetylcysteine (NAC) is able to dilate blood vessels, prevent oxidative damage, improve immunity, inhibit apoptosis and the inflammatory response and promote glutathione synthesis in cells. NAC also improves the systolic function of myocardial cells and cardiac function, prevents myocardial apoptosis, protects ventricular remodeling and vascular remodeling, reduces opiomelanocortin levels in the serum and increases the content of nitric oxide in the serum, thus improving vascular endothelial function. Therefore, NAC has potent pharmacological activity; however, the relatively fast metabolism of NAC, along with its large clinical dose and low bioavailability, limit its applications. The present study combined NAC with medicinal activated carbons, and prepared N-acetylcysteine activated carbon sustained-release microcapsules (ACNACs) to overcome the limitations of NAC. It was demonstrated that ACNACs exerted greater effective protective effects than NAC alone on myocardial IR injury in rats. PMID:29434769

Cardiomyocyte Ogt limits ventricular dysfunction in mice following pressure overload without affecting hypertrophy.

PubMed

Dassanayaka, Sujith; Brainard, Robert E; Watson, Lewis J; Long, Bethany W; Brittian, Kenneth R; DeMartino, Angelica M; Aird, Allison L; Gumpert, Anna M; Audam, Timothy N; Kilfoil, Peter J; Muthusamy, Senthilkumar; Hamid, Tariq; Prabhu, Sumanth D; Jones, Steven P

2017-05-01

The myocardial response to pressure overload involves coordination of multiple transcriptional, posttranscriptional, and metabolic cues. The previous studies show that one such metabolic cue, O-GlcNAc, is elevated in the pressure-overloaded heart, and the increase in O-GlcNAcylation is required for cardiomyocyte hypertrophy in vitro. Yet, it is not clear whether and how O-GlcNAcylation participates in the hypertrophic response in vivo. Here, we addressed this question using patient samples and a preclinical model of heart failure. Protein O-GlcNAcylation levels were increased in myocardial tissue from heart failure patients compared with normal patients. To test the role of OGT in the heart, we subjected cardiomyocyte-specific, inducibly deficient Ogt (i-cmOgt -/- ) mice and Ogt competent littermate wild-type (WT) mice to transverse aortic constriction. Deletion of cardiomyocyte Ogt significantly decreased O-GlcNAcylation and exacerbated ventricular dysfunction, without producing widespread changes in metabolic transcripts. Although some changes in hypertrophic and fibrotic signaling were noted, there were no histological differences in hypertrophy or fibrosis. We next determined whether significant differences were present in i-cmOgt -/- cardiomyocytes from surgically naïve mice. Interestingly, markers of cardiomyocyte dedifferentiation were elevated in Ogt-deficient cardiomyocytes. Although no significant differences in cardiac dysfunction were apparent after recombination, it is possible that such changes in dedifferentiation markers could reflect a larger phenotypic shift within the Ogt-deficient cardiomyocytes. We conclude that cardiomyocyte Ogt is not required for cardiomyocyte hypertrophy in vivo; however, loss of Ogt may exert subtle phenotypic differences in cardiomyocytes that sensitize the heart to pressure overload-induced ventricular dysfunction.

Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

NASA Astrophysics Data System (ADS)

Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

Quantification and significance of diffuse myocardial fibrosis and diastolic dysfunction in childhood hypertrophic cardiomyopathy.

PubMed

Hussain, Tarique; Dragulescu, Andreea; Benson, Lee; Yoo, Shi-Joon; Meng, Howard; Windram, Jonathan; Wong, Derek; Greiser, Andreas; Friedberg, Mark; Mertens, Luc; Seed, Michael; Redington, Andrew; Grosse-Wortmann, Lars

2015-06-01

The purpose of this study was to evaluate the presence of diffuse myocardial fibrosis in children and adolescents with hypertrophic cardiomyopathy (HCM) and to assess associations with echocardiographic and clinical parameters of disease. While a common end point in adults with HCM, it is unclear whether diffuse myocardial fibrosis occurs early in the disease. Cardiac magnetic resonance (CMR) estimation of myocardial post-contrast longitudinal relaxation time (T1) is an increasingly used method to estimate diffuse fibrosis. T1 measurements were taken using standard multi-breath-hold spoiled gradient echo phase-sensitive inversion-recovery CMR before and 15 min after the injection of gadolinium. The tissue-blood partition coefficient was calculated as a function of the ratio of T1 change of myocardium compared with blood. An echocardiogram and blood brain natriuretic peptide (BNP) levels were obtained on the day of the CMR. Twelve controls (mean age 12.8 years; 7 male) and 28 patients with HCM (mean age 12.8 years; 21 male) participated. The partition coefficient for both septal (0.27 ± 0.17 vs. 0.13 ± 0.09; p = 0.03) and lateral walls (0.22 ± 0.09 vs. 0.07 ± 0.10; p < 0.001) was increased in patients compared with controls. Eight patients had overt areas of late gadolinium enhancement (LGE). These patients did not show increased partition coefficient compared with those without LGE (0.27 ± 0.15 vs. 0.27 ± 0.19 and 0.22 ± 0.09 vs. 0.22 ± 0.09; p = 0.95 and 0.98, respectively). However, patients who were symptomatic (dyspnea, arrhythmia and/or chest pain) had higher lateral wall partition coefficient than asymptomatic HCM patients (0.27 ± 0.08 vs. 0.17 ± 0.08; p = 0.006). Similarly, patients with raised BNP (>100 pg/ml) had raised lateral wall coefficients (0.27 ± 0.07 vs. 0.20 ± 0.07; p = 0.03), as did those with traditional risk factors for sudden death (0.27 ± 0.06 vs. 0.18 ± 0.08; p = 0.007). Diffuse fibrosis, measured by the partition coefficient

[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.

Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction.

PubMed

Mohammed, Selma F; Hussain, Saad; Mirzoyev, Sultan A; Edwards, William D; Maleszewski, Joseph J; Redfield, Margaret M

2015-02-10

Characterization of myocardial structural changes in heart failure with preserved ejection fraction (HFpEF) has been hindered by the limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction, and myocardial fibrosis may contribute to HFpEF pathophysiology. We identified HFpEF patients (n=124) and age-appropriate control subjects (noncardiac death, no heart failure diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. With the use of whole-field digital microscopy and automated analysis algorithms in full-thickness left ventricular sections, microvascular density (MVD), myocardial fibrosis, and their relationship were quantified. Subjects with HFpEF had heavier hearts (median, 538 g; 169% of age-, sex-, and body size-expected heart weight versus 335 g; 112% in controls), more severe CAD (65% with ≥1 vessel with >50% diameter stenosis in HFpEF versus 13% in controls), more left ventricular fibrosis (median % area fibrosis, 9.6 versus 7.1) and lower MVD (median 961 versus 1316 vessels/mm(2)) than control (P<0.0001 for all). Myocardial fibrosis increased with decreasing MVD in controls (r=-0.28, P=0.004) and HFpEF (r=-0.26, P=0.004). Adjusting for MVD attenuated the group differences in fibrosis. Heart weight, fibrosis, and MVD were similar in HFpEF patients with CAD versus without CAD. In this study, patients with HFpEF had more cardiac hypertrophy, epicardial CAD, coronary microvascular rarefaction, and myocardial fibrosis than controls. Each of these findings may contribute to the left ventricular diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF. © 2014 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

The Psycho-cardiac Coupling, Myocardial Remodeling, and Neuroendocrine Factor Levels: The Psychosomatics of Major Depressive Disorder.

PubMed

Syeda, Javeria N; Rutkofsky, Ian H; Muhammad, Adnan S; Balla Abdalla, Tarig H; Saghir, Zahid

2018-04-11

The association of major depressive disorder (MDD) with myocardial infarction (MI) and vice versa is not unknown. Depression, along with many other systemic factors like atherosclerosis, obesity, diabetes and vascular dysfunction, contributes to the development of adverse cardiac events in the future and, has always been a topic of interest in the fields of cardiology and psychosomatics. We wrote this review article to elaborate this relationship in detail. This article suggests that the individuals with type D personality who already had cardiovascular disease had undergone more serious myocardial damage. In addition, we elucidated the effects of depression on sympathetic activity and remodeling of myocardium after MI. The alterations in the neuroendocrine factors, which included the changes in levels of Serotonin (5-HT), Norepinephrine and Corticosterone, also geared towards the changes associated with depression-induced myocardial injury. However, we need more studies in the near future to further dig into this association process. Therefore, we recommend more research to explore the relationship of psychological factors and adverse cardiac outcomes.

Periodontitis and myocardial hypertrophy.

PubMed

Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

2017-04-01

There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

Added clinical value of applying myocardial deformation imaging to assess right ventricular function.

PubMed

Sokalskis, Vladislavs; Peluso, Diletta; Jagodzinski, Annika; Sinning, Christoph

2017-06-01

Right heart dysfunction has been found to be a strong prognostic factor predicting adverse outcome in various cardiopulmonary diseases. Conventional echocardiographic measurements can be limited by geometrical assumptions and impaired reproducibility. Speckle tracking-derived strain provides a robust quantification of right ventricular function. It explicitly evaluates myocardial deformation, as opposed to tissue Doppler-derived strain, which is computed from tissue velocity gradients. Right ventricular longitudinal strain provides a sensitive tool for detecting right ventricular dysfunction, even at subclinical levels. Moreover, the longitudinal strain can be applied for prognostic stratification of patients with pulmonary hypertension, pulmonary embolism, and congestive heart failure. Speckle tracking-derived right atrial strain, right ventricular longitudinal strain-derived mechanical dyssynchrony, and three-dimensional echocardiography-derived strain are emerging imaging parameters and methods. Their application in research is paving the way for their clinical use. © 2017, Wiley Periodicals, Inc.

Evaluation of Left Ventricular Diastolic Dysfunction with Early Systolic Dysfunction Using Two-Dimensional Speckle Tracking Echocardiography in Canine Heart Failure Model.

PubMed

Wu, Wei-Chun; Ma, Hong; Xie, Rong-Ai; Gao, Li-Jian; Tang, Yue; Wang, Hao

2016-04-01

This study evaluated the role of two-dimensional speckle tracking echocardiography (2DSTE) for predicting left ventricular (LV) diastolic dysfunction in pacing-induced canine heart failure. Pacing systems were implanted in 8 adult mongrel dogs, and continuous rapid right ventricular pacing (RVP, 240 beats/min) was maintained for 2 weeks. The obtained measurements from 2DSTE included global strain rate during early diastole (SRe) and during late diastole (SRa) in the longitudinal (L-SRe, L-SRa), circumferential (C-SRe, C-SRa), and radial directions (R-SRe, R-SRa). Changes in heart morphology were observed by light microscopy and transmission electron microscopy at 2 weeks. The onset of LV diastolic dysfunction with early systolic dysfunction occurred 3 days after RVP initiation. Most of the strain rate imaging indices were altered at 1 or 3 days after RVP onset and continued to worsen until heart failure developed. Light and transmission electron microscopy showed myocardial vacuolar degeneration and mitochondrial swelling in the left ventricular at 2 weeks after RVP onset. Pearson's correlation analysis revealed that parameters of conventional echocardiography and 2DSTE showed moderate correlation with LV pressure parameters, including E/Esep' (r = 0.58, P < 0.01), L-SRe (r = -0.58, P < 0.01), E/L-SRe (r = 0.65, P < 0.01), and R-SRe (r = 0.53, P < 0.01). ROC curves analysis showed that these indices of conventional echocardiography and strain rate imaging could effectively predict LV diastolic dysfunction (area under the curve: E/Esep' 0.78; L-SRe 0.84; E/L-SRe 0.80; R-SRe 0.80). 2DSTE was a sensitive and accurate technique that could be used for predicting LV diastolic dysfunction in canine heart failure model. © 2015, Wiley Periodicals, Inc.

Elevation of serum N-terminal pro-brain natriuretic peptide after exercise is an index of myocardial damage or a cytoprotective reflection?

PubMed

Faviou, E; Zachari, A; Nounopoulos, C; Agrafiotis, E; Vourli, G; Dionyssiou-Asteriou, A

2008-03-01

Recent investigations have suggested the occurrence of transient cardiac dysfunction and reversible myocardial injury in healthy individuals after heavy exercise. Our purpose was to examine if the release of N-terminal pro-brain natriuretic peptide (NT-proBNP) after intense exercise in obviously healthy participants may have cytoprotective and growth-regulating effects or may result from myocardial dysfunction/damage with changes in cTnT as a marker for myocardial cell necrosis during exercise. In 43 highly-trained male athletes <35 years old, who were examined immediately after exercising as well as 2 days later, 21 age-matched male patients classified as stage-B according to ACC/AHA guidelines and 35 healthy age-matched males, we evaluated NT-proBNP and 3rd generation's cTnT by electrochemiluminescence immunoassay. All participants underwent a detailed cardiac protocol including echocardiography and electrocardiogram (ECG). In athletes, cTnT consistently remained <0.01 mg/L after exercising as well as after 2 days. NTproBNP immediately after exercising was 58.27+/-19.48 ng/L, without reaching pathological levels, decreasing 2 days later to 22.93+/-10.22 ng/L. Our patients maintained high levels of NTproBNP, as much as a six-fold increase with reference to the levels of our study's control group and with cTnT <0.01 mg/L. In the control group, cTnT and NTproBNP levels were statistically similar with those of the athletes 2 days after exercising. NT-proBNP as a biological marker can reliably discriminate pathological from physiological cardiac hypertrophy. A normal plasma concentration of NT-proBNP in consecutive routine check-up, before and after exercise, could minimize the possibility of cardiac dysfunction, whereas persistent elevated plasma concentrations warrant further cardiological evaluation.

Cardiovascular dysfunction in symptomatic primary hyperparathyroidism and its reversal after curative parathyroidectomy: results of a prospective case control study.

PubMed

Agarwal, Gaurav; Nanda, Gitika; Kapoor, Aditya; Singh, Kul Ranjan; Chand, Gyan; Mishra, Anjali; Agarwal, Amit; Verma, Ashok K; Mishra, Saroj K; Syal, Sanjeev K

2013-12-01

Cardiovascular mortality in primary hyperparathyroidism (PHPT) is attributed to myocardial and endothelial dysfunction. In this prospective, case-control study we assessed cardiovascular dysfunction in patients with symptomatic PHPT and its reversal after successful parathyroidectomy. Fifty-six patients with symptomatic PHPT underwent two-dimensional echocardiography, tissue Doppler (diastolic function assessment), serum N-terminal pro-brain natriuretic peptide (s-NTproBNP, a myocardial damage marker), and endothelial- and smooth muscle-dependent vasodilatory response (vascular dysfunction) studies before, 3, and 6 months after parathyroidectomy; 25 age-matched controls were studied similarly. Patients had greater left ventricular mass (192 ± 70 vs. 149 ± 44 g; P = .006), interventricular septal thickness (10.8 ± 2.5 vs. 9.0 ± 1.6 mm; P = .001), posterior wall thickness (9.9 ± 2.0 vs. 8.6 ± 2.2 mm; P = .004), and diastolic dysfunction (lower E/A trans-mitral flow velocity ratio [1.0 ± 0.4 vs. 1.3 ± 0.4; P = .01). Patients had greater s-NTproBNP (4,625 ± 1,130 vs. 58 ± 49 pg/mL; P = .002) and lower endothelial-mediated vasodilation (9.3 ± 8.6 vs. 11.7 ± 6.3%; P = .03) and smooth muscle-mediated vasodilation (20.1 ± 17.9 vs. 23.8 ± 11.2%; P = .01). Improvements in left ventricular mass, systolic and diastolic function, and smooth muscle-mediated vasodilation were noted from 3 to 6 months after parathyroidectomy. Endothelial-mediated vasodilation did not improve significantly. S-NTproBNP levels mirrored echocardiographic changes with a substantial, sustained decrease. Results were similar in hypertensive and normotensive patients. Symptomatic PHPT patients have substantial cardiac and vascular dysfunction, which improve by 6 months after parathyroidectomy. Objective cardiovascular evaluation may improve outcomes in symptomatic PHPT patients. Copyright © 2013 Mosby, Inc. All rights reserved.

Impact of a pure reduction in heart rate for the treatment of left ventricular dysfunction: clinical benefits of ivabradine in the BEAUTIFUL trial.

PubMed

Danchin, Nicolas

2009-01-01

Ivabradine is an I(f) current inhibitor, that has documented antianginal efficacy. The BEAUTIFUL trial tested ivabradine against placebo in a large population of 10,917 patients in sinus rhythm, with coronary artery disease and left ventricular dysfunction, defined as left ventricular ejection fraction < or =35%. Overall, there was no impact of ivabradine on the primary end-point of the trial (cardiovascular mortality, hospitalisation for myocardial infarction, new onset or worsening heart failure). In the placebo arm of the trial, baseline heart rate > or = 70 bpm was associated with an increased risk of cardiovascular mortality, myocardial infarction, heart failure and coronary revascularisation. In the subgroup of patients with a baseline heart rate > or =70 bpm, treatment with ivabradine resulted in a significant, 36% reduction in the risk of myocardial infarction and a 20% reduction in the need for coronary revascularisation. Ivabradine was well tolerated, with an increased rate of treatment discontinuation, mainly due to bradycardia, compared with placebo. Because of its safety and efficacy to control angina, ivabradine should be considered first-line antianginal treatment in coronary artery disease patients with left ventricular dysfunction and increased heart rate, already receiving beta-blocker therapy or in whom these medications are not tolerated.

Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after reversal of hypertension in porcine renovascular disease.

PubMed

Eirin, Alfonso; Zhu, Xiang-Yang; Ferguson, Christopher M; Riester, Scott M; van Wijnen, Andre J; Lerman, Amir; Lerman, Lilach O

2015-01-19

Percutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH). Mesenchymal stem cells (MSCs) restore renal function, but their potential for attenuating cardiac injury after reversal of RVH has not been explored. We hypothesized that replenishment of MSCs during PTRA would improve cardiac function and oxygenation, and decrease myocardial injury in porcine RVH. Pigs were studied after 16 weeks of RVH, RVH treated 4 weeks earlier with PTRA with or without adjunct intra-renal delivery of MSC (10^6 cells), and controls. Cardiac structure, function (fast-computed tomography (CT)), and myocardial oxygenation (Blood-Oxygen-Level-Dependent- magnetic resonance imaging) were assessed in-vivo. Myocardial microvascular density (micro-CT) and myocardial injury were evaluated ex-vivo. Kidney venous and systemic blood levels of inflammatory markers were measured and their renal release calculated. PTRA normalized blood pressure, yet stenotic-kidney glomerular filtration rate, similarly blunted in RVH and RVH + PTRA, normalized only in PTRA + MSC-treated pigs. PTRA attenuated left ventricular remodeling, whereas myocardial oxygenation, subendocardial microvascular density, and diastolic function remained decreased in RVH + PTRA, but normalized in RVH + PTRA-MSC. Circulating isoprostane levels and renal release of inflammatory cytokines increased in RVH and RVH + PTRA, but normalized in RVH + PTRA-MSC, as did myocardial oxidative stress, inflammation, collagen deposition, and fibrosis. Intra-renal MSC delivery during PTRA preserved stenotic-kidney function, reduced systemic oxidative stress and inflammation, and thereby improved cardiac function, oxygenation, and myocardial injury four weeks after revascularization, suggesting a therapeutic potential for adjunctive MSC delivery to preserve cardiac function and structure after reversal of experimental RVH.

Transient severe left ventricular dysfunction following percutaneous patent ductus arteriosus closure in an adult with bicuspid aortic valve: A case report

PubMed Central

HWANG, HUI-JEONG; YOON, KYUNG LIM; SOHN, IL SUK

2016-01-01

The present study reported the case of a 60-year-old female with patent ductus arteriosus (PDA) and a bicuspid aortic valve, who presented with transient severe left ventricular (LV) dysfunction following percutaneous closure of PDA, as identified by speckle tracking analysis. Transient LV dysfunction following PDA closure has previously been reported; however, severe LV dysfunction is rare. In the present case, the combination of a large PDA size, large amount of shunting, LV remodeling and bicuspid aortic valve may have induced serious deterioration of LV function following PDA closure. Furthermore, speckle-tracking echocardiography may be useful in the estimation of functional alterations in the myocardium of the LV following PDA closure. The observations detailed in the present study may improve the understanding of the pathophysiology and myocardial patterns of transient left ventricular dysfunction following PDA closure in adult humans. PMID:26998021

Transient severe left ventricular dysfunction following percutaneous patent ductus arteriosus closure in an adult with bicuspid aortic valve: A case report.

PubMed

Hwang, Hui-Jeong; Yoon, Kyung Lim; Sohn, Il Suk

2016-03-01

The present study reported the case of a 60-year-old female with patent ductus arteriosus (PDA) and a bicuspid aortic valve, who presented with transient severe left ventricular (LV) dysfunction following percutaneous closure of PDA, as identified by speckle tracking analysis. Transient LV dysfunction following PDA closure has previously been reported; however, severe LV dysfunction is rare. In the present case, the combination of a large PDA size, large amount of shunting, LV remodeling and bicuspid aortic valve may have induced serious deterioration of LV function following PDA closure. Furthermore, speckle-tracking echocardiography may be useful in the estimation of functional alterations in the myocardium of the LV following PDA closure. The observations detailed in the present study may improve the understanding of the pathophysiology and myocardial patterns of transient left ventricular dysfunction following PDA closure in adult humans.

Role of Extracellular RNA and TLR3‐Trif Signaling in Myocardial Ischemia–Reperfusion Injury

PubMed Central

Chen, Chan; Feng, Yan; Zou, Lin; Wang, Larry; Chen, Howard H.; Cai, Jia‐Yan; Xu, Jun‐Mei; Sosnovik, David E.; Chao, Wei

2014-01-01

Background Toll‐like receptor 3 (TLR3) was originally identified as the receptor for viral RNA and represents a major host antiviral defense mechanism. TLR3 may also recognize extracellular RNA (exRNA) released from injured tissues under certain stress conditions. However, a role for exRNA and TLR3 in the pathogenesis of myocardial ischemic injury has not been tested. This study examined the role of exRNA and TLR3 signaling in myocardial infarction (MI), apoptosis, inflammation, and cardiac dysfunction during ischemia‐reperfusion (I/R) injury. Methods and Results Wild‐type (WT), TLR3−/−, Trif−/−, and interferon (IFN) α/β receptor‐1 deficient (IFNAR1−/−) mice were subjected to 45 minutes of coronary artery occlusion and 24 hours of reperfusion. Compared with WT, TLR3−/− or Trif−/− mice had smaller MI and better preserved cardiac function. Surprisingly, unlike TLR(2/4)‐MyD88 signaling, lack of TLR3‐Trif signaling had no impact on myocardial cytokines or neutrophil recruitment after I/R, but myocardial apoptosis was significantly attenuated in Trif−/− mice. Deletion of the downstream IFNAR1 had no effect on infarct size. Importantly, hypoxia and I/R led to release of RNA including microRNA from injured cardiomyocytes and ischemic heart, respectively. Necrotic cardiomyocytes induced a robust and dose‐dependent cytokine response in cultured cardiomyocytes, which was markedly reduced by RNase but not DNase, and partially blocked in TLR3‐deficient cardiomyocytes. In vivo, RNase administration reduced serum RNA level, attenuated myocardial cytokine production, leukocytes infiltration and apoptosis, and conferred cardiac protection against I/R injury. Conclusion TLR3‐Trif signaling represents an injurious pathway during I/R. Extracellular RNA released during I/R may contribute to myocardial inflammation and infarction. PMID:24390148

Hibernating myocardium, morphological studies on intraoperatory myocardial biopsies and on chronic ischemia experimental model.

PubMed

Laky, D; Parascan, Liliana

2007-01-01

Hibernating myocardium represent a prolonged but potentially reversible myocardial contractile dysfunction, an incomplete adaptation caused by chronic myocardial ischemia and persisting at least until blood flow restored. The purpose of this study was to investigate the morphological changes and weather relations exist among function, metabolism and structure in left ventricular hibernating myocardium. Material and methods. Experimental study is making on 12 dogs incomplete coronary obstruction during six weeks for morphologic studies of ischemic zones. On 48 patients with coronary stenosis myocardial biopsies was effectuated during aorto-coronarian bypass graft. On 60 patients with valvular disease associated with segmental coronary atherosclerotic obstructions during surgical interventions on a effectuated repeatedly biopsies from ischemic zones. Dyskinetic ischemic areas was identified by angiography, scintigraphy, low dose dobutamine echography to identify the cells viability. On myocardial biopsies various histological, histoenzymological, immunohistochemical and ultrastructural methods were performed. The morphological cardiomyocytic changes can summarized: loss of myofilaments, accumulation of glycogen, small mitochondria with reversible lesions, decrease of smooth reticulum, absence of T tubules, depression of titin in puncted pattern, loss of cardiotonin, disorganization of cytoskeleton, dispersed nuclear heterochromatin, embryofetal dedifferentiation, and persistence of viability. Extracellular matrix is enlarged with early matrix protein such fibronectin, tenascin, fibroblasts. In experimental material the morphological changes present similarities with the human biopsies, but intermixed with postinfarction scar tissue. Redifferentiation of hibernanting cells end remodeling of extracellular matrix is possible after quigle revascularization through aorto-coronary bypass grafts.

Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3β Activity.

PubMed

Shanmugam, Karthi; Ravindran, Sriram; Kurian, Gino A; Rajesh, Mohanraj

2018-01-01

Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. Timely reperfusion is considered an optimal treatment for AMI. Paradoxically, the procedure of reperfusion can itself cause myocardial tissue injury. Therefore, a strategy to minimize the reperfusion-induced myocardial tissue injury is vital for salvaging the healthy myocardium. Herein, we investigated the cardioprotective effects of fisetin, a natural flavonoid, against ischemia/reperfusion (I/R) injury (IRI) using a Langendorff isolated heart perfusion system. I/R produced significant myocardial tissue injury, which was characterized by elevated levels of lactate dehydrogenase and creatine kinase in the perfusate and decreased indices of hemodynamic parameters. Furthermore, I/R resulted in elevated oxidative stress, uncoupling of the mitochondrial electron transport chain, increased mitochondrial swelling, a decrease of the mitochondrial membrane potential, and induction of apoptosis. Moreover, IRI was associated with a loss of the mitochondrial structure and decreased mitochondrial biogenesis. However, when the animals were pretreated with fisetin, it significantly attenuated the I/R-induced myocardial tissue injury, blunted the oxidative stress, and restored the structure and function of mitochondria. Mechanistically, the fisetin effects were found to be mediated via inhibition of glycogen synthase kinase 3 β (GSK3 β ), which was confirmed by a biochemical assay and molecular docking studies.

THE AMPK ACTIVATOR AICAR AMELIORATES AGE-DEPENDENT MYOCARDIAL INJURY IN MURINE HEMORRHAGIC SHOCK

PubMed Central

Matsiukevich, Dzmitry; Piraino, Giovanna; Klingbeil, Lindsey R.; Hake, Paul W.; Wolfe, Vivian; O’Connor, Michael; Zingarelli, Basilia

2016-01-01

The development of myocardial dysfunction in patients with hemorrhagic shock is significantly impacted by the patient age. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of energy homeostasis, which coordinates metabolic recovery after cellular stress. We investigated whether AMPK-regulated pathways are age-dependent in hemorrhage-induced myocardial injury and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) affords cardioprotective effects. Anesthetized C57/BL6 young (3–5 months old) and mature male mice (9–12 months old) were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with shed blood and Lactated Ringer’s solution. Mice were sacrificed at 3 hours after resuscitation, and plasma and hearts were harvested for biochemical assays. Vehicle-treated mature mice exhibited higher myocardial injury and higher levels of plasma biomarkers of cardiovascular injury (endocan and follistatin) when compared with young mice. Cardiac cell mitochondrial structure was also markedly impaired in vehicle-treated mature mice when compared to young mice. At molecular analysis, an increase of the phosphorylated catalytic subunit pAMPKα was associated with nuclear translocation of the peroxisome proliferator-activated receptor γ co-activator-α in young, but not mature mice. No changes in autophagy were observed as evaluated by the conversion of the light-chain (LC)3B-I protein to LC3B-II form. Treatment with AICAR ameliorated myocardial damage in both age groups. However, AICAR therapeutic effects were less effective in mature mice compared to young mice and involved distinct mechanisms of action. Thus, our data demonstrate that during hemorrhagic shock AMPK-dependent metabolic mechanisms are important for mitigating myocardial injury. However, these mechanisms are less competent with age. PMID:27513082

The cardioprotective effect of salidroside against myocardial ischemia reperfusion injury in rats by inhibiting apoptosis and inflammation.

PubMed

Zhu, Lingpeng; Wei, Tingting; Gao, Jin; Chang, Xiayun; He, He; Luo, Fen; Zhou, Rui; Ma, Chunhua; Liu, Yu; Yan, Tianhua

2015-11-01

The main purpose of this study was to investigate effect of salidroside (Sal) on myocardial ischemia reperfusion injury in rats and the underlying mechanism. Myocardial ischemia reperfusion injury (MI/RI) model was treated with 30 min of left anterior descending (LAD) occlusion followed by 24 h of reperfusion. The male Sprague-Dawley rats were randomly divided into 7 groups: (1) Sham; (2) Sham + diltiazem (Dit, 10 mg/kg); (3) Sham + Sal (40 mg/kg); (4) I/R; (5) I/R + diltiazem (Dit, 10 mg/kg); (6) I/R + Sal (20 mg/kg); (7) I/R + Sal (40 mg/kg). Sal could ameliorate myocardial ischemia reperfusion injury as evidenced by Histopathological examination and triphenyl tetrazolium chloride (TTC) staining. Moreover, terminal deoxynucleotidyl transferase dUTP nickend labeling (TUNEL) assay demonstrated that Sal suppressed myocardial apoptosis, which may be related to up-regulation of Bcl-2/Bax ratio and inhibition of caspase-3, caspase-9 activation. Pretreatment with Sal affected serum biochemical parameters and cardiac dysfunction compared with I/R group. Sal also attenuated the pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in serum by inhibiting TLR4/NF-κB signaling pathway. Sal exerts strong favorable cardioprotective function on myocardial I/R injury which may relate to the down-regulation of the TLR4/NF-κB signaling pathway and the inhibition of cell apoptosis.

Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity.

PubMed

Bakkehaug, Jens Petter; Kildal, Anders Benjamin; Engstad, Erik Torgersen; Boardman, Neoma; Næsheim, Torvind; Rønning, Leif; Aasum, Ellen; Larsen, Terje Steinar; Myrmel, Truls; How, Ole-Jakob

2015-07-01

Omecamtiv mecarbil (OM) is a novel inotropic agent that prolongs systolic ejection time and increases ejection fraction through myosin ATPase activation. We hypothesized that a potentially favorable energetic effect of unloading the left ventricle, and thus reduction of wall stress, could be counteracted by the prolonged contraction time and ATP-consumption. Postischemic left ventricular dysfunction was created by repetitive left coronary occlusions in 7 pigs (7 healthy pigs also included). In both groups, systolic ejection time and ejection fraction increased after OM (0.75 mg/kg loading for 10 minutes, followed by 0.5 mg/kg/min continuous infusion). Cardiac efficiency was assessed by relating myocardial oxygen consumption to the cardiac work indices, stroke work, and pressure-volume area. To circumvent potential neurohumoral reflexes, cardiac efficiency was additionally assessed in ex vivo mouse hearts and isolated myocardial mitochondria. OM impaired cardiac efficiency; there was a 31% and 23% increase in unloaded myocardial oxygen consumption in healthy and postischemic pigs, respectively. Also, the oxygen cost of the contractile function was increased by 63% and 46% in healthy and postischemic pigs, respectively. The increased unloaded myocardial oxygen consumption was confirmed in OM-treated mouse hearts and explained by an increased basal metabolic rate. Adding the myosin ATPase inhibitor, 2,3-butanedione monoxide abolished all surplus myocardial oxygen consumption in the OM-treated hearts. Omecamtiv mecarbil, in a clinically relevant model, led to a significant myocardial oxygen wastage related to both the contractile and noncontractile function. This was mediated by that OM induces a continuous activation in resting myosin ATPase. © 2015 American Heart Association, Inc.

Flow-guided sketch and accentuated-tone adjusting for pencil drawing generation

NASA Astrophysics Data System (ADS)

Li, Ruirui; Yang, Lei; Hu, Wei

2017-07-01

Pencil drawing is an important artistic style which is widely used in draft sketch and finished rendering. It is non-trivial if we can automatically generate the pencil drawing more precisely in order to ease the human efforts. In this paper, we propose flow-guided sketch and accentuated-tone adjusting techniques to transform the pencil drawing from natural images. This work is extended from the existing pencil drawing framework where authors combine sketch and tone together for penciling purpose. Through an edge tangent flow guided classification and convolution, we can obtain more coherent and smooth strokes, especially for portraits. In addition, we also introduce a hierarchical approach to generate strokes. According to saliency map, we can adjust the tone of images automatically. The experimental results indicate the generated toned pencil drawings by our approach are of fewer artifacts and could even solve the images with dark background

Adeno-associated Virus Serotype 9 - Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction.

PubMed

Knezevic, Tijana; Myers, Valerie D; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K; Gordon, Jennifer; Weiner, Kristen N; Rabinowitz, Joseph; Ramsey, Frederick V; Tilley, Douglas G; Khalili, Kamel; Cheung, Joseph Y; Feldman, Arthur M

2016-12-01

The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. MI-BAG3 mice demonstrated a significantly (p < 0.0001) higher left ventricular ejection fraction (LVEF) 9 days after rAAV9-BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (p<0.05), increased systolic [Ca 2+ ] i , increased [Ca 2+ ] i transient amplitudes and increased maximal I Ca amplitude. The results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory and cell death signaling pathways in diabetic cardiomyopathy

PubMed Central

Rajesh, Mohanraj; Mukhopadhyay, Partha; Bátkai, Sándor; Patel, Vivek; Saito, Keita; Matsumoto, Shingo; Kashiwaya, Yoshihiro; Horváth, Béla; Mukhopadhyay, Bani; Becker, Lauren; Haskó, György; Liaudet, Lucas; Wink, David A; Veves, Aristidis; Mechoulam, Raphael; Pacher, Pál

2010-01-01

Objectives In this study, we have investigated the effects of cannabidiol (CBD) on myocardial dysfunction, inflammation, oxidative/nitrosative stress, cell death and interrelated signaling pathways, using a mouse model of type I diabetic cardiomyopathy and primary human cardiomyocytes exposed to high glucose. Background CBD, the most abundant nonpsychoactive constituent of Cannabis sativa (marijuana) plant, exerts antiinflammatory effects in various disease models and alleviates pain and spasticity associated with multiple sclerosis in humans. Methods Left ventricular function was measured by pressure-volume system. Oxidative stress, cell death and fibrosis markers were evaluated by molecular biology/biochemical techniques, electron spin resonance spectroscopy and flow cytometry. Results Diabetic cardiomyopathy was characterized by declined diastolic and systolic myocardial performance associated with increased oxidative-nitrosative stress, NF-κB and MAPK (JNK and p-38, p38α) activation, enhanced expression of adhesion molecules (ICAM-1, VCAM-1), TNF-α, markers of fibrosis (TGF-β, CTGF, fibronectin, collagen-1, MMP-2 and MMP-9), enhanced cell death (caspase 3/7 and PARP activity, chromatin fragmentation and TUNEL) and diminished Akt phosphorylation. Remarkably, CBD attenuated myocardial dysfunction, cardiac fibrosis, oxidative/nitrosative stress, inflammation, cell death, and interrelated signaling pathways. Furthermore, CBD also attenuated the high glucose-induced increased reactive oxygen species generation, NF-κB activation and cell death in primary human cardiomyocytes. Conclusions Collectively, these results coupled with the excellent safety and tolerability profile of cannabidiol in humans, strongly suggest that it may have great therapeutic potential in the treatment of diabetic complications, and perhaps other cardiovascular disorders, by attenuating oxidative/nitrosative stress, inflammation, cell death and fibrosis. PMID:21144973

EXOGENOUS CYTOCHROME C RESTORES MYOCARDIAL CYTOCHROME OXIDASE ACTIVITY INTO THE LATE PHASE OF SEPSIS

PubMed Central

Piel, David A.; Deutschman, Clifford S.; Levy, Richard J.

2009-01-01

Mitochondrial dysfunction is thought to play a role in the pathogenesis of a variety of disease states, including sepsis. An acquired defect in oxidative phosphorylation potentially causes sepsis-induced organ dysfunction. Cytochrome oxidase (CcOX), the terminal oxidase of the respiratory chain, is competitively inhibited early in sepsis and progresses, becoming noncompetitive during the late phase. We have previously demonstrated that exogenous cytochrome c can overcome myocardial CcOX competitive inhibition and improve cardiac function during murine sepsis at the 24-h point. Here, we evaluate the effect of exogenous cytochrome c on CcOX activity and survival in mice at the later time points. Exogenous cytochrome c (800 μg) or saline was intravenously injected 24 h after cecal ligation and puncture (CLP) or sham operation. Steady-state mitochondrial cytochrome c levels and heme c content increased significantly 48 h post-CLP and remained elevated at 72 h in cytochrome c-injected mice compared with saline injection. Cecal ligation and puncture inhibited CcOX at 48 h in saline-injected mice. However, cytochrome c injection abrogated this inhibition and restored CcOX kinetic activity to sham values at 48 h. Survival after CLP to 96 h after cytochrome c injection approached 50% compared with only 15% after saline injection. Thus, a single injection of exogenous cytochrome c 24 h post-CLP repletes mitochondrial substrate levels for up to 72 h, restores myocardial COX activity, and significantly improves survival. PMID:18414235

Positron emission tomography for the assessment of myocardial viability: an evidence-based analysis.

PubMed

2010-01-01

emission tomography (PET) imaging using F-18-fluorodeoxyglucose (FDG) for the assessment of myocardial viability. To evaluate the effectiveness of FDG PET viability imaging, the following outcomes are examined: the diagnostic accuracy of FDG PET for predicting functional recovery;the impact of PET viability imaging on prognosis (mortality and other patient outcomes); andthe contribution of PET viability imaging to treatment decision making and subsequent patient outcomes. CONDITION AND TARGET POPULATION LEFT VENTRICULAR SYSTOLIC DYSFUNCTION AND HEART FAILURE: Heart failure is a complex syndrome characterized by the heart's inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. IN GENERAL, THERE ARE THREE OPTIONS FOR THE TREATMENT OF HEART FAILURE: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore

It's a trap! Clinical similarities and subtle ECG differences between takotsubo cardiomyopathy and myocardial infarction.

PubMed

Vivo, Rey P; Krim, Selim R; Hodgson, John

2008-11-01

We describe a 65-year-old woman with a history of hypertension and smoking who presented with an acute episode of chest pain precipitated by severe emotional stress. Her initial electrocardiogram done in the emergency room showed non-specific T wave changes in the lateral leads and her cardiac troponin levels were mildly elevated. Because of her clinical presentation, she was admitted with a presumptive diagnosis of acute myocardial infarction and managed with antiplatelet and anticoagulant therapy. Coronary angiogram did not reveal coronary artery disease and left ventriculography showed findings consistent with apical ballooning syndrome or takotsubo cardiomyopathy. Subsequent electrocardiograms displayed dramatic changes including T wave inversions, QT interval prolongation and U waves. The patient remained asymptomatic and recovered uneventfully. Three weeks post-discharge, an echocardiogram documented resolved left ventricular dysfunction. We describe the clinical features and highlight the electrocardiographic findings that may help differentiate takotsubo cardiomyopathy from myocardial infarction.

The inflammatory response in myocardial injury, repair and remodeling

PubMed Central

Frangogiannis, Nikolaos G.

2015-01-01

Myocardial infarction triggers an intense inflammatory response that is essential for cardiac repair, but which is also implicated in the pathogenesis of post-infarction remodeling and heart failure. Signals in the infarcted myocardium activate toll-like receptor signalling, while complement activation and generation of reactive oxygen species induce cytokine and chemokine upregulation. Leukocytes recruited remove dead cells and matrix debris by phagocytosis, while setting the stage for scar formation. Timely repression of the inflammatory response is critical for effective healing and followed by activation of infarct myofibroblasts that secrete matrix proteins in the infarcted area. Members of the transforming growth factor-β family are critically involved in suppression of inflammation and activation of a pro-fibrotic program. Translation of these concepts in the clinic requires understanding of the pathophysiologic complexity and heterogeneity of post-infarction remodeling in human patients with myocardial infarction. Individuals with overactive and prolonged post-infarction inflammation might exhibit dilation and systolic dysfunction and benefit from targeted anti-IL-1 or anti-chemokine therapies, whereas patients with exaggerated fibrogenic reactions can develop diastolic heart failure and might require inhibition of the smad3 cascade. Biomarker-based approaches are needed to identify patients with distinct pathophysiologic responses and to rationally implement inflammation-modulating strategies. PMID:24663091

Cardioprotective effects of red wine and vodka in a model of endothelial dysfunction

PubMed Central

Lassaletta, Antonio D; Chu, Louis M; Elmadhun, Nassrene Y; Burgess, Thomas A; Feng, Jun; Robich, Michael P; Sellke, Frank W

2012-01-01

Background Moderate alcohol consumption is largely believed to be cardioprotective, while red wine is hypothesized to offer benefit in part due to the pro-angiogenic and antioxidant properties of polyphenols. We investigated the cardiovascular effects of both red wine and vodka in a swine model of endothelial dysfunction. Methods Twenty-seven male Yorkshire swine fed a high-fat/cholesterol diet were divided into three groups and received either no alcohol (Control), red wine, or vodka. After seven weeks, myocardial perfusion was measured, and ventricular tissue was analyzed for microvascular reactivity, and immunohistochemical studies. Results There were no differences in myocardial perfusion, in arteriolar or capillary density, or in VEGF expression among groups. Total protein oxidation as well as expression of superoxide dismutase-1 and -2 (SOD1, SOD2) and NADPH-oxidase (NOX2) was decreased in both treatment groups compared to controls. Endothelium-dependent microvessel relaxation, however, was significantly improved only in the red wine-supplemented group. Conclusions Supplementation with both red wine and vodka decreased oxidative stress by several measures, implicating the effects of ethanol in reducing oxidative stress in the myocardium. However, it was only in the red wine-supplemented group that an improvement in microvessel function was observed. This suggests that a component of red wine, independent of ethanol, possibly a polyphenol such as resveratrol, may confer cardioprotection by normalizing endothelial dysfunction induced by an atherogenic diet. PMID:22748601

Doppler-derived myocardial performance index in patients with impaired left ventricular relaxation and preserved systolic function.

PubMed

Fernandes, José Maria G; Rivera, Ivan Romero; de Oliveira Romão, Benício; Mendonça, Maria Alayde; Vasconcelos, Miriam Lira Castro; Carvalho, Antônio Carlos; Campos, Orlando; De Paola, Angelo Amato V; Moisés, Valdir A

2009-09-01

The Doppler-derived myocardial performance index (MPI) has been used in the evaluation of left ventricular (LV) function in several diseases. In patients with isolated diastolic dysfunction, the diagnostic utility of this index remains unclear. The aim of this study was to determine the diagnostic utility of MPI in patients with systemic hypertension, impaired LV relaxation, and normal ejection fraction. Thirty hypertensive patients with impaired LV relaxation were compared to 30 control subjects. MPI and its components, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), and the ejection time (ET), were measured from LV outflow and mitral inflow Doppler velocity profiles. MPI was higher in patients than in control subjects (0.45 +/- 0.13 vs 0.37 +/- 0.07 P < 0.0029). The increase in MPI was due to the prolongation of IRT without significant change of ICT and ET. MPI cutoff value of > or =0.40 identified impaired LV relaxation with a sensitivity of 63% and specificity of 70% while an IRT >94 ms had a sensitivity of 67% and specificity of 80%. Multivariate analysis identified relative wall thickness, mitral early filling wave velocity (E), and systolic myocardial velocity (Sm) as independent predictors of MPI in patients with hypertension. MPI was increase in patients with hypertension, diastolic dysfunction, and normal ejection fraction but was not superior to IRT to detect impaired LV relaxation.

Vitamin D attenuates pressure overload-induced cardiac remodeling and dysfunction in mice.

PubMed

Zhang, Liang; Yan, Xiao; Zhang, Yun-Long; Bai, Jie; Hidru, Tesfaldet Habtemariam; Wang, Qing-Shan; Li, Hui-Hua

2018-04-01

Vitamin D (VD) and its analogues play critical roles in metabolic and cardiovascular diseases. Recent studies have demonstrated that VD exerts a protective role in cardiovascular diseases. However, the beneficial effect of VD on pressure overload-induced cardiac remodeling and dysfunction and its underlying mechanisms are not fully elucidated. In this study, cardiac dysfunction and hypertrophic remodeling in mice were induced by pressure overload. Cardiac function was evaluated by echocardiography, and myocardial histology was detected by H&E and Masson's trichrome staining. Cardiomyocyte size was detected by wheat germ agglutinin staining. The protein levels of signaling mediators were examined by western blotting while mRNA expression of hypertrophic and fibrotic markers was examined by qPCR analysis. Oxidative stress was detected by dihydroethidine staining. Our results showed that administration of VD3 significantly ameliorates pressure overload-induced contractile dysfunction, cardiac hypertrophy, fibrosis and inflammation in mice. In addition, VD3 treatment also markedly inhibited cardiac oxidative stress and apoptosis. Moreover, protein levels of calcineurin A, ERK1/2, AKT, TGF-β, GRP78, cATF6, and CHOP were significantly reduced whereas SERCA2 level was upregulated in the VD3-treated hearts compared with control. These results suggest that VD3 attenuates cardiac remodeling and dysfunction induced by pressure overload, and this protective effect is associated with inhibition of multiple signaling pathways. Copyright © 2018 Elsevier Ltd. All rights reserved.

Myocardial contusion in patients with blunt chest trauma as evaluated by thallium 201 myocardial scintigraphy

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

Bodin, L.; Rouby, J.J.; Viars, P.

1988-07-01

Fifty five patients suffering from blunt chest trauma were studied to assess the diagnosis of myocardial contusion using thallium 201 myocardial scintigraphy. Thirty-eight patients had consistent scintigraphic defects and were considered to have a myocardial contusion. All patients with scintigraphic defects had paroxysmal arrhythmias and/or ECG abnormalities. Of 38 patients, 32 had localized ST-T segment abnormalities; 29, ST-T segment abnormalities suggesting involvement of the same cardiac area as scintigraphic defects; 21, echocardiographic abnormalities. Sixteen patients had segmental hypokinesia involving the same cardiac area as the scintigraphic defects. Fifteen patients had clinical signs suggestive of myocardial contusion and scintigraphic defects. Almostmore » 70 percent of patients with blunt chest trauma had scintigraphic defects related to areas of myocardial contusion. When thallium 201 myocardial scintigraphy directly showed myocardial lesion, two-dimensional echocardiography and standard ECG detected related functional consequences of cardiac trauma.« less

Experimental myocardial infarction

PubMed Central

Kumar, Raj; Joison, Julio; Gilmour, David P.; Molokhia, Farouk A.; Pegg, C. A. S.; Hood, William B.

1971-01-01

The hemodynamic effects of tachycardia induced by atrial pacing were investigated in left ventricular failure of acute and healing experimental myocardial infarction in 20 intact, conscious dogs. Myocardial infarction was produced by gradual inflation of a balloon cuff device implanted around the left anterior descending coronary artery 10-15 days prior to the study. 1 hr after acute myocardial infarction, atrial pacing at a rate of 180 beats/min decreased left ventricular end-diastolic pressure from 19 to 8 mm Hg and left atrial pressure from 17 to 12 mm Hg, without change in cardiac output. In the healing phase of myocardial infarction 1 wk later, atrial pacing decreased left ventricular end-diastolic pressure from 17 to 9 mm Hg and increased the cardiac output by 37%. This was accompanied by evidence of peripheral vasodilation. In two dogs with healing anterior wall myocardial infarction, left ventricular failure was enhanced by partial occlusion of the circumflex coronary artery. Both the dogs developed pulmonary edema. Pacing improved left ventricular performance and relieved pulmonary edema in both animals. In six animals propranolol was given after acute infarction, and left ventricular function deteriorated further. However the pacing-induced augmentation of cardiac function was unaltered and, hence, is not mediated by sympathetics. The results show that the spontaneous heart rate in left ventricular failure of experimental canine myocardial infarction may be less than optimal and that maximal cardiac function may be achieved at higher heart rates. Images PMID:4395910

Adeno-associated Virus Serotype 9 – Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction

PubMed Central

Knezevic, Tijana; Myers, Valerie D.; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K.; Gordon, Jennifer; Weiner, Kristen N.; Rabinowitz, Joseph; Ramsey, Frederick V.; Tilley, Douglas G.; Khalili, Kamel; Cheung, Joseph Y.; Feldman, Arthur M.

2016-01-01

Objectives The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. Background BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Methods Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. Results MI-BAG3 mice demonstrated a significantly (p < 0.0001) higher left ventricular ejection fraction (LVEF) 9 days after rAAV9-BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (p<0.05), increased systolic [Ca2+]i, increased [Ca2+]i transient amplitudes and increased maximal ICa amplitude. Implications The results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure. PMID:28164169

Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion.

PubMed

Maity, Sangeeta; Kar, Dipak; De, Kakali; Chander, Vivek; Bandyopadhyay, Arun

2013-05-01

This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism. Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition. Ultrastructure of mitochondria was damaged in T3-treated rat heart, which was prevented by Bzf co-administration. Hyperthyroidism-induced oxidative stress, reduction in cytochrome c oxidase activity, and myocardial ATP concentration were also significantly checked by Bzf. Heart function studied at different time points during the course of T3 treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment. In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.

Evolution of echocardiography in subclinical detection of cancer therapy-related cardiac dysfunction.

PubMed

Moudgil, Rohit; Hassan, Saamir; Palaskas, Nicolas; Lopez-Mattei, Juan; Banchs, Jose; Yusuf, Syed Wamique

2018-05-11

Cancer therapies have resulted in increased survivorship in oncological patients. However, the benefits have been marred by the development of premature cardiovascular disease. The current definition outlines measurement of ejection fraction as a mean to diagnose cancer therapeutic-related cardiac dysfunction (CTRCD); however, up to 58% of the patients do not regain their cardiac function after the CTRCD diagnosis, despite therapeutic interventions. Therefore, there has been a growing interest in the markers for early myocardial changes (ie, changes with normal left ventricular ejection fraction [LVEF]) that may predict the development of subsequent left ventricular ejection fraction reduction or progression to heart failure. This review will highlight the use of diastolic parameters, tissue Doppler imaging (TDI), and speckle tracking echocardiogram (STE) as emerging technologies which can potentially detect cardiac dysfunction thereby stratifying patients for cardioprotective therapies. The goal of this manuscript was to highlight the concepts and discuss the current controversies surrounding these echocardiographic imaging modalities. © 2018 Wiley Periodicals, Inc.

Extracts of Crataegus oxyacantha and Rosmarinus officinalis Attenuate Ischemic Myocardial Damage by Decreasing Oxidative Stress and Regulating the Production of Cardiac Vasoactive Agents.

PubMed

Cuevas-Durán, Raúl Enrique; Medrano-Rodríguez, Juan Carlos; Sánchez-Aguilar, María; Soria-Castro, Elizabeth; Rubio-Ruíz, María Esther; Del Valle-Mondragón, Leonardo; Sánchez-Mendoza, Alicia; Torres-Narvaéz, Juan Carlos; Pastelín-Hernández, Gustavo; Ibarra-Lara, Luz

2017-11-14

Numerous studies have supported a role for oxidative stress in the development of ischemic damage and endothelial dysfunction. Crataegus oxyacantha ( Co ) and Rosmarinus officinalis ( Ro ) extracts are polyphenolic-rich compounds that have proven to be efficient in the treatment of cardiovascular diseases. We studied the effect of extracts from Co and Ro on the myocardial damage associated with the oxidative status and to the production of different vasoactive agents. Rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); (c) Ro extract-treated myocardial infarction (MI- Ro ); (d) Co extract-treated myocardial infarction (MI- Co ); or (e) Ro+Co -treated myocardial infarction (MI- Ro+Co ). Ro and Co treatments increased total antioxidant capacity, the expression of superoxide dismutase (SOD)-Cu 2+ /Zn 2+ , SOD-Mn 2+ , and catalase, with the subsequent decline of malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. The extracts diminished vasoconstrictor peptide levels (angiotensin II and endothelin-1), increased vasodilators agents (angiotensin 1-7 and bradikinin) and improved nitric oxide metabolism. Polyphenol treatment restored the left intraventricular pressure and cardiac mechanical work. We conclude that Ro and Co treatment attenuate morphological and functional ischemic-related changes by both an oxidant load reduction and improvement of the balance between vasoconstrictors and vasodilators.

Extracts of Crataegus oxyacantha and Rosmarinus officinalis Attenuate Ischemic Myocardial Damage by Decreasing Oxidative Stress and Regulating the Production of Cardiac Vasoactive Agents

PubMed Central

Cuevas-Durán, Raúl Enrique; Medrano-Rodríguez, Juan Carlos; Sánchez-Aguilar, María; Soria-Castro, Elizabeth; Del Valle-Mondragón, Leonardo; Sánchez-Mendoza, Alicia; Torres-Narvaéz, Juan Carlos; Pastelín-Hernández, Gustavo; Ibarra-Lara, Luz

2017-01-01

Numerous studies have supported a role for oxidative stress in the development of ischemic damage and endothelial dysfunction. Crataegus oxyacantha (Co) and Rosmarinus officinalis (Ro) extracts are polyphenolic-rich compounds that have proven to be efficient in the treatment of cardiovascular diseases. We studied the effect of extracts from Co and Ro on the myocardial damage associated with the oxidative status and to the production of different vasoactive agents. Rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); (c) Ro extract-treated myocardial infarction (MI-Ro); (d) Co extract-treated myocardial infarction (MI-Co); or (e) Ro+Co-treated myocardial infarction (MI-Ro+Co). Ro and Co treatments increased total antioxidant capacity, the expression of superoxide dismutase (SOD)-Cu2+/Zn2+, SOD-Mn2+, and catalase, with the subsequent decline of malondialdehyde and 8-hydroxy-2′-deoxyguanosine levels. The extracts diminished vasoconstrictor peptide levels (angiotensin II and endothelin-1), increased vasodilators agents (angiotensin 1–7 and bradikinin) and improved nitric oxide metabolism. Polyphenol treatment restored the left intraventricular pressure and cardiac mechanical work. We conclude that Ro and Co treatment attenuate morphological and functional ischemic-related changes by both an oxidant load reduction and improvement of the balance between vasoconstrictors and vasodilators. PMID:29135932

Inhibition of Drp1 attenuates mitochondrial damage and myocardial injury in Coxsackievirus B3 induced myocarditis

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

Lin, Lin; Zhang, Ming; Yan, Rui

Viral myocarditis (VMC) is closely related to apoptosis, oxidative stress, innate immunity, and energy metabolism, which are all linked to mitochondrial dysfunction. A close nexus between mitochondrial dynamics and cardiovascular disease with mitochondrial dysfunction has been deeply researched, but there is still no relevant report in viral myocarditis. In this study, we aimed to explore the role of Dynamin-related protein 1 (Drp1)-linked mitochondrial fission in VMC. Mice were inoculated with the Coxsackievirus B3 (CVB3) and treated with mdivi1 (a Drp1 inhibitor). Protein expression of Drp1 was increased in mitochondria while decreased in cytoplasm and accompanied by excessive mitochondrial fission inmore » VMC mice. In addition, midivi1 treatment attenuate inflammatory cells infiltration in myocardium of the mice, serum Cardiac troponin I (CTnI) and Creatine kinase-MB (CK-MB) level. Mdivi1 also could improved the survival rate of mice and mitochondrial dysfunction reflected as the up-regulated mitochondrial marker enzymatic activities of succinate dehydrogenase (SDH), cytochrome c oxidase (COX) and mitochondrial membrane potential (MMP). At the same time, mdivi1 rescued the body weight loss, myocardial injury and apoptosis of cardiomyocyte. Furthermore, decease in LVEDs and increase in EF and FS were detected by echocardiogram, which indicated the improved myocardial function. Thus, Drp1-linked excessive mitochondrial fission contributed to VMC and midivi1 may be a potential therapeutic approach. - Highlights: • The expression of Drp1 is significantly increased in mitochondria while decreased in cytoplasm in VMC mice. • Drp1-linked excessive mitochondrial fission is involved in VMC. • Midivi1 treatment mitigate the mitochondrial damage, inflammation, apoptosis in VMC mice. • The disturbance of mitochondrial dynamics may be a new therapeutic target for VMC.« less

Case report: paradoxical ventricular septal motion in the setting of primary right ventricular myocardial failure.

PubMed

Maslow, Andrew; Schwartz, Carl; Mahmood, Feroze; Singh, Arun; Heerdt, Paul M

2009-07-01

In this report, a case of right ventricular (RV) failure, hemodynamic instability, and systemic organ failure is described to highlight how paradoxical ventricular systolic septal motion (PVSM), or a rightward systolic displacement of the interventricular septum, may contribute to RV ejection. Multiple inotropic medications and vasopressors were administered to treat right heart failure and systemic hypotension in a patient following combined aortic and mitral valve replacement. In the early postoperative period, echocardiographic evaluation revealed adequate left ventricular systolic function, akinesis of the RV myocardial tissues, and PVSM. In the presence of PVSM, RV fractional area of contraction was > or =35% despite akinesis of the primary RV myocardial walls. The PVSM appeared to contribute toward RV ejection. As a result, the need for multiple inotropes was re-evaluated, in considering that end-organ dysfunction was the result of systemic hypotension and prolonged vasopressor administration. After discontinuation of phosphodiesterase inhibitors, native vascular tone returned and the need for vasopressors declined. This was followed by recovery of systemic organ function. Echocardiographic re-evaluation two years later, revealed persistent akinesis of the RV myocardial tissues and PVSM, the latter appearing to contribute toward RV ejection. This case highlights the importance of left to RV interactions, and how PVSM may mediate these hemodynamic interactions.

Toll-like receptor 2 mediates mesenchymal stem cell-associated myocardial recovery and VEGF production following acute ischemia-reperfusion injury

PubMed Central

Abarbanell, Aaron M.; Wang, Yue; Herrmann, Jeremy L.; Weil, Brent R.; Poynter, Jeffrey A.; Manukyan, Mariuxi C.

2010-01-01

Toll-like receptor 2 (TLR2), a key component of the innate immune system, is linked to inflammation and myocardial dysfunction after ischemia-reperfusion injury (I/R). Treatment of the heart with mesenchymal stem cells (MSCs) is known to improve myocardial recovery after I/R in part by paracrine factors such as VEGF. However, it is unknown whether TLR2 activation on the MSCs affects MSC-mediated myocardial recovery and VEGF production. We hypothesized that the knockout of TLR2 on the MSCs (TLR2KO MSCs) would 1) improve MSC-mediated myocardial recovery and 2) increase myocardial and MSC VEGF release. With the isolated heart perfusion system, Sprague-Dawley rat hearts were subjected to I/R and received one of three intracoronary treatments: vehicle, male wild-type MSCs (MWT MSCs), or TL2KO MSCs. All treatments were performed immediately before ischemia, and heart function was measured continuously. Postreperfusion, heart homogenates were analyzed for myocardial VEGF production. Contrary to our hypothesis, only MWT MSC treatment significantly improved the recovery of left ventricular developed pressure and the maximal positive and negative values of the first derivative of pressure. In addition, VEGF production was greatest in hearts treated with MWT MSCs. To investigate MSC production of VEGF, MSCs were activated with TNF in vitro and the supernatants collected for ELISA. In vitro basal levels of MSC VEGF production were similar. However, with TNF activation, MWT MSCs produced significantly more VEGF, whereas activated TLR2KO MSC production of VEGF was unchanged. Finally, we observed that MWT MSCs proliferated more rapidly than TLR2KO MSCs. These data indicate that TLR2 may be essential to MSC-mediated myocardial recovery and VEGF production. PMID:20173040

Effect of hypercholesterolaemia on myocardial function, ischaemia–reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning

PubMed Central

Iliodromitis, Efstathios K; Lazou, Antigone; Görbe, Anikó; Giricz, Zoltán; Schulz, Rainer

2017-01-01

Hypercholesterolaemia is considered to be a principle risk factor for cardiovascular disease, having direct negative effects on the myocardium itself, in addition to the development of atherosclerosis. Since hypercholesterolaemia affects the global cardiac gene expression profile, among many other factors, it results in increased myocardial oxidative stress, mitochondrial dysfunction and inflammation triggered apoptosis, all of which may account for myocardial dysfunction and increased susceptibility of the myocardium to infarction. In addition, numerous experimental and clinical studies have revealed that hyperlcholesterolaemia may interfere with the cardioprotective potential of conditioning mechanisms. Although not fully elucidated, the underlying mechanisms for the lost cardioprotection in hypercholesterolaemic animals have been reported to involve dysregulation of the endothelial NOS‐cGMP, reperfusion injury salvage kinase, peroxynitrite‐MMP2 signalling pathways, modulation of ATP‐sensitive potassium channels and apoptotic pathways. In this review article, we summarize the current knowledge on the effect of hypercholesterolaemia on the non‐ischaemic and ischaemic heart as well as on the cardioprotection induced by drugs or ischaemic preconditioning, postconditioning and remote conditioning. Future perspectives concerning the mechanisms and the design of preclinical and clinical trials are highlighted. Linked Articles This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc PMID:28060997

Moderate elevation of intracellular creatine by targeting the creatine transporter protects mice from acute myocardial infarction

PubMed Central

Lygate, Craig A.; Bohl, Steffen; ten Hove, Michiel; Faller, Kiterie M.E.; Ostrowski, Philip J.; Zervou, Sevasti; Medway, Debra J.; Aksentijevic, Dunja; Sebag-Montefiore, Liam; Wallis, Julie; Clarke, Kieran; Watkins, Hugh; Schneider, Jürgen E.; Neubauer, Stefan

2012-01-01

Aims Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We therefore used mice overexpressing creatine transporter in the heart (CrT-OE) to test for the first time whether elevated creatine is beneficial in clinically relevant disease models of heart failure and ischaemia/reperfusion (I/R) injury. Methods and results CrT-OE mice were selected for left ventricular (LV) creatine 20–100% above wild-type values and subjected to acute and chronic coronary artery ligation. Increasing myocardial creatine up to 100% was not detrimental even in ageing CrT-OE. In chronic heart failure, creatine elevation was neither beneficial nor detrimental, with no effect on survival, LV remodelling or dysfunction. However, CrT-OE hearts were protected against I/R injury in vivo in a dose-dependent manner (average 27% less myocardial necrosis) and exhibited greatly improved functional recovery following ex vivo I/R (59% of baseline vs. 29%). Mechanisms contributing to ischaemic protection in CrT-OE hearts include elevated PCr and glycogen levels and improved energy reserve. Furthermore, creatine loading in HL-1 cells did not alter antioxidant defences, but delayed mitochondrial permeability transition pore opening in response to oxidative stress, suggesting an additional mechanism to prevent reperfusion injury. Conclusion Elevation of myocardial creatine by 20–100% reduced myocardial stunning and I/R injury via pleiotropic mechanisms, suggesting CrT activation as a novel, potentially translatable target for cardiac protection from ischaemia. PMID:22915766

Ca(2+) mishandling and cardiac dysfunction in obesity and insulin resistance: role of oxidative stress.

PubMed

Carvajal, Karla; Balderas-Villalobos, Jaime; Bello-Sanchez, Ma Dolores; Phillips-Farfán, Bryan; Molina-Muñoz, Tzindilu; Aldana-Quintero, Hugo; Gómez-Viquez, Norma L

2014-11-01

Obesity and insulin resistance (IR) are strongly connected to the development of subclinical cardiac dysfunction and eventually can lead to heart failure, which is the main cause of morbidity and death in patients having these metabolic diseases. It has been considered that excessive fat tissue may play a critical role in producing systemic IR and enhancing reactive oxygen species (ROS) generation. This oxidative stress (OS) may elicit or exacerbate IR. On the other hand, evidence suggests that some of the cellular mechanisms involved in the pathophysiology of obesity and IR-related cardiomyopathy are excessive myocardial ROS production and abnormal Ca(2+) homeostasis. In addition, emerging evidence suggests that augmented ROS production may contribute to Ca(2+) mishandling by affecting the redox state of key proteins implicated in this process. In this review, we focus on the role of Ca(2+) mishandling in the development of cardiac dysfunction in obesity and IR and address the evidence suggesting that OS might also contribute to cardiac dysfunction by affecting Ca(2+) handling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of diastolic dysfunction on postoperative outcomes after cardiovascular surgery: A systematic review and meta-analysis.

PubMed

Kaw, Roop; Hernandez, Adrian V; Pasupuleti, Vinay; Deshpande, Abhishek; Nagarajan, Vijaiganesh; Bueno, Hector; Coleman, Craig I; Ioannidis, John P A; Bhatt, Deepak L; Blackstone, Eugene H

2016-10-01

The objective of this study was to investigate the effect of preoperative diastolic dysfunction on postoperative mortality and morbidity after cardiovascular surgery. We systematically searched for articles that assessed the prognostic role of diastolic dysfunction on cardiovascular surgery in PubMed, Cochrane Library, Web of Science, Embase, and Scopus until February 2016. Twelve studies (n = 8224) met our inclusion criteria. Because of the scarcity of outcome events, fixed-effects meta-analysis was performed via the Mantel-Haenszel method. Preoperative diagnosis of diastolic dysfunction was associated with greater postoperative mortality (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.54-3.71; P < .0001), major adverse cardiac events (OR, 2.07; 95% CI, 1.55-2.78; P ≤ .0001), and prolonged mechanical ventilation (OR, 2.08; 95% CI, 1.04-4.16; P = .04) compared with patients without diastolic dysfunction among patients who underwent cardiovascular surgery. The odds of postoperative myocardial infarction (OR, 1.29; 95% CI, 0.82-2.05; P = .28) and atrial fibrillation (OR, 2.67; 95% CI, 0.49-14.43; P = .25) did not significantly differ between the 2 groups. Severity of preoperative diastolic dysfunction was associated with increased postoperative mortality (OR, 21.22; 95% CI, 3.74-120.33; P = .0006) for Grade 3 diastolic dysfunction compared with patients with normal diastolic function. Inclusion of left ventricular ejection fraction (LVEF) <40% accompanying diastolic dysfunction did not further impact postoperative mortality (P = .27; I(2) = 18%) compared with patients with normal LVEF and diastolic dysfunction. Presence of preoperative diastolic dysfunction was associated with greater postoperative mortality and major adverse cardiac events, regardless of LVEF. Mortality was significantly greater in grade III diastolic dysfunction. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights

Role of microtubules in the contractile dysfunction of hypertrophied myocardium

NASA Technical Reports Server (NTRS)

Zile, M. R.; Koide, M.; Sato, H.; Ishiguro, Y.; Conrad, C. H.; Buckley, J. M.; Morgan, J. P.; Cooper, G. 4th

1999-01-01

OBJECTIVES: We sought to determine whether the ameliorative effects of microtubule depolymerization on cellular contractile dysfunction in pressure overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective and persistent increase in microtubule density causes decreased contractile function of cardiocytes from cats with hypertrophy produced by chronic right ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine normalizes contractility in these isolated cardiocytes. However, whether these changes in cellular function might contribute to changes in function at the more highly integrated and complex cardiac tissue level was unknown. METHODS: Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25 control cats. Contractile state was measured using physiologically sequenced contractions before and 90 min after treatment with 10(-5) mol/liter colchicine. RESULTS: The PAB significantly increased RV systolic pressure and the RV weight/body weight ratio in PAB; it significantly decreased developed tension from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from 0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB. Indirect immunofluorescence confocal microscopy showed that PAB muscles had a selective increase in microtubule density and that colchicine caused complete microtubule depolymerization in both control and PAB papillary muscles. Microtubule depolymerization normalized myocardial contractility in papillary muscles of PAB cats but did not alter contractility in control muscles. CONCLUSIONS: Excess microtubule density, therefore, is equally important to both cellular and to myocardial contractile dysfunction caused by chronic, severe pressure-overload cardiac hypertrophy.

QT/RR relationship in patients after remote anterior myocardial infarction with left ventricular dysfunction and different types of ventricular arrhythmias.

PubMed

Szydlo, Krzysztof; Trusz-Gluza, Maria; Wita, Krystian; Filipecki, Artur; Orszulak, Witold; Urbanczyk, Dagmara; Krauze, Jolanta; Kolasa, Jaroslaw; Tabor, Zbigniew

2008-01-01

QT/RR relationship was found to be both rate-dependent and rate-independent, what suggests the influence of autonomic drive and other not-autonomic related factors on it. The steeper QT/RR slope in patients after acute myocardial infarction (MI) was described, but the relationship to ventricular arrhythmias is unknown. The purpose of this study was to calculate differences in QT/RR relationship in patients after remote anterior MI with left ventricular dysfunction and different types of ventricular arrhythmias. The cohort of 95 patients (age: 63 +/- 11 years, LVEF: 35 +/- 9%) with previous anterior MI (mean 1.1 years) was divided into two well-matched groups-50 patients without episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) (NoVT/VF: 39 males, 64 +/- 12 years, LVEF 37 +/- 8%) and 45 patients with VT and/or VF (all with ICD implanted) (VT/VF: 35 males, 62 +/- 10 years, LVEF 34 +/- 10%). No true antiarrhythmics were used. QT/RR slope was calculated from 24-hour Holter ECG for the entire recording (E), daytime (D) and nighttime (N) periods. Groups did not differ in basic clinical data (age, LVEF, treatment). QT/RR slopes were steeper in VT/VF than in NoVT/VF group in all analyzed periods: E - 0.195 +/- 0.03 versus 0.15 +/- 0.03 (P < 0.001), N - 0.190 +/- 0.03 versus 0.138 +/- 0.03 (P < 0.001) and D - 0.200 +/- 0.04 versus 0.152 +/- 0.03 (P < 0.001). No significant day-to-night differences were found in both groups. Steeper QT/RR slope and complete lack of day-to-night differences in VT/VF patients show inappropriate QT adaptation to the heart rate changes. The prognostic significance of this parameter needs prospective studies.

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

Effect of exercise, heat stress and dehydration on myocardial performance.

PubMed

Fehling, P C; Haller, J M; Lefferts, W K; Hultquist, E M; Wharton, M; Rowland, T W; Smith, D L

2015-06-01

Myocardial dysfunction is a well-documented outcome of extended periods of high cardiac output. Whether similar effects occur during firefighting, an occupation characterized by repeated periods of work compounded by dehydration and heat stress, is uncertain. To investigate the independent and combined effects of moderate heat stress and dehydration on indicators of myocardial performance following intermittent, submaximal treadmill exercise while wearing personal protective equipment (PPE). Twelve aerobically fit young men (age 21.5±2.6 years; maximal oxygen uptake [VO2max] 60.3±4.4ml kg(-1) min(-1)) performed intermittent treadmill walking exercise consisting of three 20min bouts at an intensity of ~40% VO2max separated by two periods of rest in four different conditions in random order: (i) no heat stress-euhydrated, (ii) heat stress-euhydrated (heat stress created by wearing PPE, (iii) no heat stress-dehydrated and (iv) heat stress-dehydrated. We measured core temperature by a telemetric gastrointestinal pill. We determined cardiac variables by standard echocardiographic techniques immediately before and ~30min after exercise. We recorded no significant changes in markers of systolic (ejection fraction, shortening fraction, tissue Doppler-S) or diastolic (mitral peak E velocity, tissue Doppler-E' and E/E') function following exercise in any of the four conditions. In this model of exercise designed to mimic the work, heat stress and dehydration associated with firefighting activities, we observed no negative effects on myocardial inotropic or lusitropic function. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

PubMed

Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

2016-01-01

limitations of these tests used and the sample sizes, olfactory dysfunction appears to be associated with the inability to identify odors reliably and consistently, not with the loss of an ability to identify specific odors. Irreproducibility in odor identification appears to be a non-disease-specific, general feature of olfactory dysfunction that is accelerated or accentuated in neurodegenerative disease. It may reflect a fundamental organizational principle of the olfactory system, which is more "error-prone" than other sensory systems.

Saturated high-fat diet-induced obesity increases adenylate cyclase of myocardial β-adrenergic system and does not compromise cardiac function.

PubMed

Vileigas, Danielle F; de Deus, Adriana F; da Silva, Danielle C T; de Tomasi, Loreta C; de Campos, Dijon H S; Adorni, Caroline S; de Oliveira, Scarlet M; Sant'Ana, Paula G; Okoshi, Katashi; Padovani, Carlos R; Cicogna, Antonio C

2016-09-01

Obesity is a worldwide pandemic associated with high incidence of cardiovascular disease. The mechanisms by which the obesity leads cardiac dysfunction are not fully elucidated and few studies have evaluated the relationship between obesity and proteins involved in myocardial β-adrenergic (βA) system. The purpose of this study was to evaluate the cardiac function and βA pathway components in myocardium of obese rats. Male Wistar rats were distributed into two groups: control (n = 17; standard diet) and obese (n = 17; saturated high-fat diet) fed for 33 weeks. Nutritional profile and comorbidities were assessed. Cardiac structure and function was evaluated by macroscopic postmortem, echocardiographic and isolated papillary muscle analyzes. Myocardial protein expression of β1- and β2-adrenergic receptors, Gαs protein, adenylate cyclase (AC) and protein kinase A (PKA) was performed by Western blot. Cardiac cyclic adenosine monophosphate (cAMP) levels and PKA activity were assessed by ELISA Obese rats showed increased adiposity index (P < 0.001) and several comorbidities as hypertension, glucose intolerance, insulin resistance, and dyslipidemia compared with control rats. Echocardiographic assessment revealed increased left atrium diameter (C: 4.98 ± 0.38 vs. Ob: 5.47 ± 0.53, P = 0.024) and posterior wall shortening velocity (C: 37.1 ± 3.6 vs. Ob: 41.8 ± 3.8, P = 0.007) in obese group. Papillary muscle evaluation indicated that baseline data and myocardial responsiveness to isoproterenol stimulation were similar between the groups. Protein expression of myocardial AC was higher in obese group than in the control (C: 1.00 ± 0.21 vs. Ob: 1.25 ± 0.10, P = 0.025), whereas the other components were unchanged. These results suggest that saturated high-fat diet-induced obesity was not effective in triggering cardiac dysfunction and impair the beta-adrenergic signaling. © 2016 The Authors. Physiological Reports published by Wiley

Beneficial effects of intracoronary nicorandil on microvascular dysfunction after primary percutaneous coronary intervention: demonstration of its superiority to nitroglycerin in a cross-over study.

PubMed

Ito, Noritoshi; Nanto, Shinsuke; Doi, Yasuji; Kurozumi, Yuma; Natsukawa, Tomoaki; Shibata, Hiroyuki; Morita, Masaya; Kawata, Atsushi; Tsuruoka, Ayumu; Sawano, Hirotaka; Okada, Ken-ichiro; Sakata, Yasuhiko; Kai, Tatsuro; Hayashi, Toru

2013-08-01

In patients undergoing primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI), coronary microvascular dysfunction is associated with poor prognosis. Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium (KATP) channels. The aim of this study was to clarify whether nicorandil, a hybrid KATP channel opener and nitric oxide donor, may be a good candidate for improving microvascular dysfunction even when administered after primary PCI. We compared the beneficial effects of nicorandil and nitroglycerin on microvascular function in 60 consecutive patients with STEMI. After primary PCI, all patients received single intracoronary administrations of nitroglycerin (250 μg) and nicorandil (2 mg) in a randomized order; 30 received nicorandil first, while the other 30 received nitroglycerin first. Microvascular dysfunction was evaluated with the index of microcirculatory resistance (IMR), defined as the distal coronary pressure multiplied by the hyperemic mean transit time. As a first administration, nicorandil decreased IMR significantly more than did nitroglycerin (median [interquartile ranges]: 10.8[5.2-20.7] U vs. 2.1[1.0-6.0] U, p=0.0002).As a second administration, nicorandil further decreased IMR, while nitroglycerin did not (median [interquartile ranges]: 6.0[1.3-12.7] U vs. -1.4[-2.6 to 1.3] U, p<0.0001). The IMR after the second administration was significantly associated with myocardial blush grade, angiographic TIMI frame count after the procedure, and peak creatine kinase level. Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.

The effect of captopril and losartan on the electrophysiology of myocardial cells of myocardial ischemia rats.

PubMed

Shi, Xiangmin; Shan, Zhaoling; Yuan, Hongtao; Guo, Hongyang; Wang, Yutang

2014-01-01

This study aims to investigate the effect of captopril and losartan on the electrophysiology of myocardial cells parameters in ventricular vulnerable period and effective refractory period of myocardial ischemia rats. 96 wistar rats were enrolled in the study and divided into six groups: Captopril myocardial ischemia group, losartan myocardial ischemia group, myocardial ischemia control group, captopril normal group, losartan normal group and normal control group (n=16). We observed morphological changes of myocardial tissue in each group. The cardiac electrophysiological parameters in effective refractory period of each group were measured. Creatine kinase (CK), alanine aminotransferase (GOT), lactate dehydrogenase (LDH), the expression of Cardiotrophin 1 (CT-1) and malonaldehyde (MDA) were detected. Compared the losartan and captopril group with the control group, (P<0.05). Losartan and captopril can shorten the ventricular vulnerable period of the normal group and ischemic group. There was no interaction effect between losartan and captopril group and the acute myocardial ischemia group. The effect of losartan and captopril on time window in ventricular vulnerable period showed that compared with the control group (P<0.05). Losartan and captopril had a significant effect on prolonged effective refractory period of normal and ischemic rats. There was no interaction effect between losartan and captopril group and the acute myocardial ischemia group. Compared with the myocardial ischemia control group, CK, GOT, LDH and MDA decreased in captopril and losartan myocardial ischemia groups (P<0.05). Losartan and captopril had a significant effect on prolonged effective refractory period and shorten ventricular vulnerable period, they can also effectively prevent arrhythmias.

Myocardialization of the cardiac outflow tract

NASA Technical Reports Server (NTRS)

van den Hoff, M. J.; Moorman, A. F.; Ruijter, J. M.; Lamers, W. H.; Bennington, R. W.; Markwald, R. R.; Wessels, A.

1999-01-01

During development, the single-circuited cardiac tube transforms into a double-circuited four-chambered heart by a complex process of remodeling, differential growth, and septation. In this process the endocardial cushion tissues of the atrioventricular junction and outflow tract (OFT) play a crucial role as they contribute to the mesenchymal components of the developing septa and valves in the developing heart. After fusion, the endocardial ridges in the proximal portion of the OFT initially form a mesenchymal outlet septum. In the adult heart, however, this outlet septum is basically a muscular structure. Hence, the mesenchyme of the proximal outlet septum has to be replaced by cardiomyocytes. We have dubbed this process "myocardialization." Our immunohistochemical analysis of staged chicken hearts demonstrates that myocardialization takes place by ingrowth of existing myocardium into the mesenchymal outlet septum. Compared to other events in cardiac septation, it is a relatively late process, being initialized around stage H/H28 and being basically completed around stage H/H38. To unravel the molecular mechanisms that are responsible for the induction and regulation of myocardialization, an in vitro culture system in which myocardialization could be mimicked and manipulated was developed. Using this in vitro myocardialization assay it was observed that under the standard culture conditions (i) whole OFT explants from stage H/H20 and younger did not spontaneously myocardialize the collagen matrix, (ii) explants from stage H/H21 and older spontaneously formed extensive myocardial networks, (iii) the myocardium of the OFT could be induced to myocardialize and was therefore "myocardialization-competent" at all stages tested (H/H16-30), (iv) myocardialization was induced by factors produced by, most likely, the nonmyocardial component of the outflow tract, (v) at none of the embryonic stages analyzed was ventricular myocardium myocardialization-competent, and finally

Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study.

PubMed

Vallabhajosyula, Saraschandra; Kumar, Mukesh; Pandompatam, Govind; Sakhuja, Ankit; Kashyap, Rahul; Kashani, Kianoush; Gajic, Ognjen; Geske, Jeffrey B; Jentzer, Jacob C

2017-09-07

Echocardiographic myocardial dysfunction is reported commonly in sepsis and septic shock, but there are limited data on sepsis-related right ventricular dysfunction. This study sought to evaluate the association of right ventricular dysfunction with clinical outcomes in patients with severe sepsis and septic shock. Historical cohort study of adult patients admitted to all intensive care units at the Mayo Clinic from January 1, 2007 through December 31, 2014 for severe sepsis and septic shock, who had an echocardiogram performed within 72 h of admission. Patients with prior heart failure, cor-pulmonale, pulmonary hypertension and valvular disease were excluded. Right ventricular dysfunction was defined by the American Society of Echocardiography criteria. Outcomes included 1-year survival, in-hospital mortality and length of stay. Right ventricular dysfunction was present in 214 (55%) of 388 patients who met the inclusion criteria-isolated right ventricular dysfunction was seen in 100 (47%) and combined right and left ventricular dysfunction in 114 (53%). The baseline characteristics were similar between cohorts except for the higher mechanical ventilation use in patients with isolated right ventricular dysfunction. Echocardiographic findings demonstrated lower right ventricular and tricuspid valve velocities in patients with right ventricular dysfunction and lower left ventricular ejection fraction and increased mitral E/e' ratios in patients with combined right and left ventricular dysfunction. After adjustment for age, comorbidity, illness severity, septic shock and use of mechanical ventilation, isolated right ventricular dysfunction was independently associated with worse 1-year survival-hazard ratio 1.6 [95% confidence interval 1.2-2.1; p = 0.002) in patients with sepsis and septic shock. Isolated right ventricular dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival.

Lisinopril. A review of its pharmacology and clinical efficacy in the early management of acute myocardial infarction.

PubMed

Goa, K L; Balfour, J A; Zuanetti, G

1996-10-01

Following establishment of its efficacy in hypertension and congestive heart failure, the ACE inhibitor lisinopril has now been shown to reduce mortality and cardiovascular morbidity in patients with myocardial infarction when administered as early treatment. The ability of lisinopril to attenuate the detrimental effects of left ventricular remodelling is a key mechanism; however, additional cardioprotective and vasculoprotective actions are postulated to play a role in mediating the early benefit. The GISSI-3 trial in > 19 000 patients has demonstrated that, when given orally within 24 hours of symptom onset and continued for 6 weeks, lisinopril (with or without nitrates) produces measurable survival benefits within 1 to 2 days of starting treatment. Compared with no lisinopril treatment, reductions of 11% in risk of mortality and 7.7% in a combined end-point (death plus severe left ventricular dysfunction) were evident at 6 weeks. Advantages were apparent in all types of patients. Thus, those at high risk-women, the elderly, patients with diabetes mellitus and those with anterior infarct and/or Killip class > 1 -also benefited. These gains in combined end-point events persisted in the longer term, despite treatment withdrawal after 6 weeks in most patients. At 6 months, the incidence rate for the combined end-point remained lower than with control (a 6.2% reduction). The GISSI-3 results concur with those from recent large investigations (ISIS-4, CCS-1, SMILE) of other ACE inhibitors as early management in myocardial infarction. However, the results of the CONSENSUS II trial (using intravenous enalaprilat then oral enalapril) were unfavourable in some patients. These findings, together with the development of persistent hypotension and, to a lesser extent, renal dysfunction among patients in the GISSI-3 trial, have prompted considerable debate over optimum treatment strategies. Present opinion generally holds that therapy with lisinopril or other ACE inhibitors

Pathophysiology of Cardiopulmonary Bypass: Current Strategies for the Prevention and Treatment of Anemia, Coagulopathy, and Organ Dysfunction.

PubMed

Esper, Stephen A; Subramaniam, Kathirvel; Tanaka, Kenichi A

2014-06-01

The techniques and equipment of cardiopulmonary bypass (CPB) have evolved over the past 60 years, and numerous numbers of cardiac surgical procedures are conducted around the world using CPB. Despite more widespread applications of percutaneous coronary and valvular interventions, the need for cardiac surgery using CPB remains the standard approach for certain cardiac pathologies because some patients are ineligible for percutaneous procedures, or such procedures are unsuccessful in some. The ageing patient population for cardiac surgery poses a number of clinical challenges, including anemia, decreased cardiopulmonary reserve, chronic antithrombotic therapy, neurocognitive dysfunction, and renal insufficiency. The use of CPB is associated with inductions of systemic inflammatory responses involving both cellular and humoral interactions. Inflammatory pathways are complex and redundant, and thus, the reactions can be profoundly amplified to produce a multiorgan dysfunction that can manifest as capillary leak syndrome, coagulopathy, respiratory failure, myocardial dysfunction, renal insufficiency, and neurocognitive decline. In this review, pathophysiological aspects of CPB are considered from a practical point of view, and preventive strategies for hemodilutional anemia, coagulopathy, inflammation, metabolic derangement, and neurocognitive and renal dysfunction are discussed. © The Author(s) 2014.

Effect of first myocardial ischemic event on renal function.

PubMed

Eijkelkamp, Wouter B A; de Graeff, Pieter A; van Veldhuisen, Dirk J; van Dokkum, Richard P E; Gansevoort, Ronald T; de Jong, Paul E; de Zeeuw, Dick; Hillege, Hans L

2007-07-01

Effects of cardiovascular dysfunction on renal function have been poorly characterized. Therefore, we investigated the relation between a first ischemic cardiac event and long-term renal function changes in the general population from the PREVEND study. We studied 6,360 subjects with a total follow-up duration of 27.017 subject-years. The estimated mean proportional increase in serum creatinine after a first ischemic cardiac event was 3.1% compared with 0.4% per year of follow-up in subjects without such an event (p = 0.005). This represented a significantly larger decrease in estimated glomerular filtration rate after the event in subjects with an event versus the decrease in subjects without a first ischemic cardiac event (2.2 vs 0.5 ml/min/1.73 m(2)/year of follow-up, p = 0.006). In multivariate analysis with adjustment for renal risk factors, this event showed an independent association with serum creatinine change. In conclusion, a first ischemic cardiac event appears to enhance the natural decrease in renal function. Because even mild renal dysfunction should be considered a major cardiovascular risk factor after myocardial infarction, increased renal function loss after an ischemic cardiac event could add to the risk for subsequent cardiovascular morbidity, thus closing a vicious circle.

Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction.

PubMed

Allijn, Iris E; Czarny, Bertrand M S; Wang, Xiaoyuan; Chong, Suet Yen; Weiler, Marek; da Silva, Acarilia Eduardo; Metselaar, Josbert M; Lam, Carolyn Su Ping; Pastorin, Giorgia; de Kleijn, Dominique P V; Storm, Gert; Wang, Jiong-Wei; Schiffelers, Raymond M

2017-02-10

Inflammation is a known mediator of adverse ventricular remodeling after myocardial infarction (MI) that may lead to reduction of ejection fraction and subsequent heart failure. Berberine is a isoquinoline quarternary alkaloid from plants that has been associated with anti-inflammatory, anti-oxidative, and cardioprotective properties. Its poor solubility in aqueous buffers and its short half-life in the circulation upon injection, however, have been hampering the extensive usage of this natural product. We hypothesized that encapsulation of berberine into long circulating liposomes could improve its therapeutic availability and efficacy by protecting cardiac function against MI in vivo. Berberine-loaded liposomes were prepared by ethanol injection and characterized. They contained 0.3mg/mL of the drug and were 0.11μm in diameter. Subsequently they were tested for IL-6 secretion inhibition in RAW 264.7 macrophages and for cardiac function protection against adverse remodeling after MI in C57BL/6J mice. In vitro, free berberine significantly inhibited IL-6 secretion (IC 50 =10.4μM), whereas encapsulated berberine did not as it was not released from the formulation in the time frame of the in vitro study. In vivo, berberine-loaded liposomes significantly preserved the cardiac ejection fraction at day 28 after MI by 64% as compared to control liposomes and free berberine. In conclusion, liposomal encapsulation enhanced the solubility of berberine in buffer and preserves ejection fraction after MI. This shows that delivery of berberine-loaded liposomes significantly improves its therapeutic availability and identifies berberine-loaded liposomes as potential treatment of adverse remodeling after MI. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of advanced echocardiography and cardiovascular magnetic resonance in the assessment of myocardial function in Marfan syndrome-An update.

PubMed

Kiotsekoglou, Anatoli; Moggridge, James C; Child, Anne H; Rask, Peter

2017-05-01

Cardiovascular assessment of patients with Marfan syndrome has normally focused on the aortic root and vascular manifestations of the disease due to the high risk of aortic dissection. Although primary myocardial impairment has long been suspected in these patients, the evidence has been controversial. Advanced echocardiography and cardiovascular magnetic resonance imaging have proven to be effective, accurate, and more sensitive in the detection of subtle cardiac dysfunction. The application of these techniques to Marfan syndrome over the last 10 years has made significant progress in demonstrating the presence of primary myocardial impairment in these patients, but further work is still required to obtain confirmatory molecular, pathophysiological, and prognostic clinical data. Phenotypic expression of the disease has prognostic value, also suggesting potential effective medical therapy. © 2017, Wiley Periodicals, Inc.

Panic attack triggering myocardial ischemia documented by myocardial perfusion imaging study. A case report

PubMed Central

2012-01-01

Background Chest pain, a key element in the investigation of coronary artery disease is often regarded as a benign prognosis when present in panic attacks. However, panic disorder has been suggested as an independent risk factor for long-term prognosis of cardiovascular diseases and a trigger of acute myocardial infarction. Objective Faced with the extreme importance in differentiate from ischemic to non-ischemic chest pain, we report a case of panic attack induced by inhalation of 35% carbon dioxide triggering myocardial ischemia, documented by myocardial perfusion imaging study. Discussion Panic attack is undoubtedly a strong component of mental stress. Patients with coronary artery disease may present myocardial ischemia in mental stress response by two ways: an increase in coronary vasomotor tone or a sympathetic hyperactivity leading to a rise in myocardial oxygen consumption. Coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. Possibly the carbon dioxide challenge test could trigger myocardial ischemia by the same mechanisms. Conclusion The use of mental stress has been suggested as an alternative method for myocardial ischemia investigation. Based on translational medicine objectives the use of CO2 challenge followed by Sestamibi SPECT could be a useful method to allow improved application of research-based knowledge to the medical field, specifically at the interface of PD and cardiovascular disease. PMID:22999016

Panic attack triggering myocardial ischemia documented by myocardial perfusion imaging study. A case report.

PubMed

Soares-Filho, Gastão Luiz Fonseca; Mesquita, Claudio Tinoco; Mesquita, Evandro Tinoco; Arias-Carrión, Oscar; Machado, Sergio; González, Manuel Menéndez; Valença, Alexandre Martins; Nardi, Antonio Egidio

2012-09-21

Chest pain, a key element in the investigation of coronary artery disease is often regarded as a benign prognosis when present in panic attacks. However, panic disorder has been suggested as an independent risk factor for long-term prognosis of cardiovascular diseases and a trigger of acute myocardial infarction. Faced with the extreme importance in differentiate from ischemic to non-ischemic chest pain, we report a case of panic attack induced by inhalation of 35% carbon dioxide triggering myocardial ischemia, documented by myocardial perfusion imaging study. Panic attack is undoubtedly a strong component of mental stress. Patients with coronary artery disease may present myocardial ischemia in mental stress response by two ways: an increase in coronary vasomotor tone or a sympathetic hyperactivity leading to a rise in myocardial oxygen consumption. Coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. Possibly the carbon dioxide challenge test could trigger myocardial ischemia by the same mechanisms. The use of mental stress has been suggested as an alternative method for myocardial ischemia investigation. Based on translational medicine objectives the use of CO2 challenge followed by Sestamibi SPECT could be a useful method to allow improved application of research-based knowledge to the medical field, specifically at the interface of PD and cardiovascular disease.

Stress Cardiac MRI in Women With Myocardial Infarction and Nonobstructive Coronary Artery Disease.

PubMed

Mauricio, Rina; Srichai, Monvadi B; Axel, Leon; Hochman, Judith S; Reynolds, Harmony R

2016-10-01

In a prospective study, cardiac MRI (CMR) and intravascular ultrasound were performed in women with myocardial infarction (MI) and nonobstructive coronary artery disease (MINOCA). Forty participants underwent adenosine-stress CMR (sCMR). Abnormal perfusion may co-localize with ischemic late gadolinium enhancement (LGE) and T2-weighted signal hyperintensity (T2+), suggesting microvascular dysfunction contributed to MI. Qualitative perfusion analysis was performed by 2 independent readers. Abnormal myocardial perfusion reserve index (MPRI) was defined as global average ≤1.84. Abnormal rest perfusion was present in 10 patients (25%) and stress perfusion abnormalities in 25 (63%). Abnormal stress perfusion was not associated with LGE but tended to occur with T2+. Among patients with abnormal perfusion and LGE, the LGE pattern was ischemic in half. The locations of abnormal perfusion and LGE matched in 75%, T2+ in 100%. Abnormal stress perfusion was not associated with plaque disruption and matched in location in 63%. MPRI was abnormal in 10 patients (25%) and was not associated with LGE, T2+ or plaque disruption. Abnormal perfusion on sCMR is common among women with MINOCA. Abnormal perfusion usually co-localized with LGE and/or T2+ when present. Variability in LGE pattern leads to uncertainty about whether the finding of abnormal perfusion was cause or consequence of the tissue state leading to LGE. Low MPRI, possibly indicating diffuse microvascular disease, was observed with and without LGE and T2+. Multiple mechanisms may lead to abnormal perfusion on sCMR. Microvascular dysfunction may contribute to the pathogenesis of and coexist with other causes of MINOCA. © 2016 Wiley Periodicals, Inc.

Endothelial dysfunction in patients with coronary atherosclerosis.

PubMed

Chapidze, L; Kapanadze, S; Dolidze, N; Bakhutashvili, Z; Latsabidze, N

2007-01-01

It is well known that endothelial dysfunction as a nontraditional risk factor is an important early event in the pathogenesis of coronary atherosclerosis, contributing to plaque initiation and progression. In order to assess endothelial function plasma nitric oxide (NO) concentrations were determined. A total of 157 patients (119 men and 38 women, mean age 57+/-5,4 years) with coronary atherosclerosis were enrolled in the research. The study was cross-sectional in design. Most of the patients (n=127) had undergone myocardial revascularization procedures. There was statistically significant difference in mean values of plasma nitric oxide levels between patients with coronary atherosclerosis and healthy subjects (11,1+/-2,52 mkmol/L and 22,3+/-3,27 mkmol/L, respectively. p<0,01). Among all 157 patients only 17% had normal NO concentrations. In 59% cases low and in 24% cases high nitric oxide levels were found. Extent of coronary artery disease was associated with severity of endothelial dysfunction. The patients with three-vessel disease had the lowest mean plasma NO concentration. There was statistically significant negative correlation between mean plasma NO level and extent of coronary artery disease. Measurement of plasma nitric oxide concentration will give useful information for cardiologists, modification of abnormal levels of this parameter may delay progression of aggressive atherosclerotic process and thus, may prevent recurrent coronary events in patients with coronary atherosclerosis.

Cardiac-specific knockout of ETA receptor mitigates low ambient temperature-induced cardiac hypertrophy and contractile dysfunction

PubMed Central

Zhang, Yingmei; Li, Linlin; Hua, Yinan; Nunn, Jennifer M.; Dong, Feng; Yanagisawa, Masashi; Ren, Jun

2012-01-01

Cold exposure is associated with oxidative stress and cardiac dysfunction. The endothelin (ET) system, which plays a key role in myocardial homeostasis, may participate in cold exposure-induced cardiovascular dysfunction. This study was designed to examine the role of ET-1 in cold stress-induced cardiac geometric and contractile responses. Wild-type (WT) and ETA receptor knockout (ETAKO) mice were assigned to normal or cold exposure (4°C) environment for 2 and 5 weeks prior to evaluation of cardiac geometry, contractile, and intracellular Ca2+ properties. Levels of the temperature sensor transient receptor potential vanilloid (TRPV1), mitochondrial proteins for biogenesis and oxidative phosphorylation, including UCP2, HSP90, and PGC1α were evaluated. Cold stress triggered cardiac hypertrophy, depressed myocardial contractile capacity, including fractional shortening, peak shortening, and maximal velocity of shortening/relengthening, reduced intracellular Ca2+ release, prolonged intracellular Ca2+ decay and relengthening duration, generation of ROS and superoxide, as well as apoptosis, the effects of which were blunted by ETAKO. Western blotting revealed downregulated TRPV1 and PGC1α as well as upregulated UCP2 and activation of GSK3β, GATA4, and CREB in cold-stressed WT mouse hearts, which were obliterated by ETAKO. Levels of HSP90, an essential regulator for thermotolerance, were unchanged. The TRPV1 agonist SA13353 attenuated whereas TRPV1 antagonist capsazepine mimicked cold stress- or ET-1-induced cardiac anomalies. The GSK3β inhibitor SB216763 ablated cold stress-induced cardiac contractile (but not remodeling) changes and ET-1-induced TRPV1 downregulation. These data suggest that ETAKO protects against cold exposure-induced cardiac remodeling and dysfunction mediated through TRPV1 and mitochondrial function. PMID:22442497

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

PubMed Central

Ferreira, João Pedro; Machu, Jean‐Loup; Girerd, Nicolas; Jaisser, Frederic; Thum, Thomas; Butler, Javed; González, Arantxa; Diez, Javier; Heymans, Stephane; McDonald, Kenneth; Gyöngyösi, Mariann; Firat, Hueseyin; Rossignol, Patrick; Pizard, Anne

2017-01-01

Abstract Aims Myocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European‐Commission‐funded ‘FIBROTARGETS’ is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti‐fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure. Methods and results The FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12 000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community‐based population cohorts, cardiovascular risk cohorts, and heart failure cohorts. Conclusions The FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific ‘fibrotic’ phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti‐fibrotic therapies for heart failure. PMID:28988439

Double valve replacement in a patient with implantable cardioverter defibrillator with severe left ventricular dysfunction.

PubMed

Manjunath, Girish; Rao, Prakash; Prakash, Nagendra; Shivaram, B K

2016-01-01

Recent data from landmark trials suggest that the indications for cardiac pacing and implantable cardioverter defibrillators (ICDs) are set to expand to include heart failure, sleep-disordered breathing, and possibly routine implantation in patients with myocardial infarction and poor ventricular function.[1] This will inevitably result in more patients with cardiac devices undergoing surgeries. Perioperative electromagnetic interference and their potential effects on ICDs pose considerable challenges to the anesthesiologists.[2] We present a case of a patient with automatic ICD with severe left ventricular dysfunction posted for double valve replacement.

The Predictive Role of Serum Triglyceride to High-Density Lipoprotein Cholesterol Ratio According to Renal Function in Patients with Acute Myocardial Infarction

PubMed Central

Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyoon; Moon, Joo Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2016-01-01

Objective A high serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic value of this ratio in patients with renal dysfunction is unclear. We examined the association of the TG/HDL-C ratio with major adverse cardiovascular events (MACEs) according to renal function in patients with acute myocardial infarction (AMI). Method This study was based on the Korea Acute Myocardial Infarction Registry database. Of 13,897 patients who were diagnosed with AMI, the study population included the 7,016 patients with available TG/HDL-C ratio data. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR), and the TG/HDL-C ratio was categorized into tertiles. We investigated 12-month MACEs, which included cardiac death, myocardial infarction, and repeated percutaneous coronary intervention or coronary artery bypass grafting. Results During the 12-month follow up period, 593 patients experienced MACEs. There was a significant association between the TG/HDL-C ratio and MACEs (p<0.001) in the entire study cohort. Having a TG/HDL-C ratio value in the highest tertile of TG/HDL-C ratio was an independent factor associated with increased risk of MACEs (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.26–1.93; p<0.001). Then we performed subgroup analyses according to renal function. In patients with normal renal function (eGFR ≥ 90 ml/min/1.73m2) and mild renal dysfunction (eGFR ≥ 60 to < 90ml/min/1.73m2), a higher TG/HDL-C ratio was significantly associated with increased risk of MACEs (HR, 1.64; 95% CI, 1.04–2.60; p = 0.035; and HR, 1.56; 95% CI, 1.14–2.12; p = 0.005, respectively). However, in patients with moderate renal dysfunction (eGFR < 60 ml/min/1.73m2), TG/HDL-C ratio lost its predictive value on the risk of MACEs (HR, 1.23; 95% CI, 0.82–1.83; p = 0.317). Conclusions In

The Predictive Role of Serum Triglyceride to High-Density Lipoprotein Cholesterol Ratio According to Renal Function in Patients with Acute Myocardial Infarction.

PubMed

Kim, Jin Sug; Kim, Weon; Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyoon; Moon, Joo Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2016-01-01

A high serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic value of this ratio in patients with renal dysfunction is unclear. We examined the association of the TG/HDL-C ratio with major adverse cardiovascular events (MACEs) according to renal function in patients with acute myocardial infarction (AMI). This study was based on the Korea Acute Myocardial Infarction Registry database. Of 13,897 patients who were diagnosed with AMI, the study population included the 7,016 patients with available TG/HDL-C ratio data. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR), and the TG/HDL-C ratio was categorized into tertiles. We investigated 12-month MACEs, which included cardiac death, myocardial infarction, and repeated percutaneous coronary intervention or coronary artery bypass grafting. During the 12-month follow up period, 593 patients experienced MACEs. There was a significant association between the TG/HDL-C ratio and MACEs (p<0.001) in the entire study cohort. Having a TG/HDL-C ratio value in the highest tertile of TG/HDL-C ratio was an independent factor associated with increased risk of MACEs (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.26-1.93; p<0.001). Then we performed subgroup analyses according to renal function. In patients with normal renal function (eGFR ≥ 90 ml/min/1.73m2) and mild renal dysfunction (eGFR ≥ 60 to < 90ml/min/1.73m2), a higher TG/HDL-C ratio was significantly associated with increased risk of MACEs (HR, 1.64; 95% CI, 1.04-2.60; p = 0.035; and HR, 1.56; 95% CI, 1.14-2.12; p = 0.005, respectively). However, in patients with moderate renal dysfunction (eGFR < 60 ml/min/1.73m2), TG/HDL-C ratio lost its predictive value on the risk of MACEs (HR, 1.23; 95% CI, 0.82-1.83; p = 0.317). In patients with AMI, TG/HDL-C ratio is a

Myocardial contusion following nonfatal blunt chest trauma

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

Kumar, S.A.; Puri, V.K.; Mittal, V.K.

1983-04-01

Currently available diagnostic techniques for myocardial contusion following blunt chest trauma were evaluated. We investigated 30 patients prospectively over a period of 1 year for the presence of myocardial contusion. Among the 30 patients, eight were found to have myocardial contusion on the basis of abnormal electrocardiograms, elevated creatine phosphokinase MB fraction (CPK-MB), and positive myocardial scan. Myocardial scan was positive in seven of eight patients (87.5%). CPK-MB fraction was elevated in four of eight patients (50%). Definitive electrocardiographic changes were seen in only two of eight patients (25%). It appears that myocardial scan using technetium pyrophosphate and CPK-MB fractionmore » determinations are the most reliable aids in diagnosis of myocardial contusion following blunt chest trauma.« less

Detecting Regional Myocardial Abnormalities in Patients With Wolff-Parkinson-White Syndrome With the Use of ECG-Gated Cardiac MDCT.

PubMed

Lee, Hye-Jeong; Uhm, Jae-Sun; Joung, Boyoung; Hong, Yoo Jin; Hur, Jin; Choi, Byoung Wook; Kim, Young Jin

2016-04-01

Myocardial dyskinesia caused by the accessory pathway and related reversible heart failure have been well documented in echocardiographic studies of pediatric patients with Wolff-Parkinson-White (WPW) syndrome. However, the long-term effects of dyskinesia on the myocardium of adult patients have not been studied in depth. The goal of the present study was to evaluate regional myocardial abnormalities on cardiac CT examinations of adult patients with WPW syndrome. Of 74 patients with WPW syndrome who underwent cardiac CT from January 2006 through December 2013, 58 patients (mean [± SD] age, 52.2 ± 12.7 years), 36 (62.1%) of whom were men, were included in the study after the presence of combined cardiac disease was excluded. Two observers blindly evaluated myocardial thickness and attenuation on cardiac CT scans. On the basis of CT findings, patients were classified as having either normal or abnormal findings. We compared the two groups for other clinical findings, including observations from ECG, echocardiography, and electrophysiologic study. Of the 58 patients studied, 16 patients (27.6%) were found to have myocardial abnormalities (i.e., abnormal wall thinning with or without low attenuation). All abnormal findings corresponded with the location of the accessory pathway. Patients with abnormal findings had statistically significantly decreased left ventricular function, compared with patients with normal findings (p < 0.001). The frequency of regional wall motion abnormality was statistically significantly higher in patients with abnormal findings (p = 0.043). However, echocardiography documented structurally normal hearts in all patients. A relatively high frequency (27.6%) of regional myocardial abnormalities was observed on the cardiac CT examinations of adult patients with WPW syndrome. These abnormal findings might reflect the long-term effects of dyskinesia, suggesting irreversible myocardial injury that ultimately causes left ventricular dysfunction.

SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

PubMed

Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing

2016-01-01

Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

Effects of atrial fibrillation on myocardial washout rate of thallium-201 on myocardial perfusion single-photon emission computed tomography.

PubMed

Kurisu, Satoshi; Nitta, Kazuhiro; Sumimoto, Yoji; Ikenaga, Hiroki; Ishibashi, Ken; Fukuda, Yukihiro; Kihara, Yasuki

2018-04-20

Myocardial perfusion single-photon emission computed tomography (SPECT) with thallium (Tl)-201 is an established modality for evaluating myocardial ischemia. We assessed the effects of atrial fibrillation (AF) on the myocardial washout rate (WR) of Tl-201 on myocardial perfusion SPECT. A total of 231 patients with no evidence of myocardial ischemia were enrolled retrospectively in this study. Patients were divided into two groups on the basis of the ECG at the time of myocardial perfusion SPECT. The mean myocardial WR of Tl-201 was calculated from the stress and the redistribution Bull's eye maps. There were 34 patients with AF and 197 patients with sinus rhythm. There were no significant differences in clinical variables, except for older age and higher heart rate in patients with AF. Myocardial WR of Tl-201 was significantly lower in patients with AF than those with sinus rhythm (46±12 vs. 51±8%, P=0.03). Multivariate analysis including these factors showed that female sex (β=0.18, P=0.02), AF (β=-0.14 P=0.03), hemoglobin (β=-0.18, P<0.01), and serum creatinine (β=0.24, P<0.01) were determinants of myocardial WR of Tl-201. Our data suggest that AF is associated with reduced myocardial WR of Tl-201 on myocardial perfuison SPECT.

PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

PubMed Central

Knight, Walter E.; Chen, Si; Zhang, Yishuai; Oikawa, Masayoshi; Wu, Meiping; Zhou, Qian; Miller, Clint L.; Cai, Yujun; Mickelsen, Deanne M.; Moravec, Christine; Small, Eric M.; Abe, Junichi; Yan, Chen

2016-01-01

Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β–stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance. PMID:27791092

Hemodynamic Profiles of Functional and Dysfunctional Forms of Repetitive Thinking.

PubMed

Ottaviani, Cristina; Brosschot, Jos F; Lonigro, Antonia; Medea, Barbara; Van Diest, Ilse; Thayer, Julian F

2017-04-01

The ability of the human brain to escape the here and now (mind wandering) can take functional (problem solving) and dysfunctional (perseverative cognition) routes. Although it has been proposed that only the latter may act as a mediator of the relationship between stress and cardiovascular disease, both functional and dysfunctional forms of repetitive thinking have been associated with blood pressure (BP) reactivity of the same magnitude. However, a similar BP reactivity may be caused by different physiological determinants, which may differ in their risk for cardiovascular pathology. To examine the way (hemodynamic profile) and the extent (compensation deficit) to which total peripheral resistance and cardiac output compensate for each other in determining BP reactivity during functional and dysfunctional types of repetitive thinking. Fifty-six healthy participants randomly underwent a perseverative cognition, a mind wandering, and a problem solving induction, each followed by a 5-min recovery period while their cardiovascular parameters were continuously monitored. Perseverative cognition and problem solving (but not mind wandering) elicited BP increases of similar magnitude. However, perseverative cognition was characterized by a more vascular (versus myocardial) profile compared to mind wandering and problem solving. As a consequence, BP recovery was impaired after perseverative cognition compared to the other two conditions. Given that high vascular resistance and delayed recovery are the hallmarks of hypertension the results suggest a potential mechanism through which perseverative cognition may act as a mediator in the relationship between stress and risk for developing precursors to cardiovascular disease.

Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition

PubMed Central

Fabiansen, Christian; Lykke, Mikkel; Hother, Anne-Louise; Koch, Jørgen; Nielsen, Ole Bækgaard; Hunter, Ingrid; Goetze, Jens P.; Friis, Henrik; Thymann, Thomas

2015-01-01

Background Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. Objective To determine malnutrition-induced echocardiographic disturbances and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. Methods and Results Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet (AGE-REF, n = 12) for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8). Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased markedly in MAIZE relative to AGE-REF during week 5–7 (p≤0.001). There was overall no difference in plasma cardiac troponin-T between groups. However, further analysis revealed that release of cardiac troponin-T in plasma was more frequent in AGE-REF compared with MAIZE (OR: 4.8; 95%CI: 1.2–19.7; p = 0.03). However, when release occurred, cardiac troponin-T concentration was 6.9-fold higher (95%CI: 3.0–15.9; p<0.001) in MAIZE compared to AGE-REF. At week 7, the mean body weight in MAIZE was lower than AGE-REF (8.3 vs 32.4 kg, p<0.001), whereas heart-weight relative to body-weight was similar across the three groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (p<0.001) and 27% higher in MAIZE vs WEIGHT-REF (p = 0.025). Conclusions Malnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide and it associates with cardiac injury by elevated cardiac troponin-T. Clinical studies are needed to see if the same applies for children suffering from

Multiple coronary stenting negatively affects myocardial recovery after coronary bypass grafting.

PubMed

Yajima, Shin; Yoshioka, Daisuke; Fukushima, Satsuki; Toda, Koichi; Miyagawa, Shigeru; Yoshikawa, Yasushi; Hata, Hiroki; Saito, Shunsuke; Domae, Keitaro; Sawa, Yoshiki

2018-05-14

We aimed to elucidate the relationship between the magnitude of myocardial recovery after coronary artery bypass grafting (CABG) and the prognosis and to explore the predictors of myocardial non-recovery. Eighty-one patients with a preoperative left ventricular ejection fraction (LVEF) ≤ 40% who underwent isolated CABG between 2002 and 2015 and had undergone echocardiographic follow-up (median follow-up, 3.1 years; interquartile range 1.2-6.0 years) were analyzed. The Recovery group comprised patients with LVEF improvement ≥ 10%, whereas the Non-recovery group comprised those with an LVEF improvement < 10%. Group differences in overall survival, freedom from major adverse cardiac events (MACEs), and readmission due to heart failure were evaluated. In addition, the risk factors for LVEF non-recovery were evaluated in a multivariate analysis. A total of 39 patients (48%) were in the Recovery group, whereas 42 patients (52%) were in the Non-recovery group. Although the survival and freedom from MACE rates were comparable, the rate of freedom from heart failure requiring hospitalization at 1, 5, and 8 years of follow-up was significantly lower in the Non-recovery group than in the Recovery group (p = 0.012). A history of percutaneous coronary intervention (PCI) was an exclusive independent risk factor for post-CABG myocardial non-recovery (odds ratio, 16.0; 95% confidence interval, 3.44-125). Furthermore, the number of coronary stents was negatively correlated with LVEF recovery (r = - 0.460, p = 0.024). Great consideration should be taken when performing CABG in patients with left ventricular dysfunction and a history of PCI, particularly in those with multiple coronary stents.

Cats with diabetes mellitus have diastolic dysfunction in the absence of structural heart disease.

PubMed

Pereira, N J; Novo Matos, J; Baron Toaldo, M; Bartoszuk, U; Summerfield, N; Riederer, A; Reusch, C; Glaus, T M

2017-07-01

Diabetes mellitus (DM) can result in cardiovascular dysfunction and heart failure characterized by diastolic dysfunction with or without the presence of systolic dysfunction in people and laboratory animals. The objective of this prospective study was to determine if cats with newly diagnosed DM had myocardial dysfunction and, if present, whether it would progress if appropriate antidiabetic therapy was commenced. Thirty-two diabetic cats were enrolled and received baseline echocardiographic examination; of these, 15 cats were re-examined after 6 months. Ten healthy age- and weight-matched cats served as controls. Diabetic cats at diagnosis showed decreased diastolic, but not systolic function, when compared to healthy controls, with lower mitral inflow E wave (E) and E/E' than controls. After 6 months, E and E/IVRT' decreased further in diabetic cats compared to the baseline evaluation. After excluding cats whose DM was in remission at 6 months, insulin-dependent diabetic cats had lower E, E/A and E' than controls. When classifying diastolic function according to E/A and E'/A', there was shift towards impaired relaxation patterns at 6 months. All insulin-dependent diabetic cats at 6 months had abnormal diastolic function. These results indicate that DM has similar effects on diastolic function in feline and human diabetics. The dysfunction seemed to progress rather than to normalize after 6 months, despite antidiabetic therapy. In cats with pre-existing heart disease, the development of DM could represent an important additional health risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Air Pollution-Induced Vascular Dysfunction: Potential Role of Endothelin-1 (ET-1) System

PubMed Central

Finch, Jordan; Conklin, Daniel J.

2015-01-01

Exposure to air pollution negatively impacts cardiovascular health. Studies show that increased exposure to a number of airborne pollutants increases the risk for cardiovascular disease progression, myocardial events, and cardiovascular mortality. A hypothesized mechanism linking air pollution and cardiovascular disease is the development of systemic inflammation and endothelium dysfunction, the latter of which can result from an imbalance of vasoactive factors within the vasculature. Endothelin-1 (ET-1) is a potent peptide vasoconstrictor that plays a significant role in regulating vascular homeostasis. It has been reported that the production and function of ET-1 and its receptors are upregulated in a number of disease states associated with endothelium dysfunction including hypertension and atherosclerosis. This mini-review surveys epidemiological and experimental air pollution studies focused on ET-1 dysregulation as a plausible mechanism underlying the development of cardiovascular disease. Although alterations in ET-1 system components are observed in some studies, there remains a need for future research to clarify whether these specific changes are compensatory or causally related to vascular injury and dysfunction. Moreover, further research may test the efficacy of selective ET-1 pharmacological interventions (e.g., ETA receptor inhibitors) to determine whether these treatments could impede the deleterious impact of air pollution exposure on cardiovascular health. PMID:26148452

Air Pollution-Induced Vascular Dysfunction: Potential Role of Endothelin-1 (ET-1) System.

PubMed

Finch, Jordan; Conklin, Daniel J

2016-07-01

Exposure to air pollution negatively impacts cardiovascular health. Studies show that increased exposure to a number of airborne pollutants increases the risk for cardiovascular disease progression, myocardial events, and cardiovascular mortality. A hypothesized mechanism linking air pollution and cardiovascular disease is the development of systemic inflammation and endothelium dysfunction, the latter of which can result from an imbalance of vasoactive factors within the vasculature. Endothelin-1 (ET-1) is a potent peptide vasoconstrictor that plays a significant role in regulating vascular homeostasis. It has been reported that the production and function of ET-1 and its receptors are upregulated in a number of disease states associated with endothelium dysfunction including hypertension and atherosclerosis. This mini-review surveys epidemiological and experimental air pollution studies focused on ET-1 dysregulation as a plausible mechanism underlying the development of cardiovascular disease. Although alterations in ET-1 system components are observed in some studies, there remains a need for future research to clarify whether these specific changes are compensatory or causally related to vascular injury and dysfunction. Moreover, further research may test the efficacy of selective ET-1 pharmacological interventions (e.g., ETA receptor inhibitors) to determine whether these treatments could impede the deleterious impact of air pollution exposure on cardiovascular health.

Respiratory physiotherapy in the pre and postoperative myocardial revascularization surgery.

PubMed

Cavenaghi, Simone; Ferreira, Lucas Lima; Marino, Lais Helena Carvalho; Lamari, Neuseli Marino

2011-01-01

The cardiovascular diseases are among the main death causes in the developed world. They have been increasing epidemically in the developing countries. In spite of several alternatives for the treatment of the coronary artery disease; the surgery of the myocardial revascularization is an option with proper indications of medium and long-term with good results. It provides the remission of the angina symptoms contributing to the increase of the expectation and improvement of the life quality. Most of patients undergoing myocardial revascularization surgery develop postoperative lung dysfunction with important reduction of the lung volumes, damages in the respiratory mechanism, decrease in the lung indulgence and increase of the respiratory work. The reduction of volumes and lung capacities can contribute to alterations in the gas exchanges, resulting in hypoxemia and decrease in the diffusion capacity. Taking this into account, the Physiotherapy has been requested more and more to perform in the pre as well as in the postoperative period of this surgery. This study aimed at updating the knowledge regarding the respiratory physiotherapy performance in the pre and postoperative period of the myocardial revascularization surgery enhancing the prevention of lung complications. The Physiotherapy uses several techniques in the preoperative period; such as: the incentive spirometry, exercises of deep breathing, cough, inspiratory muscle training, earlier ambulation and physiotherapeutic orientations. While in the postoperative period, the objective is the treatment after lung complications took place, performed by means of physiotherapeutic maneuvers and noninvasive respiratory devices, aiming at improving the respiratory mechanism, the lung reexpansion and the bronchial hygiene. Respiratory physiotherapy is an integral part in the care management of the patient with cardiopathy, either in the pre or in the postoperative period, since it contributes significantly to a

Impact of rosiglitazone and glyburide on nitrosative stress and myocardial blood flow regulation in type 2 diabetes mellitus.

PubMed

Pop-Busui, Rodica; Oral, Elif; Raffel, David; Byun, Jaeman; Bajirovic, Valida; Vivekanandan-Giri, Anuradha; Kellogg, Aaron; Pennathur, Subramaniam; Stevens, Martin J

2009-07-01

Cardiovascular disease, the leading cause of death in patients with type 2 diabetes mellitus (T2DM), is usually preceded by endothelial dysfunction and altered myocardial blood flow (MBF) regulation. Hyperglycemia, oxidative-nitrosative stress, systemic inflammation, and insulin resistance are implicated in the pathogenesis of abnormal MBF regulation, myocardial ischemia, and apoptosis. However, the impact of oral antihyperglycemic therapy on myocardial perfusion is controversial. Our objective was to explore the effect of rosiglitazone and glyburide on nitrosative stress and MBF regulation in subjects with T2DM. [(13)N]ammonia positron emission tomography and cold pressor testing were used in 27 diabetic subjects (mean age, 49 +/- 11 years; glycohemoglobin, 7% +/- 1.5%) randomized to either rosiglitazone 8 mg/d or glyburide 10 mg/d for 6 months. Isotope dilution gas chromatography-mass spectrometry was used to quantify plasma 3-nitrotyrosine, a stable marker of reactive nitrogen species. At 6 months, there were no significant differences between groups in the mean glycohemoglobin, blood pressure, or plasma lipids. Rosiglitazone significantly reduced plasma nitrotyrosine, high-sensitivity C-reactive protein, and von Willebrand antigen (P < .03 for all) and significantly increased plasma adiponectin (P < .05). No significant changes in these parameters were observed with glyburide. Treatment with glyburide, but not rosiglitazone, resulted in a significant deterioration in both resting and stress MBF. Rosiglitazone, but not glyburide, ameliorated markers of nitrosative stress and inflammation in subjects with T2DM without impairing myocardial perfusion.

Exercise-induced changes in mitral regurgitation in patients with prior myocardial infarction and left ventricular dysfunction: relation to mitral deformation and left ventricular function and shape.

PubMed

Giga, Vojislav; Ostojic, Miodrag; Vujisic-Tesic, Bosiljka; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Beleslin, Branko; Petrovic, Milan; Nedeljkovic, Milan; Nedeljkovic, Ivana; Milic, Natasa

2005-09-01

The aim of this study was to assess the relationship between exercise-induced changes in mitral regurgitation (MR) and echocardiographic characteristics of mitral deformation, global left ventricular (LV) function and shape at rest and after exercise. Forty consecutive patients with ischaemic MR due to prior myocardial infarction (MI), ejection fraction <45% in sinus rhythm underwent exercise-echocardiographic testing. Exercise-induced changes in effective regurgitant orifice (ERO) were compared with baseline and exercise-induced changes in mitral deformation and global LV function and shape. There was significant correlation between exercise-induced changes in ERO and changes in coaptation distance (r=0.80, P<0.0001), tenting area (r=0.79, P<0.0001) and mitral annular diameter (r=0.65, P<0.0001), as well as in end-systolic sphericity index (r=-0.50, P=0.001, respectively), and wall motion score index (r=0.44, P=0.004). In contrast, exercise-induced changes in ERO were not related to the echocardiographic features at rest. By stepwise multiple regression model, the exercise-induced changes in mitral deformation were found to independently correlate with exercise-induced changes in ERO (generalized r(2)=0.80, P<0.0001). Exercise-induced changes in severity of ischaemic MR in patients with LV dysfunction due to prior MI were independently related to changes in mitral deformation.

Relation between aortic knob width and subclinical left ventricular dysfunction in hypertensive patients.

PubMed

Gürbak, İsmail; Yıldız, İbrahim; Panç, Cafer

2018-01-29

The assessment of left ventricular (LV) structure and function is important in the evaluation of hypertensive heart disease, as it provides information on the cardiovascular morbidity and mortality. Aortic knob width (AKW) is a measurement of radiographic structure formed by the foreshortened aortic arch and a portion of the descending aorta. The main aim of this study was to investigate the relation between AKW on the routine chest radiography and subclinical LV dysfunction in hypertensive patients. A total of 144 patients with hypertension admitted to the cardiology outpatients clinic were enrolled consecutively. The patients were divided into two groups according to tissue Doppler-derived myocardial performance index (MPI): subclinical LV dysfunction group (abnormal MPI ≥ 0.5, n = 85) and absence of subclinical LV dysfunction group (normal MPI< 0.5, n = 59). Patients with subclinical LV dysfunction were older (60 ± 8 vs. 54 ± 8, p = 0.001). Left ventricular mass index (LVMI) (96 ± 27 vs. 74 ± 24, p < 0.001) and prevalence of LV hypertrophy (28 vs. 8%, p = 0.011) were significantly different between two groups. Patients with subclinical LV dysfunction had higher AKW (42 ± 6 vs. 34 ± 5, p < 0.001) compared with patients without subclinical LV dysfunction. There was a significant correlation between MPI and AKW (r = 0.7, p < 0.001). Multiple logistic regression analysis showed that AKW (β = 0.617, p = 0.001) and posterior wall thickness (PWth) (β = 1.189, p = 0.021) were independently associated with subclinical LV dysfunction. Analysis using the Receiver Operating Characteristic (ROC) curve has demonstrated that aortic knob of 37 mm constitutes the cutoff value for the presence of subclinical LV dysfunction with 85.9% sensitivity and 86.4% specificity (The Area under the Curve ± Standard Error (AUC±SE) = 0.916 ± 0.024, p < 0.001). AKW may provide important predictive information on subclinical LV dysfunction

Risk factors and outcomes of sepsis-induced myocardial dysfunction and stress-induced cardiomyopathy in sepsis or septic shock

PubMed Central

Jeong, Han Saem; Lee, Tae Hyub; Bang, Cho Hee; Kim, Jong-Ho; Hong, Soon Jun

2018-01-01

Abstract While both sepsis-induced myocardial dysfunction (SIMD) and stress-induced cardiomyopathy (SICMP) are common in patients with sepsis, the pathogenesis of the 2 diseases is different, and they require different treatment strategies. Thus, we aimed to investigate risk factors and outcomes between the 2 diseases. This retrospective study enrolled patients diagnosed with sepsis or septic shock, admitted to intensive care unit via emergency department in Korea University Anam Hospital, and who underwent transthoracic echocardiography within the first 24 hours of admission. In all, 25 patients with SIMD and 27 patients with SICMP were enrolled. Chronic obstructive pulmonary disease and a history of heart failure (HF) were more prevalent in both the SIMD and SICMP groups than in the control group. In the SIMD and SICMP groups, levels of inflammatory cytokines were similar. Serum troponin level was significantly elevated in the SICMP and SIMD group compared to the control group. N-terminal pro-brain natriuretic peptide (NT pro-BNP) level was significantly elevated in the SIMD group compared to the SICMP group or control group. The in-hospital mortality rate in the SIMD and SICMP group was about 40%, showing increased trends compared with the control group. The in-hospital mortality rate was significantly increased in SIMD group with EF<30% than in SICMP group with EF<30%. In multiple logistic regression analysis, a past history of diabetes mellitus (DM) and HF was significantly associated with the incidence of SIMD. Younger age, elevated levels of NT pro-BNP, and positive result of blood culture also showed significant odds ratio regard to the occurrence of SIMD. However, only elevated lactate and troponin level were positively associated with the incidence of SICMP. The SIMD and SICMP had different risk factors. The risk factors of SIMD were younger age, history of DM, history of HF, elevated NT pro-BNP, and positive result of blood culture. The elevated levels

PreSERVE-AMI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients With Left Ventricular Dysfunction Post STEMI.

PubMed

Quyyumi, Arshed A; Vasquez, Alejandro; Kereiakes, Dean J; Klapholz, Marc; Schaer, Gary L; Abdel-Latif, Ahmed; Frohwein, Stephen; Henry, Timothy D; Schatz, Richard A; Dib, Nabil; Toma, Catalin; Davidson, Charles J; Barsness, Gregory W; Shavelle, David M; Cohen, Martin; Poole, Joseph; Moss, Thomas; Hyde, Pamela; Kanakaraj, Anna Maria; Druker, Vitaly; Chung, Amy; Junge, Candice; Preti, Robert A; Smith, Robin L; Mazzo, David J; Pecora, Andrew; Losordo, Douglas W

2017-01-20

Despite direct immediate intervention and therapy, ST-segment-elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months (P<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose-dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (P=0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01495364. © 2016 American Heart Association, Inc.

Early Treatment With Zofenopril and Ramipril in Combination With Acetyl Salicylic Acid in Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: Results of a 5-Year Follow-up of Patients of the SMILE-4 Study.

PubMed

Borghi, Claudio; Omboni, Stefano; Novo, Salvatore; Vinereanu, Dragos; Ambrosio, Giuseppe; Ambrosioni, Ettore

2017-05-01

The SMILE-4 study showed that in patients with left ventricular dysfunction (LVD) after acute myocardial infarction, early treatment with zofenopril plus acetyl salicylic acid is associated with an improved 1-year survival, free from death or hospitalization for cardiovascular (CV) causes, as compared to ramipril plus acetyl salicylic acid. We now report CV outcomes during a 5-year follow-up of the patients of the SMILE-4 study. Three hundred eighty-six of the 518 patients completing the study (51.2%) could be tracked after the study end and 265 could be included in the analysis. During the 5.5 (±2.1) years of follow-up, the primary endpoint occurred in 27.8% of patients originally randomized and treated with zofenopril and in 43.8% of patients treated with ramipril [odds ratio (OR) and 95% confidence interval, 0.65 (0.43-0.98), P = 0.041]. Such a result was achieved through a significantly larger reduction in CV hospitalization under zofenopril [OR: 0.61 (0.37-0.99), P = 0.047], whereas reduction in mortality rate with zofenopril did not achieve statistical significance versus ramipril [OR: 0.75 (0.36-1.59), P = 0.459]. These results were in line with those achieved during the initial 1-year follow-up. Benefits of early treatment of patients with LVD after acute myocardial infarction with zofenopril are sustained over many years as compared to ramipril.

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.

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

Measurement of myocardial perfusion and infarction size using computer-aided diagnosis system for myocardial contrast echocardiography.

PubMed

Du, Guo-Qing; Xue, Jing-Yi; Guo, Yanhui; Chen, Shuang; Du, Pei; Wu, Yan; Wang, Yu-Hang; Zong, Li-Qiu; Tian, Jia-Wei

2015-09-01

Proper evaluation of myocardial microvascular perfusion and assessment of infarct size is critical for clinicians. We have developed a novel computer-aided diagnosis (CAD) approach for myocardial contrast echocardiography (MCE) to measure myocardial perfusion and infarct size. Rabbits underwent 15 min of coronary occlusion followed by reperfusion (group I, n = 15) or 60 min of coronary occlusion followed by reperfusion (group II, n = 15). Myocardial contrast echocardiography was performed before and 7 d after ischemia/reperfusion, and images were analyzed with the CAD system on the basis of eliminating particle swarm optimization clustering analysis. The myocardium was quickly and accurately detected using contrast-enhanced images, myocardial perfusion was quantitatively calibrated and a color-coded map calibrated by contrast intensity and automatically produced by the CAD system was used to outline the infarction region. Calibrated contrast intensity was significantly lower in infarct regions than in non-infarct regions, allowing differentiation of abnormal and normal myocardial perfusion. Receiver operating characteristic curve analysis documented that -54-pixel contrast intensity was an optimal cutoff point for the identification of infarcted myocardium with a sensitivity of 95.45% and specificity of 87.50%. Infarct sizes obtained using myocardial perfusion defect analysis of original contrast images and the contrast intensity-based color-coded map in computerized images were compared with infarct sizes measured using triphenyltetrazolium chloride staining. Use of the proposed CAD approach provided observers with more information. The infarct sizes obtained with myocardial perfusion defect analysis, the contrast intensity-based color-coded map and triphenyltetrazolium chloride staining were 23.72 ± 8.41%, 21.77 ± 7.8% and 18.21 ± 4.40% (% left ventricle) respectively (p > 0.05), indicating that computerized myocardial contrast echocardiography can

Impact of initial 24-h urine output on short-term outcomes in patients with ST-segment elevation myocardial infarction admitted without cardiogenic shock and renal dysfunction.

PubMed

Huang, Bi; Yang, Yanmin; Zhu, Jun; Liang, Yan; Tan, Huiqiong; Yu, Litian; Gao, Xin; Li, Jiandong; Zhang, Han; Wang, Juan; Wan, Huaibin

2015-05-01

Our study aims to evaluate the prognostic value of initial 24-h urine output (UO) in patients with ST-segment elevation myocardial infarction (STEMI) admitted without cardiogenic shock and renal dysfunction, and to determine the additional risk stratification offered by adding initial 24-h UO to TIMI risk score (TRS). Data from 7078 consecutive STEMI patients in a multi-center registry were retrospectively analyzed. Patients were divided into 4 groups according to initial 24-h UO quartiles. The primary endpoints were 7- and 30-day all-cause mortality. Patients in the lowest UO quartile (≤1020 mL) had significantly higher 7- and 30-day all-cause mortality rates, cardiogenic shock, and major adverse cardiovascular events (MACE) than those in other groups (all P<0.05). After multivariate adjustment, initial 24-h UO≤1020 mL was independently associated with an increased risk in 7-day all-cause mortality (HR=4.649, 95%CI 3.348-6.455) and 30-day all-cause mortality (HR=3.775, 95%CI 2.891-4.931) as well as 7-day MACE (HR=1.845, 95%CI 1.563-2.179) and 30-day MACE (HR=1.818, 95%CI 1.553-2.127). Initial 24-h UO provided additional risk stratification across all TRS groups and improved the discriminatory ability of TRS with respect to 7-day all-cause mortality (c-statistic from 0.704 to 0.764) and 30-day all-cause mortality (c-statistic from 0.706 to 0.743). Reduced initial 24-h UO (≤1020 mL) was associated with an increased risk in 7- and 30-day all-cause mortality and MACE in STEMI patients admitted without cardiogenic shock and renal dysfunction. The combination of initial 24-h UO and TRS improved short-term outcome prediction when compared to TRS alone, particularly in patients with initial 24-h UO≤1020 mL. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Post-infarct sleep disruption and its relation to cardiac remodeling in a rat model of myocardial infarction.

PubMed

Aghajani, Marjan; Faghihi, Mahdieh; Imani, Alireza; Vaez Mahdavi, Mohammad Reza; Shakoori, Abbas; Rastegar, Tayebeh; Parsa, Hoda; Mehrabi, Saman; Moradi, Fatemeh; Kazemi Moghaddam, Ehsan

2017-01-01

Sleep disruption after myocardial infarction (MI) by affecting ubiquitin-proteasome system (UPS) is thought to contribute to myocardial remodeling and progressive worsening of cardiac function. The aim of current study was to test the hypothesis about the increased risk of developing heart failure due to experience of sleep restriction (SR) after MI. Male Wistar rats (n = 40) were randomly assigned to four experimental groups: (1) Sham, (2) MI, (3) MI and SR (MI + SR) (4) Sham and SR (Sham + SR). MI was induced by permanent ligation of left anterior descending coronary artery. Twenty-four hours after surgery, animals were subjected to chronic SR paradigm. Blood sampling was performed at days 1, 8 and 21 after MI for determination of serum levels of creatine kinase-MB (CK-MB), corticosterone, malondialdehyde (MDA) and nitric oxide (NO). Finally, at 21 days after MI, echocardiographic parameters and expression of MuRF1, MaFBx, A20, eNOS, iNOS and NF-kB in the heart were evaluated. We used H&E staining to detect myocardial hypertrophy. We found out that post infarct SR increased corticosterone levels. Our results highlighted deteriorating effects of post-MI SR on NO production, oxidative stress, and echocardiographic indexes (p < 0.05). Moreover, its detrimental effects on myocardial damage were confirmed by overexpression of MuRF1, MaFBx, iNOS and NF-kB (p < 0.001) in left ventricle and downregulation of A20 and eNOS (p < 0.05). Furthermore, histological examination revealed that experience of SR after MI increased myocardial diameter as compared to Sham subjects (p < 0.05). Our data suggest that SR after MI leads to an enlargement of the heart within 21 days, marked by an increase in oxidative stress and NO production as well as an imbalance in UPS that ultimately results in cardiac dysfunction and heart failure.

Myocardial diseases of animals.

PubMed Central

Van Vleet, J. F.; Ferrans, V. J.

1986-01-01

In this review we have attempted a comprehensive compilation of the cardiac morphologic changes that occur in spontaneous and experimental myocardial diseases of animals. Our coverage addresses diseases of mammals and birds and includes these diseases found in both domesticated and wild animals. A similar review of the myocardial diseases in this broad range of animal species has not been attempted previously. We have summarized and illustrated the gross, microscopic, and ultrastructural alterations for these myocardial diseases; and, whenever possible, we have reviewed their biochemical pathogenesis. We have arranged the myocardial diseases for presentation and discussion according to an etiologic classification with seven categories. These include a group of idiopathic or primary cardiomyopathies recognized in man (hypertrophic, dilated, and restrictive types) and a large group of secondary cardiomyopathies with known causes, such as inherited tendency; nutritional deficiency; toxicity; physical injury and shock; endocrine disorders, and myocarditides of viral, bacterial, and protozoal causation. Considerable overlap exists between each of the etiologic groups in the spectrum of pathologic alterations seen in the myocardium. These include various degenerative changes, myocyte necrosis, and inflammatory lesions. However, some diseases show rather characteristic myocardial alterations such as vacuolar degeneration in anthracycline cardiotoxicity, myofibrillar lysis in furazolidone cardiotoxicity, calcification in calcinosis of mice, glycogen accumulation in the glycogenoses, lipofuscinosis in cattle, fatty degeneration in erucic acid cardiotoxicity, myofiber disarray in hypertrophic cardiomyopathy, and lymphocytic inflammation with inclusion bodies in canine parvoviral myocarditis. The myocardial diseases represent the largest group in the spectrum of spontaneous cardiac diseases of animals. Pericardial and endocardial diseases and congential cardiac diseases are

Cardiac microvascular rarefaction in hyperthyroidism-induced left ventricle dysfunction.

PubMed

Freitas, Felipe; Estato, Vanessa; Carvalho, Vinícius Frias; Torres, Rafael Carvalho; Lessa, Marcos Adriano; Tibiriçá, Eduardo

2013-10-01

The pathophysiology underlying hyperthyroidism-induced left ventricle (LV) dysfunction and hypertrophy directly involves the heart and indirectly involves the neuroendocrine systems. The effects of hyperthyroidism on the microcirculation are still controversial in experimental models. We investigated the effects of hyperthyroidism on the cardiac function and microcirculation of an experimental rat model. Male Wistar rats (170-250 g) were divided into two groups: the euthyroid group (n = 10), which was treated with 0.9% saline solution, and the hyperthyroid group (n = 10), which was treated with l-thyroxine (600 μg/kg/day, i.p.) during 14 days. An echocardiographic study was performed to evaluate the alterations in cardiac function, structure and geometry. The structural capillary density and the expression of angiotensin II AT1 receptor in the LV were analyzed using histochemistry and immunohistochemistry, respectively. Hyperthyroidism was found to induce profound cardiovascular alterations, such as systolic hypertension, tachycardia, LV dysfunction, cardiac hypertrophy, and myocardial fibrosis. This study demonstrates the existence of structural capillary rarefaction and the down-regulation of the cardiac angiotensin II AT1 receptor in the myocardium of hyperthyroid rats in comparison with euthyroid rats. Microvascular rarefaction may be involved in the pathophysiology of hyperthyroidism-induced cardiovascular alterations. © 2013 John Wiley & Sons Ltd.

Selective cerebro-myocardial perfusion in complex congenital aortic arch pathology: a novel technique.

PubMed

De Rita, Fabrizio; Lucchese, Gianluca; Barozzi, Luca; Menon, Tiziano; Faggian, Giuseppe; Mazzucco, Alessandro; Luciani, Giovanni Battista

2011-11-01

Simultaneous cerebro-myocardial perfusion has been described in neonatal and infant arch surgery, suggesting a reduction in cardiac morbidity. Here reported is a novel technique for selective cerebral perfusion combined with controlled and independent myocardial perfusion during surgery for complex or recurrent aortic arch lesions. From April 2008 to April 2011, 10 patients with arch pathology underwent surgery (two hypoplastic left heart syndrome [HLHS], four recurrent arch obstruction, two aortic arch hypoplasia + ventricular septal defect [VSD], one single ventricle + transposition of the great arteries + arch hypoplasia, one interrupted aortic arch type B + VSD). Median age was 63 days (6 days-36 years) and median weight 4.0 kg (1.6-52). Via midline sternotomy, an arterial cannula (6 or 8 Fr for infants) was directly inserted into the innominate artery or through a polytetrafluoroethylene (PTFE) graft (for neonates <2.0 kg). A cardioplegia delivery system was inserted into the aortic root. Under moderate hypothermia, ascending and descending aorta were cross-clamped, and "beating heart and brain" aortic arch repair was performed. Arch repair was composed of patch augmentation in five, end-to-side anastomosis in three, and replacement in two patients. Average cardiopulmonary bypass time was 163 ± 68 min (71-310). In two patients only (one HLHS, one complex single ventricle), a period of cardiac arrest was required to complete intracardiac repair. In such cases, antegrade blood cardioplegia was delivered directly via the same catheter used for selective myocardial perfusion. Average time of splanchnic ischemia during cerebro-myocardial perfusion was 39 ± 18 min (17-69). Weaning from cardiopulmonary bypass was achieved without inotropic support in three and with low dose in seven patients. One patient required veno-arterial extracorporeal membrane oxygenation. Four patients, body weight <3.0 kg, needed delayed sternal closure. No neurologic dysfunction was noted

Deficiency of Rac1 Blocks NADPH Oxidase Activation, Inhibits Endoplasmic Reticulum Stress, and Reduces Myocardial Remodeling in a Mouse Model of Type 1 Diabetes

PubMed Central

Li, Jianmin; Zhu, Huaqing; Shen, E; Wan, Li; Arnold, J. Malcolm O.; Peng, Tianqing

2010-01-01

OBJECTIVE Our recent study demonstrated that Rac1 and NADPH oxidase activation contributes to cardiomyocyte apoptosis in short-term diabetes. This study was undertaken to investigate if disruption of Rac1 and inhibition of NADPH oxidase would prevent myocardial remodeling in chronic diabetes. RESEARCH DESIGN AND METHODS Diabetes was induced by injection of streptozotocin in mice with cardiomyocyte-specific Rac1 knockout and their wild-type littermates. In a separate experiment, wild-type diabetic mice were treated with vehicle or apocynin in drinking water. Myocardial hypertrophy, fibrosis, endoplasmic reticulum (ER) stress, inflammatory response, and myocardial function were investigated after 2 months of diabetes. Isolated adult rat cardiomyocytes were cultured and stimulated with high glucose. RESULTS In diabetic hearts, NADPH oxidase activation, its subunits' expression, and reactive oxygen species production were inhibited by Rac1 knockout or apocynin treatment. Myocardial collagen deposition and cardiomyocyte cross-sectional areas were significantly increased in diabetic mice, which were accompanied by elevated expression of pro-fibrotic genes and hypertrophic genes. Deficiency of Rac1 or apocynin administration reduced myocardial fibrosis and hypertrophy, resulting in improved myocardial function. These effects were associated with a normalization of ER stress markers' expression and inflammatory response in diabetic hearts. In cultured cardiomyocytes, high glucose–induced ER stress was inhibited by blocking Rac1 or NADPH oxidase. CONCLUSIONS Rac1 via NADPH oxidase activation induces myocardial remodeling and dysfunction in diabetic mice. The role of Rac1 signaling may be associated with ER stress and inflammation. Thus, targeting inhibition of Rac1 and NADPH oxidase may be a therapeutic approach for diabetic cardiomyopathy. PMID:20522592

New Role for Interleukin-13 Receptor α1 in Myocardial Homeostasis and Heart Failure.

PubMed

Amit, Uri; Kain, David; Wagner, Allon; Sahu, Avinash; Nevo-Caspi, Yael; Gonen, Nir; Molotski, Natali; Konfino, Tal; Landa, Natalie; Naftali-Shani, Nili; Blum, Galia; Merquiol, Emmanuelle; Karo-Atar, Danielle; Kanfi, Yariv; Paret, Gidi; Munitz, Ariel; Cohen, Haim Y; Ruppin, Eytan; Hannenhalli, Sridhar; Leor, Jonathan

2017-05-20

The immune system plays a pivotal role in myocardial homeostasis and response to injury. Interleukins-4 and -13 are anti-inflammatory type-2 cytokines, signaling via the common interleukin-13 receptor α1 chain and the type-2 interleukin-4 receptor. The role of interleukin-13 receptor α1 in the heart is unknown. We analyzed myocardial samples from human donors (n=136) and patients with end-stage heart failure (n=177). We found that the interleukin-13 receptor α1 is present in the myocardium and, together with the complementary type-2 interleukin-4 receptor chain Il4ra , is significantly downregulated in the hearts of patients with heart failure. Next, we showed that Il13ra1 -deficient mice develop severe myocardial dysfunction and dyssynchrony compared to wild-type mice (left ventricular ejection fraction 29.7±9.9 versus 45.0±8.0; P =0.004, left ventricular end-diastolic diameter 4.2±0.2 versus 3.92±0.3; P =0.03). A bioinformatic analysis of mouse hearts indicated that interleukin-13 receptor α1 regulates critical pathways in the heart other than the immune system, such as extracellular matrix (normalized enrichment score=1.90; false discovery rate q=0.005) and glucose metabolism (normalized enrichment score=-2.36; false discovery rate q=0). Deficiency of Il13ra1 was associated with reduced collagen deposition under normal and pressure-overload conditions. The results of our studies in humans and mice indicate, for the first time, a role of interleukin-13 receptor α1 in myocardial homeostasis and heart failure and suggests a new therapeutic target to treat heart disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Magnetic Resonance Imaging (MRI) for the Assessment of Myocardial Viability

PubMed Central

2010-01-01

Imaging for the Assessment of Myocardial Viability: An Evidence-Based Analysis Objective The objective of this analysis is to assess the effectiveness and cost-effectiveness of cardiovascular magnetic resonance imaging (cardiac MRI) for the assessment of myocardial viability. To evaluate the effectiveness of cardiac MRI viability imaging, the following outcomes were examined: the diagnostic accuracy in predicting functional recovery and the impact of cardiac MRI viability imaging on prognosis (mortality and other patient outcomes). Clinical Need: Condition and Target Population Left Ventricular Systolic Dysfunction and Heart Failure Heart failure is a complex syndrome characterized by the heart’s inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) 1 is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. Treatment Options In general, there are three options for the treatment of heart failure: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts

Imaging and Modeling of Myocardial Metabolism

PubMed Central

Jamshidi, Neema; Karimi, Afshin; Birgersdotter-Green, Ulrika; Hoh, Carl

2010-01-01

Current imaging methods have focused on evaluation of myocardial anatomy and function. However, since myocardial metabolism and function are interrelated, metabolic myocardial imaging techniques, such as positron emission tomography, single photon emission tomography, and magnetic resonance spectroscopy present novel opportunities for probing myocardial pathology and developing new therapeutic approaches. Potential clinical applications of metabolic imaging include hypertensive and ischemic heart disease, heart failure, cardiac transplantation, as well as cardiomyopathies. Furthermore, response to therapeutic intervention can be monitored using metabolic imaging. Analysis of metabolic data in the past has been limited, focusing primarily on isolated metabolites. Models of myocardial metabolism, however, such as the oxygen transport and cellular energetics model and constraint-based metabolic network modeling, offer opportunities for evaluation interactions between greater numbers of metabolites in the heart. In this review, the roles of metabolic myocardial imaging and analysis of metabolic data using modeling methods for expanding our understanding of cardiac pathology are discussed. PMID:20559785

Aldehydic load and aldehyde dehydrogenase 2 profile during the progression of post-myocardial infarction cardiomyopathy: benefits of Alda-1

PubMed Central

Gomes, Katia M.S.; Bechara, Luiz R.G.; Lima, Vanessa M.; Ribeiro, Márcio A.C.; Campos, Juliane C.; Dourado, Paulo M.; Kowaltowski, Alicia J.; Mochly-Rosen, Daria; Ferreira, Julio C.B.

2015-01-01

Background/Objectives We previously demonstrated that reducing cardiac aldehydic load by aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme responsible for metabolizing the major lipid peroxidation product, protects against acute ischemia/reperfusion injury and chronic heart failure. However, time-dependent changes in ALDH2 profile, aldehydic load and mitochondrial bioenergetics during progression of post-myocardial infarction (post-MI) cardiomyopathy is unknown and should be established to determine the optimal time window for drug treatment. Methods Here we characterized cardiac ALDH2 activity and expression, lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE) adduct formation, glutathione pool and mitochondrial energy metabolism and H2O2 release during the 4 weeks after permanent left anterior descending (LAD) coronary artery occlusion in rats. Results We observed a sustained disruption of cardiac mitochondrial function during the progression of post-MI cardiomyopathy, characterized by >50% reduced mitochondrial respiratory control ratios and up to 2 fold increase in H2O2 release. Mitochondrial dysfunction was accompanied by accumulation of cardiac and circulating lipid peroxides and 4-HNE protein adducts and down-regulation of electron transport chain complexes I and V. Moreover, increased aldehydic load was associated with a 90% reduction in cardiac ALDH2 activity and increased glutathione pool. Further supporting an ALDH2 mechanism, sustained Alda-1 treatment (starting 24hrs after permanent LAD occlusion surgery) prevented aldehydic overload, mitochondrial dysfunction and improved ventricular function in post-MI cardiomyopathy rats. Conclusion Taken together, our findings demonstrate a disrupted mitochondrial metabolism along with an insufficient cardiac ALDH2-mediated aldehyde clearance during the progression of ventricular dysfunction, suggesting a potential therapeutic value of ALDH2 activators during the progression of post-myocardial infarction

Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies

PubMed Central

Korosoglou, G; Hansen, A; Bekeredjian, R; Filusch, A; Hardt, S; Wolf, D; Schellberg, D; Katus, H A; Kuecherer, H

2006-01-01

Objective To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. Methods and results Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2  =  0.92 versus r2  =  0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (κ  =  0.87 v κ  =  0.75, p < 0.05). Conclusion MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine. PMID:15939722

Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies.

PubMed

Korosoglou, G; Hansen, A; Bekeredjian, R; Filusch, A; Hardt, S; Wolf, D; Schellberg, D; Katus, H A; Kuecherer, H

2006-03-01

To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2 = 0.92 versus r2 = 0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (kappa = 0.87 v kappa = 0.75, p < 0.05). MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine.

[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

Extracellular Superoxide Dismutase Deficiency Exacerbates Pressure Overload–Induced Left Ventricular Hypertrophy and Dysfunction

PubMed Central

Lu, Zhongbing; Xu, Xin; Hu, Xinli; Zhu, Guangshuo; Zhang, Ping; van Deel, Elza D.; French, Joel P.; Fassett, John T.; Oury, Tim D.; Bache, Robert J.; Chen, Yingjie

2008-01-01

Extracellular superoxide dismutase (SOD) contributes only a small fraction to total SOD activity in the normal heart but is strategically located to scavenge free radicals in the extracellular compartment. To examine the physiological significance of extracellular SOD in the response of the heart to hemodynamic stress, we studied the effect of extracellular SOD deficiency on transverse aortic constriction (TAC)–induced left ventricular remodeling. Under unstressed conditions extracellular SOD deficiency had no effect on myocardial total SOD activity, the ratio of glutathione:glutathione disulfide, nitrotyrosine content, or superoxide anion production but resulted in small but significant increases in myocardial fibrosis and ventricular mass. In response to TAC for 6 weeks, extracellular SOD-deficient mice developed more severe left ventricular hypertrophy (heart weight increased 2.56-fold in extracellular SOD-deficient mice as compared with 1.99-fold in wild-type mice) and pulmonary congestion (lung weight increased 2.92-fold in extracellular SOD-deficient mice as compared with 1.84-fold in wild-type mice). Extracellular SOD-deficient mice also had more ventricular fibrosis, dilation, and a greater reduction of left ventricular fractional shortening and rate of pressure development after TAC. TAC resulted in greater increases of ventricular collagen I, collagen III, matrix metalloproteinase-2, matrix metalloproteinase-9, nitrotyrosine, and superoxide anion production. TAC also resulted in a greater decrease of the ratio of glutathione:glutathione disulfide in extracellular SOD-deficient mice. The finding that extracellular SOD deficiency had minimal impact on myocardial overall SOD activity but exacerbated TAC induced myocardial oxidative stress, hypertrophy, fibrosis, and dysfunction indicates that the distribution of extracellular SOD in the extracellular space is critically important in protecting the heart against pressure overload. PMID:17998475

Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials.

PubMed

Danchin, Nicolas; Cucherat, Michel; Thuillez, Christian; Durand, Eric; Kadri, Zena; Steg, Philippe G

2006-04-10

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced. Angiotensin-converting enzyme inhibitors reduce total mortality and major

Roselle is cardioprotective in diet-induced obesity rat model with myocardial infarction.

PubMed

Si, Lislivia Yiang-Nee; Ali, Siti Aishah Mohd; Latip, Jalifah; Fauzi, Norsyahida Mohd; Budin, Siti Balkis; Zainalabidin, Satirah

2017-12-15

Obesity increase the risks of hypertension and myocardial infarction (MI) mediated by oxidative stress. This study was undertaken to investigate the actions of roselle aqueous extract (R) on cardiotoxicity in obese (OB) rats and thereon OB rats subjected to MI. Male Sprague-Dawley rats were fed with either normal diet or high-fat diet for 8weeks. Firstly, OB rats were divided into (1) OB and (2) OB+R (100mg/kg, p.o, 28days). Then, OB rats were subjected to MI (ISO, 85mg/kg, s.c, 2days) and divided into three groups: (1) OB+MI, (2) OB+MI+R and (3) OB+MI+enalapril for another 4weeks. Roselle ameliorated OB and OB+MI's cardiac systolic dysfunction and reduced cardiac hypertrophy and fibrosis. The increased oxidative markers and decreased antioxidant enzymes in OB and OB+MI groups were all attenuated by roselle. These observations indicate the protective effect of roselle on cardiac dysfunction in OB and OB+MI rats, which suggest its potential to be developed as a nutraceutical product for obese and obese patients with MI in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

TGF-β improves myocardial function and prevents apoptosis induced by anoxia-reoxygenation, through the reduction of endoplasmic reticulum stress.

PubMed

Wang, Yufeng; Zong, Ligeng; Wang, Xiaolei

2016-01-01

Transforming growth factor-β (TGF-β) is known for its role in ventricular remodeling, inflammatory response, cell survival, and apoptosis. However, its role in improving myocardial function in rat hearts subjected to ischemia-reperfusion (I/R) and protecting against apoptosis induced in cardiomyocytes by anoxia-reoxygenation (A/R) has not been elucidated. This study investigated the protective effects and molecular mechanisms of TGF-β on myocardial function and cardiomyocyte apoptosis. We used TUNEL staining, we tested cell viability, and we measured mitochondrial membrane potential and levels of mitochondrial ROS after 6 h of simulated anoxia together with various durations of simulated reoxygenation in H9c2 cells. We further observed the contractile function in rat hearts after they were subjected to 30 min global ischemia and 180 min reperfusion. Pretreatment with TGF-β markedly inhibited apoptosis in H9c2 cells, as evidenced by increased cell viability and decreased numbers of TUNEL-positive cells, maintained mitochondrial membrane potential, and diminished mitochondrial production of reactive oxygen species (ROS). These changes were associated with the inhibition of endoplasmic reticulum (ER) stress-dependent markers of apoptosis (GRP78, CHOP, caspase-12, and JNK), and the modulation of the expression of Bcl2/Bax. Furthermore, TGF-β improved I/R-induced myocardial contractile dysfunction. All of these protective effects were concentration-dependent. Our results show that TGF-β prevents A/R-induced apoptosis of cardiomyocytes and improves myocardial function in rat hearts injured by I/R.

MicroRNA-214 protects against hypoxia/reoxygenation induced cell damage and myocardial ischemia/reperfusion injury via suppression of PTEN and Bim1 expression.

PubMed

Wang, Xiaohui; Ha, Tuanzhu; Hu, Yuanping; Lu, Chen; Liu, Li; Zhang, Xia; Kao, Race; Kalbfleisch, John; Williams, David; Li, Chuanfu

2016-12-27

Myocardial apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Activation of PI3K/Akt signaling protects the myocardium from I/R injury. This study investigated the role of miR-214 in hypoxia/reoxygenation (H/R)-induced cell damage in vitro and myocardial I/R injury in vivo. H9C2 cardiomyoblasts were transfected with lentivirus expressing miR-214 (LmiR-214) or lentivirus expressing scrambled miR-control (LmiR-control) respectively, to establish cell lines of LmiR-214 and LmiR-control. The cells were subjected to hypoxia for 4 h followed by reoxygenation for 24 h. Transfection of LmiR-214 suppresses PTEN expression, significantly increases the levels of Akt phosphorylation, markedly attenuates LDH release, and enhances the viability of the cells subjected to H/R. In vivo transfection of mouse hearts with LmiR-214 significantly attenuates I/R induced cardiac dysfunction and reduces I/R-induced myocardial infarct size. LmiR-214 transfection significantly attenuates I/R-induced myocardial apoptosis and caspase-3/7 and caspase-8 activity. Increased expression of miR-214 by transfection of LmiR-214 suppresses PTEN expression, increases the levels of phosphorylated Akt, represses Bim1 expression and induces Bad phosphorylation in the myocardium. In addition, in vitro data shows transfection of miR-214 mimics to H9C2 cells suppresses the expression and translocation of Bim1 from cytosol to mitochondria and induces Bad phosphorylation. Our in vitro and in vivo data suggests that miR-214 protects cells from H/R induced damage and attenuates I/R induced myocardial injury. The mechanisms involve activation of PI3K/Akt signaling by targeting PTEN expression, induction of Bad phosphorylation, and suppression of Bim1 expression, resulting in decreases in I/R-induced myocardial apoptosis.

MYOCARDIAL AKT: THE OMNIPRESENT NEXUS

PubMed Central

Sussman, Mark A.; Völkers, Mirko; Fischer, Kimberlee; Bailey, Brandi; Cottage, Christopher T.; Din, Shabana; Gude, Natalie; Avitabile, Daniele; Alvarez, Roberto; Sundararaman, Balaji; Quijada, Pearl; Mason, Matt; Konstandin, Mathias H.; Malhowski, Amy; Cheng, Zhaokang; Khan, Mohsin; McGregor, Michael

2013-01-01

One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses. PMID:21742795

Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10

PubMed Central

Nogueira, Luciana Gabriel; Santos, Ronaldo Honorato Barros; Ianni, Barbara Maria; Fiorelli, Alfredo Inácio; Mairena, Eliane Conti; Benvenuti, Luiz Alberto; Frade, Amanda; Donadi, Eduardo; Dias, Fabrício; Saba, Bruno; Wang, Hui-Tzu Lin; Fragata, Abilio; Sampaio, Marcelo; Hirata, Mario Hiroyuki; Buck, Paula; Mady, Charles; Bocchi, Edimar Alcides; Stolf, Noedir Antonio; Kalil, Jorge; Cunha-Neto, Edecio

2012-01-01

Background Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2–6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that

Rescue of neonatal cardiac dysfunction in mice by administration of cardiac progenitor cells in utero

PubMed Central

Liu, Xiaoli; Hall, Sean R. R.; Wang, Zhihong; Huang, He; Ghanta, Sailaja; Di Sante, Moises; Leri, Annarosa; Anversa, Piero; Perrella, Mark A.

2015-01-01

Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family. We previously showed that disruption of the Speg gene locus in mice leads to a dilated cardiomyopathy with immature-appearing cardiomyocytes. Here we show that cardiomyopathy of Speg−/− mice arises as a consequence of defects in cardiac progenitor cell (CPC) function, and that neonatal cardiac dysfunction can be rescued by in utero injections of wild-type CPCs into Speg−/− foetal hearts. CPCs harvested from Speg−/− mice display defects in clone formation, growth and differentiation into cardiomyocytes in vitro, which are associated with cardiac dysfunction in vivo. In utero administration of wild-type CPCs into the hearts of Speg−/− mice results in CPC engraftment, differentiation and myocardial maturation, which rescues Speg−/− mice from neonatal heart failure and increases the number of live births by fivefold. We propose that in utero administration of CPCs may have future implications for treatment of neonatal heart diseases. PMID:26593099

Myocardial tissue deformation is reduced in subjects with coronary microvascular dysfunction but not rescued by treatment with Ranolazine

PubMed Central

Nelson, Michael D.; Sharif, Behzad; Shaw, Jaime L.; Cook-Wiens, Galen; Wei, Janet; Shufelt, Chrisandra; Mehta, Puja K.; Thomson, Louise EJ; Berman, Daniel S.; Thompson, Richard B.; Handberg, Eileen M.; Pepine, Carl J.; Li, Debiao; Bairey Merz, C. Noel

2016-01-01

Background Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine—a late-sodium current inhibitor—improves diastolic function in animal models, and subjects with obstructive CAD. We hypothesized that ranolazine would beneficially alter diastolic function in CMD. Methods To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images: a) acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD, and b) from 43 healthy reference controls. Results Diastolic strain rate was impaired in CMD vs. controls (circumferential diastolic strain rate: 99.9 ± 2.5%/s vs. 120.1 ± 4.0%/s, p=0.0003; radial diastolic strain rate: −199.5 ± 5.5%/s vs. −243.1 ± 9.6%/s, p=0.0008, case vs. control). Moreover, peak systolic circumferential (CS) and radial (RS) strain were also impaired in cases vs. controls (CS: −18.8 ± 0.3% vs. −20.7 ± 0.3%; RS: 35.8 ± 0.7% vs. 41.4 ± 0.9%; respectively; both p < 0.0001), despite similar and preserved ejection fraction. In contrast to our hypothesis however, we observed no significant changes in left ventricular diastolic function in CMD cases after two weeks of ranolazine vs. placebo. Conclusions The case-control comparison both confirms and extends our prior observations of diastolic dysfunction in CMD. That CMD cases were also found to have sub-clinical systolic dysfunction is a novel finding, highlighting the utility of this retrospective approach. In contrast to previous studies in obstructive CAD, ranolazine did not improve diastolic function in CMD. PMID:28004395

[Clinical significance of myocardial 123I-BMIPP imaging in patients with myocardial infarction].

PubMed

Narita, M; Kurihara, T; Shindoh, T; Honda, M

1997-03-01

In order to clarify the characteristics of fatty acid metabolism in patients with myocardial infarction (MI), we performed myocardial imaging with 123I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) and we compared these findings with exercise stress (Ex) and resting myocardial perfusion imaging with 99mTc-methoxyisobutylisonitrile (MIBI) and left ventricular wall motion index (WMI) which were obtained by left ventriculography. We studied 55 patients with MI, 14 patients with recent MI (RMI) and 41 patients with old MI (OMI), and myocardial images were divided into 17 segments and myocardial uptake of the radionuclide was graded from 0 (normal) to 3 (maximal abnormality). In 28 patients we compared segmental defect score (SDS) with WMI which were obtained by centerline method at the corresponded segments. As a whole, the mean total defect scores (TDSs) of BMIPP and Ex were similar and they were greater than the mean TDS of resting perfusion. In 30 patient (55%) TDS of BMIPP was greater than that of TDS of resting perfusion. In 24 patients perfusion abnormality developed by Ex and the location of BMIPP abnormality coincided with the abnormality of Ex. But in the other 6 patients Ex did not induce any abnormality and they were all RMI and infarcted coronary artery was patent. However in the group with TDS of BMIPP identical to TDS of resting perfusion (25 patients), 92% did not show myocardial perfusion abnormality after Ex. In the comparison of SDS and WMI, myocardial segments were divided into 3 groups; both SDSs of BMIPP and resting perfusion were normal or borderline abnormality (Group 1, 82 segments), SDS of resting perfusion was normal or borderline and SDS of BMIPP was definitely abnormal (Group 2, 10 segments) and both SDSs of BMIPP and resting perfusion were definitely abnormal (Group 3, 48 segments). In Group 1, WMS (-0.41 +/- 0.77) was significantly (p < 0.001) greater than those of Group 2 (-2.14 +/- 0.50) and Group 3 (-2.32 +/- 0.67). But there was

Effects of aluminum oxide (Al2O3) nanoparticles on ECG, myocardial inflammatory cytokines, redox state, and connexin 43 and lipid profile in rats: possible cardioprotective effect of gallic acid.

PubMed

El-Hussainy, El-Hussainy M A; Hussein, Abdelaziz M; Abdel-Aziz, Azza; El-Mehasseb, Ibrahim

2016-08-01

The objectives of present study were to examine the effects of aluminum oxide (Al2O3) nanoparticles on myocardial functions, electrical activities, morphology, inflammation, redox state, and myocardial expression of connexin 43 (Cx43) and the effect of gallic acid (GA) on these effects in a rat animal model. Forty male albino rats were divided into 4 equal groups: the control (normal) group; the Al2O3 group, rats received Al2O3 (30 mg·kg(-1), i.p.) daily for 14 days; the nano-alumina group, rats received nano-alumina (30 mg·kg(-1), i.p.) daily for 14 days; and the nano-alumina + GA group, rats received GA (100 mg·kg(-1) orally once daily) for 14 days before nano-alumina administration. The results showed disturbed ECG variables and significant increases in serum levels of LDH, creatine phosphokinase (CPK), CK-MB, triglycerides (TGs), cholesterol and LDL, nitric oxide (NO), and TNF-α and myocardial concentrations of NO, TNF-α, and malondialdehyde (MDA), with significant decreases in serum HDL and myocardial GSH, SOD, catalase (CAT), and Cx43 expression in the nano-alumina group. Pretreatment with GA improved significantly all parameters except serum and myocardial NO. We concluded that chronic administration of Al2O3 NPs caused myocardial dysfunctions, and pretreatment with GA ameliorates myocardial injury induced by nano-alumina, probably through its hypolipidaemic, anti-inflammatory, and antioxidant effects and upregulation of Cx43 in heart.

Cardiac-specific overexpression of metallothionein attenuates myocardial remodeling and contractile dysfunction in l-NAME-induced experimental hypertension: Role of autophagy regulation.

PubMed

Yang, Lifang; Gao, Jian-Yuan; Ma, Jipeng; Xu, Xihui; Wang, Qiurong; Xiong, Lize; Yang, Jian; Ren, Jun

2015-09-02

Hypertension is an independent risk factor for heart disease and is responsible for the increased cardiac morbidity and mortality. Oxidative stress plays a key role in hypertensive heart diseases although the precise mechanism remains unclear. This study was designed to examine the effect of cardiac-specific overexpression of metallothionein, a cysteine-rich antioxidant, on myocardial contractile and intracellular Ca(2+) anomalies in N(G)-nitro-l-arginine methyl ester (l-NAME)-induced experimental hypertension and the mechanism involved with a focus on autophagy. Our results revealed that l-NAME treatment (14 days) led to hypertension and myocardial anomalies evidenced by interstitial fibrosis, cardiomyocyte hypertrophy, increased LV end systolic and diastolic diameters (LVESD and LVEDD) along with suppressed fractional shortening. l-NAME compromised cardiomyocyte contractile and intracellular Ca(2+) properties manifested as depressed peak shortening, maximal velocity of shortening/relengthening, electrically-stimulated rise in intracellular Ca(2+), elevated baseline and peak intracellular Ca(2+). These l-NAME-induced histological and mechanical changes were attenuated or reconciled by metallothionein. Protein levels of autophagy markers LC3B and p62 were decreased and increased, respectively. Autophagy signaling molecules AMPK, TSC2 and ULK1 were inactivated while those of mTOR and p70s6K were activated by l-NAME, the effects of which were ablated by metallothionein. Autophagy induction mimicked whereas autophagy inhibition nullified the beneficial effect of metallothionein against l-NAME. These findings suggested that metallothionein protects against l-NAME-induced myocardial anomalies possibly through restoration of autophagy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The prognostic value of biomarkers after a premature myocardial infarction.

PubMed

Pineda, Javier; Marín, Francisco; Marco, Pascual; Roldán, Vanessa; Valencia, José; Ruiz-Nodar, Juan Miguel; Romero, Diana Hernández; Sogorb, Francisco; Lip, Gregory Y H

2010-09-03

Intravascular thrombogenesis is influenced by a complex interplay of factors related to a procoagulant state, fibrinolysis, endothelial damage/dysfunction and inflammation. We hypothesised that abnormalities of these biological systems would contribute to outcome of coronary artery disease presenting at a young age. We performed a prospective study of 142 subjects presenting with acute myocardial infarction (AMI) at a young age (defined as age ≤45 years), to determine the clinical and laboratory predictors of cardiovascular events during 36 months of follow-up. We assessed conventional risk factors and abnormalities of thrombophilia [total homocysteine (tHcy), lipoprotein (a) [Lp(a)], antiphospholipid antibodies (APA)], as well as lipid profile (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides), fibrinogen and fibrin D-dimer (as indices of a hypercoagulable state and thrombogenesis), von Willebrand factor (vWF, an index of endothelial damage/dysfunction), tissue plasminogen activator [t-PA antigen] and its inhibitor [PAI-1 antigen] (as indices of fibrinolysis), and C-reactive protein [CRP] (an index of inflammation). In a multivariate analysis, the variables independently associated with cardiovascular events at follow-up were levels of homocysteine (OR 3.73, 95% CI (1.54-9.02); p=0.003), left ventricle systolic dysfunction (OR 3.04, 95% CI (1.00-9.25); p=0.050), and smoking habit (OR 2.79, 95% CI (1.09-7.14) p=0.032). Prognostic markers associated with cardiovascular events in premature CAD (young AMI subjects) were cigarette smoking and EF<50% of left ventricle as conventional clinical risk factors, as well as higher levels of homocysteine. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Is HIV a model of accelerated or accentuated aging?

PubMed

Pathai, Sophia; Bajillan, Hendren; Landay, Alan L; High, Kevin P

2014-07-01

Antiretroviral therapy has reduced the incidence of adverse events and early mortality in HIV-infected persons. Despite these benefits, important comorbidities that increase with age (eg, diabetes, cardiovascular disease, cancer, liver disease, and neurocognitive impairment) are more prevalent in HIV-infected persons than in HIV-uninfected persons at every age, and geriatric syndromes such as falls and frailty occur earlier in HIV-infected persons. This raises a critical research question: Does HIV accelerate aging through pathways and mechanisms common to the aging process or is HIV simply an additional risk factor for a wide number of chronic conditions, thus accentuating aging? Extensive literature review. The purpose of this review is to briefly outline the evidence that age-related clinical syndromes are exacerbated by HIV, examine the ways in which HIV is similar, and dissimilar from natural aging, and assess the validity of HIV as a model of premature aging. Specific biomarkers of aging are limited in HIV-infected hosts and impacted by antiretroviral therapy, and a high rate of modifiable life style confounders (eg, smoking, substance abuse, alcohol) and coinfections (eg, hepatitis) in HIV-infected participants. There is a need for validated biomarkers of aging in the context of HIV. Despite these differences, welldesigned studies of HIV-infected participants are likely to provide new opportunities to better understand the mechanisms that lead to aging and age-related diseases. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

VO(2peak), myocardial hypertrophy, and myocardial blood flow in endurance-trained men.

PubMed

Laaksonen, Marko S; Heinonen, Ilkka; Luotolahti, Matti; Knuuti, Juhani; Kalliokoski, Kari K

2014-08-01

Endurance training induces cardiovascular and metabolic adaptations, leading to enhanced endurance capacity and exercise performance. Previous human studies have shown contradictory results in functional myocardial vascular adaptations to exercise training, and we hypothesized that this may be related to different degrees of hypertrophy in the trained heart. We studied the interrelationships between peak aerobic power (V˙O2peak), myocardial blood flow (MBF) at rest and during adenosine-induced vasodilation, and parameters of myocardial hypertrophy in endurance-trained (ET, n = 31) and untrained (n = 17) subjects. MBF and myocardial hypertrophy were studied using positron emission tomography and echocardiography, respectively. Both V˙O2peak (P < 0.001) and left ventricular (LV) mass index (P < 0.001) were higher in the ET group. Basal MBF was similar between the groups. MBF during adenosine was significantly lower in the ET group (2.88 ± 1.01 vs 3.64 ± 1.11 mL·g·min, P < 0.05) but not when the difference in LV mass was taken into account. V˙O2peak correlated negatively with adenosine-stimulated MBF, but when LV mass was taken into account as a partial correlate, this correlation disappeared. The present results show that increased LV mass in ET subjects explains the reduced hyperemic myocardial perfusion in this subject population and suggests that excessive LV hypertrophy has negative effect on cardiac blood flow capacity.

Time course of hydrogen peroxide-thioredoxin balance and its influence on the intracellular signalling in myocardial infarction.

PubMed

Schenkel, Paulo Cavalheiro; Tavares, Angela Maria Vicente; Fernandes, Rafael Oliveira; Diniz, Gabriela Placoná; Ludke, Ana Raquel Lehenbauer; Ribeiro, Maria Flavia Marques; Araujo, Alex Sander da Rosa; Barreto-Chaves, Maria Luiza; Belló-Klein, Adriane

2012-06-01

We investigated the myocardial thioredoxin-1 and hydrogen peroxide concentrations and their association with some prosurvival and pro-apoptotic proteins, during the transition from myocardial infarction (MI) to heart failure in rats. Male Wistar rats were divided into the following six groups: three sham-operated groups and three MI groups, each at at 2, 7 and 28 days postsurgery. Cardiac function was analysed by echocardiography; the concentration of H(2)O(2) and the ratio of reduced to oxidized glutathione were measured spectrophotometrically, while the myocardial immunocontent of thioredoxin-1, angiotensin II, angiotensin II type 1 and type 2 receptors, p-JNK/JNK, p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK3β/GSK3β was evaluated by Western blot. Our results show that thioredoxin-1 appears to make an important contribution to the reduced H(2)O(2) concentration. It was associated with lower JNK expression in the early period post-MI (2 days). However, thioredoxin-1 decreased, while renin-angiotensin system markers and levels of H(2)O(2) increased, over 28 days post-MI, in parallel with some signalling proteins involved in maladaptative cardiac remodelling and ventricular dysfunction. These findings provide insight into the time course profile of endogenous antioxidant adaptation to ischaemic injury, which may be useful for the design of therapeutical strategies targeting oxidative stress post-MI.

Myocardial impairment detected by late gadolinium enhancement in hypertrophic cardiomyopathy: comparison with 99mTc-MIBI/tetrofosmin and 123I-BMIPP SPECT.

PubMed

Hashimura, Hiromi; Kiso, Keisuke; Yamada, Naoaki; Kono, Atsushi; Morita, Yoshiaki; Fukushima, Kazuto; Higashi, Masahiro; Noguchi, Teruo; Ishibashi-Ueda, Hatsue; Naito, Hiroaki; Sugimura, Kazuro

2013-06-17

Myocardial fibrosis is considered to be an important factor in myocardial dysfunction and sudden cardiac death in hypertrophic cardiomyopathy (HCM). The purpose of this study was to compare myocardial fibrosis detected by late gadolinium enhancement (LGE) on cardiac MRI with myocardial perfusion and fatty acid metabolism assessed by single photon emission computed tomography in HCM. We retrospectively evaluated 20 consecutive HCM patients (female, 7; mean age, 53.4 years) who underwent LGE, technetium-99m methoxyisobutylisonitrile/tetrofosmin (99mTc-MIBI/tetrofosmin), and iodine-123 beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging. We calculated the myocardium-to-lumen signal ratio (M/L) for LGE in 17 segments based on the American Heart Association statement. Scoring of 99mTc-MIBI/tetrofosmin (PI) and 123I-BMIPP (BM) was performed for each segment using a 5-point scale (0, normal; 4, highly decreased). Nineteen of 20 patients (95%) and 153 of 340 segments (45%) showed LGE. M/Ls were 0.42±0.16, 0.55±0.17, and 0.65±0.24 in PI0/BM0, PI0/BM1-4 and PI1-4/BM1-4, respectively. All M/Ls were significantly higher than that of a normal control (0.34±0.14) (p<0.001). Myocardial fibrosis in HCM can occur despite normal perfusion and fatty acid metabolism, and is more strongly associated with disorders of fatty acid metabolism than with perfusion abnormalities. M/L may be a useful indicator of disease severity.

Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation.

PubMed

Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

2016-01-01

The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease.

Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of /sup 99m/Tc pyrophosphate and gallium

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

Forman, M.B.; Sandler, M.P.; Sacks, G.A.

1983-03-01

A patient had severe congestive cardiomyopathy secondary to myocardial sarcoidosis. The clinical diagnosis was confirmed by radionuclide ventriculography, /sup 201/Tl, /sup 67/Ga, and /sup 99m/Tc pyrophosphate (TcPYP) scintigraphy. Myocardial TcPYP uptake has not been reported previously in sarcoidosis. In this patient, TcPYP was as useful as gallium scanning and thallium imaging in documenting the myocardial process.

Accentuated Osteoclastic Response to Parathyroid Hormone Undermines Bone Mass Acquisition in Osteonectin-null Mice

PubMed Central

do Reis, Luciene Machado; Kessler, Catherine B.; Adams, Douglas J.; Lorenzo, Joseph; Jorgetti, Vanda; Delany, Anne M.

2008-01-01

Matricellular proteins play a unique role in the skeleton as regulators of bone remodeling, and the matricellular protein osteonectin (SPARC, BM-40) is the most abundant non-collagenous protein in bone. In the absence of osteonectin, mice develop progressive low turnover osteopenia, particularly affecting trabecular bone. Polymorphisms in a regulatory region of the osteonectin gene are associated with bone mass in a subset of idiopathic osteoporosis patients, and these polymorphisms likely regulate osteonectin expression. Thus it is important to determine how osteonectin gene dosage affects skeletal function. Moreover, intermittent administration of parathyroid hormone (PTH) (1-34) is the only anabolic therapy approved for the treatment of osteoporosis, and it is critical to understand how modulators of bone remodeling, such as osteonectin, affect skeletal response to anabolic agents. In this study, 10 week old female wild type, osteonectin-haploinsufficient, and osteonectin-null mice (C57Bl/6 genetic background) were given 80 μg/kg body weight/day PTH(1-34) for 4 weeks. Osteonectin gene dosage had a profound effect on bone microarchitecture. The connectivity density of trabecular bone in osteonectin-haploinsufficient mice was substantially decreased compared with that of wild type mice, suggesting compromised mechanical properties. Whereas mice of each genotype had a similar osteoblastic response to PTH treatment, the osteoclastic response was accentuated in osteonectin-haploinsufficient and osteonectin-null mice. Eroded surface and osteoclast number were significantly higher in PTH-treated osteonectin-null mice, as was endosteal area. In vitro studies confirmed that PTH induced the formation of more osteoclast-like cells in marrow from osteonectin-null mice compared with wild type. PTH treated osteonectin-null bone marrow cells expressed more RANKL mRNA compared with wild type. However, the ratio of RANKL:OPG mRNA was somewhat lower in PTH treated osteonectin

Early detection of right ventricular dysfunction using transthoracic echocardiography in ARDS: a more objective approach.

PubMed

Wadia, Subeer Kanwar; Shah, Trushil G; Hedstrom, Grady; Kovach, Julie A; Tandon, Rajive

2016-12-01

Right ventricular (RV) dysfunction is an independent predictor of morbidity and mortality in acute respiratory distress syndrome (ARDS). Our goal was to describe morphologic changes in the RV using objective measures on transthoracic echocardiography (TTE) that occur following ARDS. We retrospectively measured changes in the following RV parameters from a pre-ARDS TTE to an ARDS TTE: tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI), fractional area change (FAC), systolic pulmonary artery pressure (SPAP), peak tricuspid regurgitant (TR) velocity, and septal shift. Over 24 months, 14 patients met inclusion/exclusion criteria. Mean TAPSE decreased from 22.4 mm pre-ARDS to 16.3 mm during ARDS, P<.001. Mean MPI increased from 0.19 to 0.38, P=.001. Mean FAC decreased from 60.8% to 41.2%, P=.003. Peak TR velocity increased from 2.67 m/s pre-ARDS to 3.31 m/s during ARDS, P=.02. SPAP and septal shift demonstrated trends but not statistically different between pre-ARDS and ARDS states. TAPSE correlated with ARDS severity (PaO 2 /FiO 2 ratios), P=.004, and was lower among 30-day nonsurvivors compared with survivors, P=.002. Mild RV dysfunction is common after ARDS onset. RV morphologic changes coupled with dysfunction can be detected noninvasively through TTE changes with TAPSE, MPI, and FAC. Mild RV dysfunction by TAPSE is associated with ARDS severity and mortality. © 2016, Wiley Periodicals, Inc.

Mitochondrial dysfunction in myocardium obtained from clinically normal dogs, clinically normal anesthetized dogs, and dogs with dilated cardiomyopathy.

PubMed

Sleeper, Meg M; Rosato, Bradley P; Bansal, Seema; Avadhani, Narayan G

2012-11-01

To compare mitochondrial complex I and complex IV activity in myocardial mitochondria of clinically normal dogs, clinically normal dogs exposed to inhalation anesthesia, and dogs affected with dilated cardiomyopathy. Myocardial samples obtained from 21 euthanized dogs (6 clinically normal [control] dogs, 5 clinically normal dogs subjected to inhalation anesthesia with isoflurane prior to euthanasia, 5 dogs with juvenile-onset dilated cardiomyopathy, and 5 dogs with adult-onset dilated cardiomyopathy). Activity of mitochondrial complex I and complex IV was assayed spectrophotometrically in isolated mitochondria from left ventricular tissue obtained from the 4 groups of dogs. Activity of complex I and complex IV was significantly decreased in anesthetized dogs, compared with activities in the control dogs and dogs with juvenile-onset or adult-onset dilated cardiomyopathy. Inhalation anesthesia disrupted the electron transport chain in the dogs, which potentially led to an outburst of reactive oxygen species that caused mitochondrial dysfunction. Inhalation anesthesia depressed mitochondrial function in dogs, similar to results reported in other species. This effect is important to consider when anesthetizing animals with myocardial disease and suggested that antioxidant treatments may be beneficial in some animals. Additionally, this effect should be considered when designing studies in which mitochondrial enzyme activity will be measured. Additional studies that include a larger number of animals are warranted.

Magnetic resonance imaging (MRI) for the assessment of myocardial viability: an evidence-based analysis.

PubMed

2010-01-01

ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based Analysis The objective of this analysis is to assess the effectiveness and cost-effectiveness of cardiovascular magnetic resonance imaging (cardiac MRI) for the assessment of myocardial viability. To evaluate the effectiveness of cardiac MRI viability imaging, the following outcomes were examined: the diagnostic accuracy in predicting functional recovery and the impact of cardiac MRI viability imaging on prognosis (mortality and other patient outcomes). CONDITION AND TARGET POPULATION LEFT VENTRICULAR SYSTOLIC DYSFUNCTION AND HEART FAILURE: Heart failure is a complex syndrome characterized by the heart's inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) () is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. IN GENERAL, THERE ARE THREE OPTIONS FOR THE TREATMENT OF HEART FAILURE: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option

Ultrasound imaging of propagation of myocardial contraction for non-invasive identification of myocardial ischemia

NASA Astrophysics Data System (ADS)

Matsuno, Yuya; Taki, Hirofumi; Yamamoto, Hiroaki; Hirano, Michinori; Morosawa, Susumu; Shimokawa, Hiroaki; Kanai, Hiroshi

2017-07-01

Non-invasive identification of ischemic regions is important for diagnosis and treatment of myocardial infarction. In the present study, ultrasound measurement was applied to the interventricular septum of three open-chest swine hearts. The properties of the myocardial contraction response of the septum were compared between normal and acute ischemic conditions, where the acute ischemic condition of the septum originated from direct avascularization of the left anterior descending (LAD) coronary artery. The result showed that the contraction response propagated from the basal side to the apical side along the septum. The estimated propagation velocities in the normal and acute ischemic conditions were 3.6 and 1.9 m/s, respectively. This finding indicates that acute ischemia which occurred 5 s after the avascularization of the LAD promptly suppressed the propagation velocity through the ventricular septum to about half the normal velocity. It was suggested that the myocardial ischemic region could be identified using the difference in the propagation velocity of the myocardial response to contraction.

Impact of hyperventilation and apnea on myocardial oxygenation in patients with obstructive sleep apnea - An oxygenation-sensitive CMR study.

PubMed

Roubille, François; Fischer, Kady; Guensch, Dominik P; Tardif, Jean-Claude; Friedrich, Matthias G

2017-02-01

Oxygenation-sensitive cardiovascular magnetic resonance imaging (OS-CMR) is an emerging technique that can monitor changes in myocardial oxygenation in vivo. Obstructive sleep apnea syndrome (OSAS) is associated with endothelial and microcirculatory dysfunction and increased cardiovascular morbidity and mortality. Little is known about myocardial responses to apnea in patients with OSAS. We hypothesized that the coronary vascular response to hyperventilation and long breath-hold is diminished in patients with OSAS when compared to healthy volunteers. Twenty-nine OSAS patients and 36 healthy volunteers were prospectively enrolled. All CMR scans were performed on a clinical 3T system. Participants performed a breathing maneuver with 60s of hyperventilation followed by a maximal breath-hold. During the breath-hold, OS-CMR images were continuously acquired and signal intensity changes were measured by a blinded reader. Patients with OSAS were older than healthy volunteers (p<0.01) and presented more co-morbidities; 66% were currently treated with nocturnal positive airway pressure. Compared to healthy participants, the expected increase of myocardial oxygenation during the first 15s of the breath-hold was significantly lower in patients with OSAS (2.6±8.3% vs. 6.7±5.6%; p<0.05), and remained reduced at all time points during the breath-hold. Importantly this result was mainly driven by patients under continuous positive airway pressure (CPAP), suggesting that CPAP might have a greater impact on increase of myocardial oxygenation rather than OSAS itself. The myocardial vascular response to combined breathing maneuvers of hyperventilation followed by voluntary apnea is blunted in patients with obstructive sleep apnea. Clinical studies should now further define the clinical role of oxygenation-sensitive CMR in patients with respiratory disorders. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Predictive value of myocardial perfusion single-photon emission computed tomography and the impact of renal function on cardiac death.

PubMed

Hakeem, Abdul; Bhatti, Sabha; Dillie, Kathryn Sullivan; Cook, Jeffrey R; Samad, Zainab; Roth-Cline, Michelle D; Chang, Su Min

2008-12-09

Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated. We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15+/-0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score>or=4). Ischemia was defined as a summed stress score >or=4 plus a summed difference score >or=2, and scar was defined as a summed difference score <2 plus a summed stress score >or=4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL . min(-1) . 1.73 m(-2)) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global chi(2) 207.5 versus 169.3, P<0.0001). MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac

Left ventricular function quantified by myocardial strain imaging in small-breed dogs with chronic mitral regurgitation.

PubMed

Smith, Danielle N; Bonagura, John D; Culwell, Nicole M; Schober, Karsten E

2012-03-01

The presence of left ventricular (LV) systolic dysfunction may influence prognosis or therapy in dogs with chronic mitral regurgitation (MR). Assessment of LV function in MR by conventional echocardiography is confounded by altered ventricular loading. Myocardial deformation (strain) imaging might offer more sensitive estimates of LV function in this disease. Prospectively measure myocardial strain in dogs with asymptomatic MR compared to a control group. Forty healthy dogs (3.5-11.5 kg): 20 Controls; 20 dogs with MR and LV remodeling (Stage B2), were evaluated in this study. LV size and function were assessed in a short-axis plane. Segmental radial strain and strain rate and global circumferential strain were measured using a 2D echocardiographic speckle-tracking algorithm (GE EchoPAC). Groups were compared using Bonferroni t-tests. Influences of heart rate and body weight were explored with linear regression. The MR group had significantly greater mean values for heart rate, LV size, and LV systolic function. Specifically, LV diastolic diameter, diastole area, shortening fraction, averaged peak systolic and early diastolic radial strain, global circumferential strain, and averaged radial strain rate were significantly greater in the MR group (p < 0.015 to p < 0.001). Strain was unrelated to weight, but weakly correlated with heart rate. Similar to conventional indices, Stage B2 dogs with MR demonstrate hyperdynamic deformation in the short-axis plane. Short-axis strain variables measured by 2D speckle tracking are greater than for controls of similar age and weight. These results imply either preserved LV systolic function or that LV dysfunction is masked by altered ventricular loading. Copyright © 2012 Elsevier B.V. All rights reserved.

Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation

PubMed Central

Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

2016-01-01

Purpose: The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. Methods: A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Results: Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Conclusions: Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease. PMID:27648122

Symptomatic outcome following laparoscopic Heller's cardiomyotomy with Dor fundoplication versus laparoscopic Heller's cardiomyotomy with angle of His accentuation: results of a randomized controlled trial.

PubMed

Balakrishna, Pavithra; Parshad, Rajinder; Rohila, Jitender; Saraya, Anoop; Makharia, Govind; Sharma, Raju

2015-08-01

The type of anti-reflux procedure to be used as an adjunct to laparoscopic Heller's cardiomyotomy (LHCM) in Achalasia cardia is controversial. We compared Angle of His accentuation and Dor fundoplication in a randomized controlled trial. From May 2010 to October 2013, 62 patients undergoing LHCM were randomized to receive either Dor fundoplication (Dor group) or Angle of His accentuation (AOH group) as an anti-reflux procedure. Symptomatic outcome was evaluated using modified Mellow and Pinkas scale for dysphagia and modified DeMeester's score for regurgitation and heartburn. Achalasia-specific quality-of-life (QOL) questionnaire was used to assess quality of life. The primary outcome was symptomatic relief and the secondary outcome was postoperative heartburn. Statistical analysis was done using SPSS software. All the procedures were completed laparoscopically with no mortality. Morbidity was similar in the two groups (6.4 %). Median operative time was higher in Dor group (170 vs 130 min). At a median follow-up of 21 months relief of dysphagia, regurgitation, and heartburn was seen in 87, 90.3, and 90.3 % patients in Dor group versus 93.5, 96.7, and 77.4 % in AOH group patients with significant improvement in symptom scores. Improvement was similar in both groups with no statistically significant difference in the symptom scores (p = 0.48 for dysphagia, p = 0.37 for regurgitation, and p = 0.19 for heartburn). The QOL improved in both groups [62.3 to 12.3 (p = 0.02) in Dor group and 63.9-13 (p = 0.02) in AOH group] with no statistically significant difference between the two groups (p = 0.96). There was no statistically significant difference in the postoperative heartburn between the two groups (p = 0.19). Laparoscopic Heller's cardiomyotomy with either Angle of His accentuation or Dor fundoplication leads to similar improvement in symptoms and quality of life.

Phloretin ameliorates 2-chlorohexadecanal-mediated brain microvascular endothelial cell dysfunction in vitro

PubMed Central

Üllen, Andreas; Fauler, Günter; Bernhart, Eva; Nusshold, Christoph; Reicher, Helga; Leis, Hans-Jörg; Malle, Ernst; Sattler, Wolfgang

2012-01-01

2-Chlorohexadecanal (2-ClHDA), a chlorinated fatty aldehyde, is formed via attack on ether-phospholipids by hypochlorous acid (HOCl) that is generated by the myeloperoxidase–hydrogen peroxide–chloride system of activated leukocytes. 2-ClHDA levels are elevated in atherosclerotic lesions, myocardial infarction, and neuroinflammation. Neuroinflammatory conditions are accompanied by accumulation of neutrophils (an ample source of myeloperoxidase) in the brain. Microvessel damage by inflammatory mediators and/or reactive oxidants can induce blood–brain barrier (BBB) dysfunction, a pathological condition leading to cerebral edema, brain hemorrhage, and neuronal death. In this in vitro study we investigated the impact of 2-ClHDA on brain microvascular endothelial cells (BMVEC), which constitute the morphological basis of the BBB. We show that exogenously added 2-ClHDA is subject to rapid uptake and metabolism by BMVEC. Using C16 structural analogues of 2-ClHDA we found that the cytotoxic potential decreases in the following order: 2-ClHDA>hexadecanal>palmitic acid>2-ClHDA-dimethylacetal. 2-ClHDA induces loss of barrier function, mitochondrial dysfunction, apoptosis via activation of caspase 3, and altered intracellular redox balance. Finally we investigated potential protective effects of several natural polyphenols on in vitro BBB function. Of the compounds tested, phloretin almost completely abrogated 2-ClHDA-induced BMVEC barrier dysfunction and cell death. These data suggest that 2-ClHDA has the potential to induce BBB breakdown under inflammatory conditions and that phloretin confers protection in this experimental setting. PMID:22982051

GPER is required for the age-dependent upregulation of the myocardial endothelin system.

PubMed

Meyer, Matthias R; Fredette, Natalie C; Sharma, Geetanjali; Barton, Matthias; Prossnitz, Eric R

2016-08-15

Cardiac aging is associated with progressive structural changes and functional impairment, such as left ventricular hypertrophy, fibrosis and diastolic dysfunction. Aging also increases myocardial activity of endothelin-1 (ET-1), a multifunctional peptide with growth-promoting and pro-fibrotic activity. Because the G protein-coupled estrogen receptor (GPER) regulates vascular responsiveness to ET-1, we investigated whether GPER also plays a role in the regulation of the myocardial endothelin system with aging. Young (4month-old) and aged (24month-old) wild-type and Gper-deficient (Gper(-/-)) mice were studied. Gene expression levels of prepro-ET-1, endothelin converting enzymes ECE-1 and ECE-2, and endothelin ETA and ETB receptors were determined by qPCR in left ventricular myocardium. Aging markedly increased steady-state mRNA expression levels of ECE-1, ECE-2, ETA and ETB receptors (each p<0.001 vs. young mice). Deletion of Gper inhibited the age-dependent increase in ECE-2 and ETB receptor mRNA levels (57% and 40% reduction, respectively, each p<0.01 vs. wild-type mice), whereas gene expression of prepro-ET-1, ECE-1, and the ETA receptor was unaffected in Gper(-/-) mice. We identified a novel regulatory mechanism through which the endogenous Gper facilitates the age-dependent increase in myocardial expression of ECE-2 and the ETB receptor, which is compatible with an activating role of GPER for the local endothelin system with aging. Targeting GPER signaling by selective antagonists may therefore be considered a new therapeutic approach to reduce age-dependent increased ET-1 activity and the associated development of left ventricular hypertrophy, fibrosis and heart failure. Copyright © 2016 Elsevier Inc. All rights reserved.

Myocardial Injury Is Distinguished from Stable Angina by a Set of Candidate Plasma Biomarkers Identified Using iTRAQ/MRM-Based Approach.

PubMed

Cheow, Esther Sok Hwee; Cheng, Woo Chin; Yap, Terence; Dutta, Bamaprasad; Lee, Chuen Neng; Kleijn, Dominique P V de; Sorokin, Vitaly; Sze, Siu Kwan

2018-01-05

The lack of precise biomarkers that identify patients at risk for myocardial injury and stable angina delays administration of optimal therapy. Hence, the search for noninvasive biomarkers that could accurately stratify patients with impending heart attack, from patients with stable coronary artery disease (CAD), is urgently needed in the clinic. Herein, we performed comparative quantitative proteomics on whole plasma sampled from patients with stable angina (NMI), acute myocardial infarction (MI), and healthy control subjects (Ctrl). We detected a total of 371 proteins with high confidence (FDR < 1%, p < 0.05) including 53 preliminary biomarkers that displayed ≥2-fold modulated expression in patients with CAD (27 associated with atherosclerotic stable angina, 26 with myocardial injury). In the verification phase, we used label-free LC-MRM-MS-based targeted method to verify the preliminary biomarkers in pooled plasma, excluded peptides that were poorly distinguished from background, and performed further validation of the remaining candidates in 49 individual plasma samples. Using this approach, we identified a final panel of eight novel candidate biomarkers that were significantly modulated in CAD (p < 0.05) including proteins associated with atherosclerotic stable angina that were implicated in endothelial dysfunction (F10 and MST1), proteins associated with myocardial injury reportedly involved in plaque destabilization (SERPINA3, CPN2, LUM), and in tissue protection/repair mechanisms (ORM2, ACTG1, NAGLU). Taken together, our data showed that candidate biomarkers with potential diagnostic values can be successfully detected in nondepleted human plasma using an iTRAQ/MRM-based discovery-validation approach and demonstrated the plausible clinical utility of the proposed panel in discriminating atherosclerotic stable angina from myocardial injury in the studied cohort.

Effect of beta-adrenergic blockade with timolol on myocardial blood flow during exercise after myocardial infarction in the dog.

PubMed

Herzog, C A; Aeppli, D P; Bache, R J

1984-12-01

The effect of beta-adrenergic blockade with timolol (40 micrograms/kg) on myocardial blood flow during rest and graded treadmill exercise was assessed in 12 chronically instrumented dogs 10 to 14 days after myocardial infarction was produced by acute left circumflex coronary artery occlusion. During exercise at comparable external work loads, the heart rate-systolic blood pressure product was significantly decreased after timilol, with concomitant reductions of myocardial blood flow in normal, border and central ischemic areas (p less than 0.001) and increases in subendocardial/subepicardial blood flow ratios (p less than 0.05). In addition to the blunted chronotropic response to exercise, timolol exerted an effect on myocardial blood flow that was not explained by changes in heart rate or blood pressure. At comparable rate-pressure products during exercise, total myocardial blood flow was 24% lower after timolol (p less than 0.02) and flow was redistributed from subepicardium to subendocardium in all myocardial regions. Thus, timolol altered myocardial blood flow during exercise by two separate mechanisms: a negative chronotropic effect, and a significant selective reduction of subepicardial perfusion independent of changes in heart rate or blood pressure with transmural redistribution of flow toward the subendocardium.

[Myocardial viability: update in nuclear cardiology].

PubMed

Vallejo, Enrique

2007-01-01

Evaluation of myocardial viability with the aid of radionuclides, is a technique that offers reliable, reproducible information, with an attractive cost-benefit relationship, in the study of the myocardial viability, integrating cardiac molecular, metabolic, and functional aspects. Nowadays, coronary risk stratification in post-myocardial infarction patients pretends to locate them as low-, intermediate, and high risk-subjects that can suffer cardiovascular complications in the very near future. Low-risk patients are characterized by a cardiac-related mortality below 1%, whereas high-risk mortality is greater than 3%. Because of clinical complications following a myocardial infarction are observed during the first month of evolution, clinical guidelines suggest to evaluate the cardiovascular risk before hospital discharge.

Imaging of Myocardial Fatty Acid Oxidation

PubMed Central

Mather, Kieren J; DeGrado, Tim

2016-01-01

Myocardial fuel selection is a key feature of the health and function of the heart, with clear links between myocardial function and fuel selection and important impacts of fuel selection on ischemia tolerance. Radiopharmaceuticals provide uniquely valuable tools for in vivo, non-invasive assessment of these aspects of cardiac function and metabolism. Here we review the landscape of imaging probes developed to provide noninvasive assessment of myocardial fatty acid oxidation (MFAO). Also, we review the state of current knowledge that myocardial fatty acid imaging has helped establish of static and dynamic fuel selection that characterizes cardiac and cardiometabolic disease and the interplay between fuel selection and various aspects of cardiac function. PMID:26923433

Calpain inhibition preserves myocardial structure and function following myocardial infarction.

PubMed

Mani, Santhosh K; Balasubramanian, Sundaravadivel; Zavadzkas, Juozas A; Jeffords, Laura B; Rivers, William T; Zile, Michael R; Mukherjee, Rupak; Spinale, Francis G; Kuppuswamy, Dhandapani

2009-11-01

Cardiac pathology, such as myocardial infarction (MI), activates intracellular proteases that often trigger programmed cell death and contribute to maladaptive changes in myocardial structure and function. To test whether inhibition of calpain, a Ca(2+)-dependent cysteine protease, would prevent these changes, we used a mouse MI model. Calpeptin, an aldehydic inhibitor of calpain, was intravenously administered at 0.5 mg/kg body wt before MI induction and then at the same dose subcutaneously once per day. Both calpeptin-treated (n = 6) and untreated (n = 6) MI mice were used to study changes in myocardial structure and function after 4 days of MI, where end-diastolic volume (EDV) and left ventricular ejection fraction (EF) were measured by echocardiography. Calpain activation and programmed cell death were measured by immunohistochemistry, Western blotting, and TdT-mediated dUTP nick-end labeling (TUNEL). In MI mice, calpeptin treatment resulted in a significant improvement in EF [EF decreased from 67 + or - 2% pre-MI to 30 + or - 4% with MI only vs. 41 + or - 2% with MI + calpeptin] and attenuated the increase in EDV [EDV increased from 42 + or - 2 microl pre-MI to 73 + or - 4 microl with MI only vs. 55 + or - 4 microl with MI + calpeptin]. Furthermore, calpeptin treatment resulted in marked reduction in calpain- and caspase-3-associated changes and TUNEL staining. These studies indicate that calpain contributes to MI-induced alterations in myocardial structure and function and that it could be a potential therapeutic target in treating MI patients.

Morphological aspects of myocardial bridges.

PubMed

Lujinović, Almira; Kulenović, Amela; Kapur, Eldan; Gojak, Refet

2013-11-01

Although some myocardial bridges can be asymptomatic, their presence often causes coronary disease either through direct compression of the "tunnel" segment or through stimulation and accelerated development of atherosclerosis in the segment proximally to the myocardial bridge. The studied material contained 30 human hearts received from the Department of Anatomy. The hearts were preserved 3 to 5 days in 10% formalin solution. Thereafter, the fatty tissue was removed and arterial blood vessels prepared by careful dissection with special reference to the presence of the myocardial bridges. Length and thickness of the bridges were measured by the precise electronic caliper. The angle between the myocardial bridge fibre axis and other axis of the crossed blood vessel was measured by a goniometer. The presence of the bridges was confirmed in 53.33% of the researched material, most frequently (43.33%) above the anterior interventricular branch. The mean length of the bridges was 14.64 ± 9.03 mm and the mean thickness was 1.23 ± 1.32 mm. Myocardial bridge fibres pass over the descending blood vessel at the angle of 10-90 degrees. The results obtained on a limited sample suggest that the muscular index of myocardial bridge is the highest for bridges located on RIA, but that the difference is not significant in relation to bridges located on other branches. The results obtained suggest that bridges located on other branches, not only those on RIA, could have a great contractive power and, consequently, a great compressive force, which would be exerted on the wall of a crossed blood vessel.

Nitrogen-13-labeled ammonia for myocardial imaging.

PubMed

Walsh, W F; Fill, H R; Harper, P V

1977-01-01

Cyclotron-produced nitrogen-13 (half-life 10 min), as labeled ammonia (13NH4+), has been evaluated as a myocardial perfusion imaging agent. The regional myocardial uptake of 13NH4+ has been shown to be proportional to regional tissue perfusion in animal studies. Intravenously administered 13NH4+ is rapidly cleared from the circulation, being extracted by the liver (15%), lungs, myocardium (2%-4%), brain, kidney, and bladder. Myocardial ammonia is metabolized mainly to glutamine via the glutamine synthetase pathway. Pulmonary uptake is substantial, but usually transient, except in smokers where clearance may be delayed. The position annihilation irradiation (511 keV) of 13N may be imaged with a scintillation camera, using either a specially designed tungsten collimator or a pinhole collimator. After early technical problems with collimation and the production method of 13NH4+ were overcome, reproducible high quality myocardial images were consistently obtained. The normal myocardial image was established to be of a homogeneous "doughnut" configuration. Imaging studies performed in patients with varying manifestations of ischemic and valvular heart disease showed a high incidence of localized perfusion defects, especially in patients with acute myocardial infarction. Sequential studies at short intervals in patients with acute infarction showed correlation between alterations in regional perfusion and the clinical course of the patient. It is concluded that myocardial imaging with 13NH4+ and a scintillation camera provides a valid and noninvasive means of assessing regional myocardial perfusion. This method is especially suitable for sequential studies of acute cardiac patients at short intervals. Coincidence imaging of the 511 keV annihilation irradiation provides a tomographic and potentially quantitative assessment of the regional myocardial uptake of 13NH4+.

Hot shot induction and reperfusion with a specific blocker of the es-ENT1 nucleoside transporter before and after hypothermic cardioplegia abolishes myocardial stunning in acutely ischemic hearts despite metabolic derangement: Hot shot drug delivery before hypothermic cardioplegia

PubMed Central

Abd-Elfattah, Anwar Saad; Tuchy, Gert E.; Jessen, Michael E.; Salter, David R.; Goldstein, Jacques P.; Brunsting, Louis A.; Wechsler, Andrew S.

2013-01-01

Objective Simultaneous inhibition of the cardiac equilibrative-p-nitrobenzylthioinosine (NBMPR)–sensitive (es) type of the equilibrative nucleoside transport 1 (ENT1) nucleoside transporter, with NBMPR, and adenosine deaminase, with erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA), prevents release of myocardial purines and attenuates myocardial stunning and fibrillation in canine models of warm ischemia and reperfusion. It is not known whether prolonged administration of hypothermic cardioplegia influences purine release and EHNA/NBMPR-mediated cardioprotection in acutely ischemic hearts. Methods Anesthetized dogs (n = 46), which underwent normothermic aortic crossclamping for 20 minutes on-pump, were divided to determine (1) purine release with induction of intermittent antegrade or continuous retrograde hypothermic cardioplegia and reperfusion, (2) the effects of postischemic treatment with 100 µM EHNA and 25 µM NBMPR on purine release and global functional recovery, and (3) whether a hot shot and reperfusion with EHNA/NBMPR inhibits purine release and attenuates ventricular dysfunction of ischemic hearts. Myocardial biopsies and coronary sinus effluents were obtained and analyzed using high-performance liquid chromatography. Results Warm ischemia depleted myocardial adenosine triphosphate and elevated purines (ie, inosine > adenosine) as markers of ischemia. Induction of intermittent antegrade or continuous retrograde hypothermic (4°C) cardioplegia releases purines until the heart becomes cold (<20°C). During reperfusion, the levels of hypoxanthine and xanthine (free radical substrates) were >90% of purines in coronary sinus effluent. Reperfusion with EHNA/NBMPR abolished ventricular dysfunction in acutely ischemic hearts with and without a hot shot and hypothermic cardioplegic arrest. Conclusions Induction of hypothermic cardioplegia releases purines from ischemic hearts until they become cold, whereas reperfusion induces massive purine release and myocardial

Subject-specific left ventricular dysfunction modeling using composite material mechanics approach

NASA Astrophysics Data System (ADS)

Haddad, Seyed Mohammad Hassan; Karami, Elham; Samani, Abbas

2017-03-01

Diverse cardiac conditions such as myocardial infarction and hypertension can lead to diastolic dysfunction as a prevalent cardiac condition. Diastolic dysfunctions can be diagnosed through different adverse mechanisms such as abnormal left ventricle (LV) relaxation, filling, and diastolic stiffness. This paper is geared towards evaluating diastolic stiffness and measuring the LV blood pressure non-invasively. Diastolic stiffness is an important parameter which can be exploited for more accurate diagnosis of diastolic dysfunction. For this purpose, a finite element (FE) LV mechanical model, which works based on a novel composite material model of the cardiac tissue, was utilized. Here, this model was tested for inversion-based applications where it was applied for estimating the cardiac tissue passive stiffness mechanical properties as well as diastolic LV blood pressure. To this end, the model was applied to simulate diastolic inflation of the human LV. The start-diastolic LV geometry was obtained from MR image data segmentation of a healthy human volunteer. The obtained LV geometry was discretized into a FE mesh before FE simulation was conducted. The LV tissue stiffness and diastolic LV blood pressure were adjusted through optimization to achieve the best match between the calculated LV geometry and the one obtained from imaging data. The performance of the LV mechanical simulations using the optimal values of tissue stiffness and blood pressure was validated by comparing the geometrical parameters of the dilated LV model as well as the stress and strain distributions through the LV model with available measurements reported on the LV dilation.

Increase in parasympathetic tone by pyridostigmine prevents ventricular dysfunction during the onset of heart failure.

PubMed

Lataro, Renata M; Silva, Carlos A A; Fazan, Rubens; Rossi, Marcos A; Prado, Cibele M; Godinho, Rosely O; Salgado, Helio C

2013-10-15

Heart failure (HF) is characterized by elevated sympathetic activity and reduced parasympathetic control of the heart. Experimental evidence suggests that the increase in parasympathetic function can be a therapeutic alternative to slow HF evolution. The parasympathetic neurotransmission can be improved by acetylcholinesterase inhibition. We investigated the long-term (4 wk) effects of the acetylcholinesterase inhibitor pyridostigmine on sympathovagal balance, cardiac remodeling, and cardiac function in the onset of HF following myocardial infarction. Myocardial infarction was elicited in adult male Wistar rats. After 4 wk of pyridostigmine administration, per os, methylatropine and propranolol were used to evaluate the cardiac sympathovagal balance. The tachycardic response caused by methylatropine was considered to be the vagal tone, whereas the bradycardic response caused by propranolol was considered to be the sympathetic tone. In conscious HF rats, pyridostigmine reduced the basal heart rate, increased vagal, and reduced sympathetic control of heart rate. Pyridostigmine reduced the myocyte diameter and collagen density of the surviving left ventricle. Pyridostigmine also increased vascular endothelial growth factor protein in the left ventricle, suggesting myocardial angiogenesis. Cardiac function was assessed by means of the pressure-volume conductance catheter system. HF rats treated with pyridostigmine exhibited a higher stroke volume, ejection fraction, cardiac output, and contractility of the left ventricle. It was demonstrated that the long-term administration of pyridostigmine started right after coronary artery ligation augmented cardiac vagal and reduced sympathetic tone, attenuating cardiac remodeling and left ventricular dysfunction during the progression of HF in rats.

Myocardial perfusion imaging with PET

PubMed Central

Nakazato, Ryo; Berman, Daniel S; Alexanderson, Erick; Slomka, Piotr

2013-01-01

PET-myocardial perfusion imaging (MPI) allows accurate measurement of myocardial perfusion, absolute myocardial blood flow and function at stress and rest in a single study session performed in approximately 30 min. Various PET tracers are available for MPI, and rubidium-82 or nitrogen-13-ammonia is most commonly used. In addition, a new fluorine-18-based PET-MPI tracer is currently being evaluated. Relative quantification of PET perfusion images shows very high diagnostic accuracy for detection of obstructive coronary artery disease. Dynamic myocardial blood flow analysis has demonstrated additional prognostic value beyond relative perfusion imaging. Patient radiation dose can be reduced and image quality can be improved with latest advances in PET/CT equipment. Simultaneous assessment of both anatomy and perfusion by hybrid PET/CT can result in improved diagnostic accuracy. Compared with SPECT-MPI, PET-MPI provides higher diagnostic accuracy, using lower radiation doses during a shorter examination time period for the detection of coronary artery disease. PMID:23671459

Detecting Myocardial Ischemia With 99mTechnetium-Tetrofosmin Myocardial Perfusion Imaging in Ischemic Stroke.

PubMed

Giannopoulos, Sotirios; Markoula, Sofia; Sioka, Chrissa; Zouroudi, Sofia; Spiliotopoulou, Maria; Naka, Katerina K; Michalis, Lampros K; Fotopoulos, Andreas; Kyritsis, Athanassios P

2017-10-01

To assess the myocardial status in patients with stroke, employing myocardial perfusion imaging (MPI) with 99m Technetium-tetrofosmin ( 99m Tc-TF)-single-photon emission computed tomography (SPECT). Fifty-two patients with ischemic stroke were subjected to 99m Tc-TF-SPECT MPI within 1 month after stroke occurrence. None of the patients had any history or symptoms of coronary artery disease or other heart disease. Myocardial perfusion imaging was evaluated visually using a 17-segment polar map. Myocardial ischemia (MIS) was defined as present when the summed stress score (SSS) was >4; MIS was defined as mild when SSS was 4 to 8, and moderate/severe with SSS ≥9. Patients with SSS >4 were compared to patients with SSS <4. Parameters such as age, body mass index, waist perimeter, smoking habits, and medical history (diabetes mellitus, dyslipidemia, etc) were evaluated according to MPI results. Myocardial ischemia was present in 32 (62%) of 52 patients with stroke. Among them, 20 (62%) of 32 patients had mild abnormalities and 12 (38%) of 32 had moderate/severe. The age and waist perimeter showed a tendency to relate to severe MIS when patients with SSS >9 were compared to patients with SSS <4. In MPI-positive patients, an age was to be association with SSS, with the oldest age exhibiting the highest SSS ( P = .01). The association of age with SSS remained statistically significant in the multivariate analysis ( P = .04). The study suggested that more than half of patients with stroke without a history of cardiac disease have MIS. Although most of them have mild MIS, we suggest a thorough cardiological evaluation in this group of patients for future prevention of severe myocardial outcome.

Temporomandibular dysfunction

PubMed

Lomas, Jonathan; Gurgenci, Taylan; Jackson, Christopher; Campbell, Duncan

2018-04-01

Orofacial pain is a common presentation in the primary healthcare setting and temporomandibular dysfunction represents one of the major causes. Its aetiology is multifactorial, caused by both masticatory muscle dysfunction and derangement within the temporomandibular joint. The aim of this article is to provide an overview of temporomandibular dysfunction, its management and referral considerations for general practioners. Temporomandibular joint dysfunction affects a large number of adults. Conservative management involving non-pharmacological and pharmacological therapies is effective in the majority of cases.

Cardiovascular disease and cognitive dysfunction in systemic lupus erythematosus.

PubMed

Murray, Sara G; Yazdany, Jinoos; Kaiser, Rachel; Criswell, Lindsey A; Trupin, Laura; Yelin, Edward H; Katz, Patricia P; Julian, Laura J

2012-09-01

Cognitive dysfunction and cardiovascular disease are common and debilitating manifestations of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between cardiovascular events, traditional cardiovascular risk factors, and SLE-specific risk factors as predictors of cognitive dysfunction in a large cohort of participants with SLE. Subjects included 694 participants from the Lupus Outcomes Study (LOS), a longitudinal study of SLE outcomes based on an annual telephone survey querying demographic and clinical variables. The Hopkins Verbal Learning Test-Revised and the Controlled Oral Word Association Test were administered to assess cognitive function. Multiple logistic regression was used to identify cardiovascular events (myocardial infarction, stroke), traditional cardiovascular risk factors (hypertension, hyperlipidemia, diabetes mellitus, obesity, smoking), and SLE-specific risk factors (antiphospholipid antibodies [aPL], disease activity, disease duration) associated with cognitive impairment in year 7 of the LOS. The prevalence of cognitive impairment as measured by verbal memory and verbal fluency metrics was 15%. In adjusted multiple logistic regression analyses, aPL (odds ratio [OR] 2.10, 95% confidence interval [95% CI] 1.3-3.41), hypertension (OR 2.06, 95% CI 1.19-3.56), and a history of stroke (OR 2.27, 95% CI 1.16-4.43) were significantly associated with cognitive dysfunction. In additional analyses evaluating the association between these predictors and severity of cognitive impairment, stroke was significantly more prevalent in participants with severe impairment when compared to those with mild or moderate impairment (P = 0.036). These results suggest that the presence of aPL, hypertension, and stroke are key variables associated with cognitive impairment, which may aid in identification of patients at greatest risk. Copyright © 2012 by the American College of Rheumatology.

Combined baseline and one-month changes in big endothelin-1 and brain natriuretic peptide plasma concentrations predict clinical outcomes in patients with left ventricular dysfunction after acute myocardial infarction: Insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study.

PubMed

Olivier, A; Girerd, N; Michel, J B; Ketelslegers, J M; Fay, R; Vincent, J; Bramlage, P; Pitt, B; Zannad, F; Rossignol, P

2017-08-15

Increased levels of neuro-hormonal biomarkers predict poor prognosis in patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD). The predictive value of repeated (one-month interval) brain natriuretic peptides (BNP) and big-endothelin 1 (BigET-1) measurements were investigated in patients with LVSD after AMI. In a sub-study of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS trial), BNP and BigET-1 were measured at baseline and at 1month in 476 patients. When included in the same Cox regression model, baseline BNP (p=0.0003) and BigET-1 (p=0.026) as well as the relative changes (after 1month) from baseline in BNP (p=0.049) and BigET-1 (p=0.045) were predictive of the composite of cardiovascular death or hospitalization for worsening heart failure. Adding baseline and changes in BigET-1 to baseline and changes in BNP led to a significant increase in prognostic reclassification as assessed by integrated discrimination improvement index (5.0%, p=0.01 for the primary endpoint). Both increased baseline and changes after one month in BigET-1 concentrations were shown to be associated with adverse clinical outcomes, independently from BNP baseline levels and one month changes, in patients after recent AMI complicated with LVSD. This novel result may be of clinical interest since such combined biomarker assessment could improve risk stratification and open new avenues for biomarker-guided targeted therapies. In the present study, we report for the first time in a population of patients with reduced LVEF after AMI and signs or symptoms of congestive HF, that increased baseline values of BNP and BigET-1 as well as a further rise of these markers over the first month after AMI, were independently predictive of future cardiovascular events. This approach may therefore be of clinical interest with the potential of improving risk stratification after AMI with reduced LVEF while

Association of subclinical myocardial injury with arterial stiffness in patients with type 2 diabetes mellitus

PubMed Central

2013-01-01

Objective Type 2 diabetes mellitus (T2DM) is associated with subclinical myocardial injury although the underlying mechanism is uncertain. We postulated that arterial stiffness, endothelial dysfunction and subclinical atherosclerosis may contribute to subclinical myocardial injury in patients with T2DM. Methods Serum high-sensitivity troponin I (hs-TNI) an indicator of myocardial injury, was measured in 100 patients with T2DM without clinical evidence of macrovascular disease and 150 age and gender-matched controls. Elevated hs-TnI was defined as follow (derived from the 99th percentile from controls): Male >11.1 ng/L; female >7.6 ng/L. Measures that may contribute to myocardial damage in patients with T2DM, including brachial-ankle pulse wave velocity (ba-PWV), brachial flow mediated dilatation (FMD) and carotid intima media thickness (IMT), were also assessed. Results The serum level of hs-TNI (5.7±9.2 μg/L vs. 3.2±1.9 μg/L, P< 0.01) and the prevalence of elevated hs-TNI (12% vs. 4%, P = 0.02) were significantly higher in patients with T2DM than controls. Patients with T2DM also had significantly worse ba-PWV (17.98±3.91ms-1 vs. 15.70±2.96 ms-1), brachial FMD (2.6±3.5% vs. 5.5±4.2%, P< 0.01) and carotid IMT (0.96±0.20 mm vs. 0.86±0.14 mm, P< 0.01). In patients with T2DM, hs-TNI was positively correlated with systolic blood pressure (r = 0.31, P<0.01), serum creatinine (r = 0.26, P = 0.01) and ba-PWV (r = 0.34, P< 0.01). Importantly, multiple regression revealed that only ba-PWV was independently associated with hs-TNI (β = 0.25, P = 0.04). Conclusion The results demonstrated an independent association between ba-PWV and hs-TNI in patients with T2DM with no clinical evidence of macrovascular disease. These findings suggest that increased arterial stiffness is closely related to subclinical myocardial injury in patients with T2DM. PMID:23799879

Microvascular autonomic dysfunction may justify false-positive stress myocardial perfusion imaging in patients with liver cirrhosis undergoing liver transplantation.

PubMed

Senzolo, M; Bassanello, M; Graziotto, A; Zucchetta, P; Cillo, U; Maraglino, G; Loreno, M; Bellotto, F; Davià, G; Burra, P

2008-01-01

Up to 15% of liver transplant candidates have asymptomatic coronary artery diseases, which increase the risk of cardiac complications during and after transplantation. The aim of this study was to prospectively investigate the usefulness of an integrated cardiological approach in cirrhotic patients undergoing liver transplantation. Twenty-four consecutive patients undergoing evaluation for liver transplantation were studied by assessing risk factors for coronary artery diseases, electrocardiogram with QTc interval determination, chest X-ray, echocardiography, 24-hour Holter monitor, myocardial perfusion scintigraphy (99mTc)MIBI-GSPECT at rest and after dipyridamole infusion. Cardiac (123)I-metaiodobenzylguanidine (MIBG) scan and coronarography were performed in patients with myocardial perfusion defects. Twenty three of 24 patients underwent successful liver transplantation; one patient died on the waiting list. Before liver transplantation, 29% of patients were diabetic and 41% were smokers. Eleven of 24 patients had a prolonged QTc interval, and 3/24 had positive myocardioscintigraphy after dipyridamole infusion: in two coronarography was negative, while the (123)I-MIBG washout was altered. No cardiac events were recorded during the short-and long-term follow-up after surgery. Predictive value of positive cardiac (99mTc)MIBI-GSPECT in patients with liver cirrhosis is low, and this may be due to alterations of cardiac microvascular tone as showed by cardiac (123)I-MIBG scan.

Role of Myocardial Collagen in Severe Aortic Stenosis With Preserved Ejection Fraction and Symptoms of Heart Failure.

PubMed

Echegaray, Kattalin; Andreu, Ion; Lazkano, Ane; Villanueva, Iñaki; Sáenz, Alberto; Elizalde, María Reyes; Echeverría, Tomás; López, Begoña; Garro, Asier; González, Arantxa; Zubillaga, Elena; Solla, Itziar; Sanz, Iñaki; González, Jesús; Elósegui-Artola, Alberto; Roca-Cusachs, Pere; Díez, Javier; Ravassa, Susana; Querejeta, Ramón

2017-10-01

We investigated the anatomical localization, biomechanical properties, and molecular phenotype of myocardial collagen tissue in 40 patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure. Two transmural biopsies were taken from the left ventricular free wall. Mysial and nonmysial regions of the collagen network were analyzed. Myocardial collagen volume fraction (CVF) was measured by picrosirius red staining. Young's elastic modulus (YEM) was measured by atomic force microscopy in decellularized slices to assess stiffness. Collagen types I and III were measured as C I VF and C III VF, respectively, by confocal microscopy in areas with YEM evaluation. Compared with controls, patients exhibited increased mysial and nonmysial CVF and nonmysial:mysial CVF ratio (P < .05). In patients, nonmysial CVF (r = 0.330; P = .046) and the nonmysial:mysial CVF ratio (r = 0.419; P = .012) were directly correlated with the ratio of maximal early transmitral flow velocity in diastole to early mitral annulus velocity in diastole. Both the C I VF:C III VF ratio and YEM were increased (P ≤ .001) in nonmysial regions compared with mysial regions in patients, with a direct correlation (r = 0.895; P < .001) between them. These findings suggest that, in patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure, diastolic dysfunction is associated with increased nonmysial deposition of collagen, predominantly type I, resulting in increased extracellular matrix stiffness. Therefore, the characteristics of collagen tissue may contribute to diastolic dysfunction in these patients. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Myocardial Blood Volume Is Associated with Myocardial Oxygen Consumption: An Experimental Study with CMR in a Canine Model

PubMed Central

McCommis, Kyle S.; Zhang, Haosen; Goldstein, Thomas A.; Misselwitz, Bernd; Abendschein, Dana R.; Gropler, Robert J.; Zheng, Jie

2009-01-01

OBJECTIVES To evaluate the feasibility of cardiovascular MR (CMR) to determine regional myocardial perfusion and O2 metabolism, and assess the role of myocardial blood volume (MBV) on oxygen supply. BACKGROUND Coronary artery disease presents as an imbalance of myocardial oxygen supply and demand. We have developed relevant CMR methods to determine the relationship of myocardial blood flow (MBF) and MBV to oxygen consumption (MVO2) during pharmacologic hyperemia. METHODS Twenty-one mongrel dogs were studied with varying stenosis severities imposed on the proximal left anterior descending (LAD) coronary artery. MBF and MBV were determined by CMR first-pass perfusion, while the oxygen extraction fraction (OEF) and MVO2 were determined by the myocardial Blood-Oxygen-Level-Dependent (BOLD) effect and Fick’s law, respectively. MR imaging was performed at rest, and during either dipyridamole-induced vasodilation or dobutamine-induced hyperemia. Regional differences in myocardial perfusion and oxygenation were then evaluated. RESULTS Dipyridamole and dobutamine both led to 145–200% increases in MBF and 50–80% increases in MBV in normal perfused myocardium. As expected, MVO2 increased more significantly with dobutamine (~175%) than dipyridamole (~40%). Coronary stenosis resulted in an attenuation of MBF, MBV, and MVO2 in both the LAD-subtended stenosis region and the left circumflex subtended remote region. Liner regression analysis showed that MBV reserve appears to be more correlated with MVO2 reserve during dobutamine stress than MBF reserve, particularly in the stenotic regions. Conversely, MBF reserve appears to be more correlated with MVO2 reserve during dipyridamole, although neither of these differences was significant. CONCLUSIONS Noninvasive evaluation of both myocardial perfusion and oxygenation by CMR facilitates direct monitoring of regional myocardial ischemia and provides a valuable tool for better understanding microvascular pathophysiology. These

Sgarbossa criteria and acute myocardial infarction.

PubMed

Alang, Neha; Bathina, Jaya; Kranis, Mark; Angelis, Dimitrios

2010-01-01

Diagnosis of acute ST-elevation myocardial infarction in the presence of left bundle branch block is difficult. present a case of acute myocardial infarction with LBBB diagnosed and treated using the Sgarbossa criteria.

Garlic-Derived Organic Polysulfides and Myocardial Protection123

PubMed Central

Bradley, Jessica M; Organ, Chelsea L; Lefer, David J

2016-01-01

For centuries, garlic has been shown to exert substantial medicinal effects and is considered to be one of the best disease-preventative foods. Diet is important in the maintenance of health and prevention of many diseases including cardiovascular disease (CVD). Preclinical and clinical evidence has shown that garlic reduces risks associated with CVD by lowering cholesterol, inhibiting platelet aggregation, and lowering blood pressure. In recent years, emerging evidence has shown that hydrogen sulfide (H2S) has cardioprotective and cytoprotective properties. The active metabolite in garlic, allicin, is readily degraded into organic diallyl polysulfides that are potent H2S donors in the presence of thiols. Preclinical studies have shown that enhancement of endogenous H2S has an impact on vascular reactivity. In CVD models, the administration of H2S prevents myocardial injury and dysfunction. It is hypothesized that these beneficial effects of garlic may be mediated by H2S-dependent mechanisms. This review evaluates the current knowledge concerning the cardioprotective effects of garlic-derived diallyl polysulfides. PMID:26764335

(-) Epicatechin prevents alterations in lysosomal glycohydrolases, cathepsins and reduces myocardial infarct size in isoproterenol-induced myocardial infarcted rats.

PubMed

Prince, Ponnian Stanely Mainzen

2013-04-15

The preventive effects of (-) epicatechin on oxidative stress, cardiac mitochondrial damage, altered membrane bound adenosine triphosphatases and minerals were reported previously in isoproterenol-induced myocardial infarction model. Leakage of lysosomal glycohydrolases and cathepsins play an important role in the pathology of myocardial infarction. This study was aimed to evaluate the preventive effects of (-) epicatechin on alterations in lysosomal glycohydrolases, cathepsins and myocardial infarct size in isoproterenol-induced myocardial infarcted rats. Male albino Wistar rats were pretreated with (-) epicatechin (20mg/kg body weight) daily for a period of 21 days. After the pretreatment period, isoproterenol (100mg/kg body weight) was injected subcutaneously into the rats at an interval of 24h for two days to induce myocardial infarction. The levels of serum cardiac troponin-I and the activities of serum and heart lysosomal enzymes (β-glucuronidase, β-N-acetyl glucosaminidase, β-galactosidase, cathepsin-B and cathepsin-D) were increased significantly (P<0.05) and the activities of β-glucuronidase and cathepsin-D in the heart lysosomal fractions were significantly (P<0.05) decreased in isoproterenol-induced myocardial infarcted rats. The in vitro study revealed the potent antioxidant action of (-) epicatechin. Pretreatment with (-) epicatechin daily for a period of 21 days prevented the leakage of cardiac marker, lysosomal glycohydrolases, cathepsins, and reduced infarct size, thereby protecting the lysosomal membranes in isoproterenol-induced myocardial infarcted rats, by virtue of its membrane stabilizing property. Copyright © 2013 Elsevier B.V. All rights reserved.

Increased myocardial short-range forces in a rodent model of diabetes reflect elevated content of β myosin heavy chain.

PubMed

Chung, Charles S; Mitov, Mihail I; Callahan, Leigh Ann; Campbell, Kenneth S

2014-06-15

Diastolic dysfunction is a clinically significant problem for patients with diabetes and often reflects increased ventricular stiffness. Attached cross-bridges contribute to myocardial stiffness and produce short-range forces, but it is not yet known whether these forces are altered in diabetes. In this study, we tested the hypothesis that cross-bridge-based short-range forces are increased in the streptozotocin (STZ) induced rat model of type 1 diabetes. Chemically permeabilized myocardial preparations were obtained from 12week old rats that had been injected with STZ or vehicle 4weeks earlier, and activated in solutions with pCa (=-log10[Ca(2+)]) values ranging from 9.0 to 4.5. The short-range forces elicited by controlled length changes were ∼67% greater in the samples from the diabetic rats than in the control preparations. This change was mostly due to an increased elastic limit (the length change at the peak short-range force) as opposed to increased passive muscle stiffness. The STZ-induced increase in short-ranges forces is thus unlikely to reflect changes to titin and/or collagen filaments. Gel electrophoresis showed that STZ increased the relative expression of β myosin heavy chain. This molecular mechanism can explain the increased short-ranges forces observed in the diabetic tissue if β myosin molecules remain bound between the filaments for longer durations than α molecules during imposed movements. These results suggest that interventions that decrease myosin attachment times may be useful treatments for diastolic dysfunction associated with diabetes. Copyright © 2013 Elsevier Inc. All rights reserved.

Quantitative Myocardial Perfusion Imaging Versus Visual Analysis in Diagnosing Myocardial Ischemia: A CE-MARC Substudy.

PubMed

Biglands, John D; Ibraheem, Montasir; Magee, Derek R; Radjenovic, Aleksandra; Plein, Sven; Greenwood, John P

2018-05-01

This study sought to compare the diagnostic accuracy of visual and quantitative analyses of myocardial perfusion cardiovascular magnetic resonance against a reference standard of quantitative coronary angiography. Visual analysis of perfusion cardiovascular magnetic resonance studies for assessing myocardial perfusion has been shown to have high diagnostic accuracy for coronary artery disease. However, only a few small studies have assessed the diagnostic accuracy of quantitative myocardial perfusion. This retrospective study included 128 patients randomly selected from the CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) study population such that the distribution of risk factors and disease status was proportionate to the full population. Visual analysis results of cardiovascular magnetic resonance perfusion images, by consensus of 2 expert readers, were taken from the original study reports. Quantitative myocardial blood flow estimates were obtained using Fermi-constrained deconvolution. The reference standard for myocardial ischemia was a quantitative coronary x-ray angiogram stenosis severity of ≥70% diameter in any coronary artery of >2 mm diameter, or ≥50% in the left main stem. Diagnostic performance was calculated using receiver-operating characteristic curve analysis. The area under the curve for visual analysis was 0.88 (95% confidence interval: 0.81 to 0.95) with a sensitivity of 81.0% (95% confidence interval: 69.1% to 92.8%) and specificity of 86.0% (95% confidence interval: 78.7% to 93.4%). For quantitative stress myocardial blood flow the area under the curve was 0.89 (95% confidence interval: 0.83 to 0.96) with a sensitivity of 87.5% (95% confidence interval: 77.3% to 97.7%) and specificity of 84.5% (95% confidence interval: 76.8% to 92.3%). There was no statistically significant difference between the diagnostic performance of quantitative and visual analyses (p = 0.72). Incorporating rest myocardial

Gender Differences in Left Ventricular Function Following Percutaneous Coronary Intervention for First Anterior Wall ST-Segment Elevation Myocardial Infarction.

PubMed

Weissler-Snir, Adaya; Kornowski, Ran; Sagie, Alexander; Vaknin-Assa, Hana; Perl, Leor; Porter, Avital; Lev, Eli; Assali, Abid

2014-11-15

Little is known regarding gender differences in left ventricular (LV) function after anterior wall ST-segment elevation myocardial infarction (STEMI), despite it being a major determinant of patients' morbidity and mortality. We therefore sought to investigate the impact of gender on LV function after primary percutaneous coronary intervention (PCI) for first anterior wall STEMI. Seven hundred eighty-nine consecutive patients (625 men) with first anterior STEMI were included in the analysis. All patients underwent an echocardiographic study within 48 hours of PCI. Women were older and more likely to have diabetes, hypertension, chronic renal failure, and a higher Killip score. Women had prolonged ischemic time, which was driven by prolonged symptom-to-presentation time (2.75 [interquartile range 1.5 to 4] vs 2 [interquartile range 1 to 3.5] hours, p = 0.005). A higher percentage of women had moderate or worse LV dysfunction (LV ejection fraction <40%; 61.6% vs 48%, p = 0.002). In a univariable analysis female gender was associated with moderate or worse LV function (p = 0.002). However, after accounting for variable baseline risk profiles between the 2 groups using multivariable and propensity score techniques, ischemic time >3.5 hours, leukocytosis, and pre-PCI Thrombolysis In Myocardial Infarction flow grade <2 were independent predictors of moderate or worse LV dysfunction, whereas female gender was not. Data on LV function recovery at 6 months, which were available for 45% of female and male patients with moderate or worse LV dysfunction early after PCI, showed no significant gender related difference in LV function recovery. In conclusion, women undergoing PCI for the first event of anterior STEMI demonstrate worse LV function than that of men, which might be partially attributed to delay in presentation. Hence greater efforts should be devoted to increasing women's awareness of cardiac symptoms during the prehospital course of STEMI. Copyright © 2014

[Adenoviral short hairpin RNA targeting phosphodiesterase 5 attenuates cardiac remodeling and cardiac dysfunction following myocardial infarction in mice].

PubMed

Zhang, Jian; Jin, Zhe; Li, Longhu; Gang, Li; Yu, Qin; Wang, Meilan; Song, Ailin; Hong, Bingzhe

2014-04-01

To observe the impact of PDE5shRNA on cardiac remodeling and heart function following myocardial infarction in mice. Myocardial infarction (MI) was induced in mice by left coronary artery ligation. Mice were randomly assigned to sham group (n = 6), PDE5shRNA group (n = 12), common adenovirus group (n = 15) and DMEM group (n = 8). Four weeks post-MI, the survival rate was evaluated. Cardiac function was examined by echocardiography. HE staining and Masson staining were used to evaluate the myocardial infarction size and fibrosis. The number of blood vessels was evaluated by immunohistochemistry, PDE5 protein expression in the left ventricular was detected using Western blot, level of cGMP or PKG activity in the left ventricle was evaluated with ELISA. Four weeks post-MI, all mice survived in the sham group, 3(37%) mice died in the DMEM group, 1 (8%) died in the PDE5shRNA group and 5 died in the common adenovirus group (33%). Infarct size was significantly reduced in PDE5shRNA group compared with the common adenovirus group and DMEM group [(25.4 ± 2.9)% vs. (42.0 ± 3.2)% and (43.4 ± 2.6) %, P < 0.05]. Cardiac function was significantly improved in PDE5shRNA group compared to common adenovirus group and DMEM group[LVFS: (21.1 ± 3.7)% vs. (14.2 ± 2.9)% and (14.22 ± 2.91)%, all P < 0.05; LVEF: (48.2 ± 7.1)% vs. (34.6 ± 6.2)% and (38.1 ± 2.8)%, all P < 0.05; LVESD: (3.87 ± 0.45) mm vs.(4.91 ± 0.62) mm and (4.63 ± 0.37) mm, all P < 0.05]. The blood vessel density was also higher in PDE5shRNA group compared with common adenovirus group (infarct area:14.3 ± 2.0 vs. 6.6 ± 1.2, P < 0.05; periinfarct area: 23.6 ± 2.1 vs. 13.7 ± 2.4, P < 0.05). Compared with common adenovirus group, level of PDE5 was significantly downregulated and level of cGMP or PKG was significantly upregulated in PDE5shRNA group (all P < 0.05). Present study suggests PDE5shRNA improves cardiac function and attenuates cardiac remodeling through reducing infarction size and cardiac fibrosis

Chronic Kidney Disease and Risk of Presenting with Acute Myocardial Infarction versus Stable Exertional Angina in Adults with Coronary Heart Disease

PubMed Central

Go, Alan S.; Bansal, Nisha; Chandra, Malini; Lathon, Phenius V.; Fortmann, Stephen P.; Iribarren, Carlos; Hsu, Chi-yuan; Hlatky, Mark A.

2011-01-01

Objective To examine whether kidney dysfunction is associated with the type of clinical presentation of coronary heart disease (CHD). Background Reduced kidney function increases risk of developing CHD, but it is not known whether it also influences the acuity of clinical presentation, which has important prognostic implications. Methods We conducted a case-control study of subjects whose first clinical presentation of CHD was either acute myocardial infarction or stable exertional angina between October 2001-December 2003. Glomerular filtration rate (eGFR) before the incident event was estimated using calibrated serum creatinine and the abbreviated MDRD equation. Patient characteristics and use of medications were ascertained from self-report and health plan databases. We used multivariable logistic regression to examine the association of reduced eGFR and CHD presentation. Results We studied 803 adults with incident acute myocardial infarction and 419 adults with incident stable exertional angina who had a baseline eGFR ≤130 ml/min/1.73 m2. Mean eGFR was lower among subjects with acute myocardial infarction compared with stable angina. Compared with eGFR 90–130 ml/min/1.73 m2, we found a strong, graded independent association between reduced eGFR and presenting with acute myocardial infarction: adjusted odds ratio (OR) 1.36 (95% CI: 0.99 to 1.86) for eGFR 60–89 ml/min/1.73 m2, OR 1.55 (0.92 to 2.62) for eGFR 45–59 ml/min/1.73 m2 and OR 3.82 (1.55 to 9.46) for eGFR <45 ml/min/1.73 m2 (P<0.001 for trend). Conclusion eGFR less than 45 ml/min/1.73 m2 is a strong, independent predictor of presenting with acute myocardial infarction versus stable angina as the initial manifestation of CHD. PMID:21958887

Melatonin protects against myocardial hypertrophy induced by lipopolysaccharide.

PubMed

Lu, Qi; Yi, Xin; Cheng, Xiang; Sun, Xiaohui; Yang, Xiangjun

2015-04-01

Melatonin is thought to have the ability of antiatherogenic, antioxidant, and vasodilatory. It is not only a promising protective in acute myocardial infarction but is also a useful tool in the treatment of pathological remodeling. However, its role in myocardial hypertrophy remains unclear. In this study, we investigated the protective effects of melatonin on myocardial hypertrophy induced by lipopolysaccharide (LPS) and to identify their precise mechanisms. The cultured myocardial cell was divided into six groups: control group, LPS group, LPS + ethanol (4%), LPS + melatonin (1.5 mg/ml) group, LPS + melatonin (3 mg/ml) group, and LPS + melatonin (6 mg/ml) group. The morphologic change of myocardial cell was observed by inverted phase contrast microscope. The protein level of myocardial cell was measured by Coomassie brilliant blue protein kit. The secretion level of tumor necrosis factor-α (TNF-α) was evaluated by enzyme-linked immunosorbent assay (ELISA). Ca(2+) transient in Fura-2/AM-loaded cells was measured by Till image system. The expression of Ca(2+)/calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) was measured by Western blot analysis. Our data demonstrated that LPS induced myocardial hypertrophy, promoted the secretion levels of TNF-α, and increased Ca(2+) transient level and the expression of CaMKII and CaN. Administration of melatonin 30 min prior to LPS stimulation dose-dependently attenuated myocardial hypertrophy. In conclusion, the results revealed that melatonin had the potential to protect against myocardial hypertrophy induced by LPS in vitro through downregulation of the TNF-α expression and retains the intracellular Ca(2+) homeostasis.

Cocaine, a risk factor for myocardial infarction.

PubMed

Galasko, G I

1997-06-01

Cocaine usage goes back thousands of years, to the times of the Incas. Over the past 20 years, its use has increased dramatically, especially in America, and adverse cardiovascular reactions to the drug have begun to be reported. The first report of myocardial infarction temporally related to the recreational use of cocaine appeared in 1982. Since then, myocardial infarction has become recognized as the drug's most common cardiovascular consequence, with over 250 cases now documented in the literature. This review discusses the history of cocaine use, its pharmacology, the possible pathological mechanisms underlying the pathogenesis of myocardial ischaemia and infarction, and current ideas on the management of cocaine-induced myocardial infarction.

Impaired left ventricular diastolic function is related to the formation of left ventricular apical thrombus in patients with acute anterior myocardial infarction.

PubMed

Choi, Ung Lim; Park, Jae-Hyeong; Sun, Byung Joo; Oh, Jin Kyung; Seong, Seok Woo; Lee, Jae-Hwan; Choi, Si Wan; Jeong, Jin-Ok; Kwon, In Sun; Seong, In-Whan

2018-05-01

Left ventricular (LV) apical thrombus is a clinically important complication which can cause systemic embolization in patients with anterior acute myocardial infarction (AMI). Systolic dysfunction has been a risk factor for developing LV apical thrombus in AMI patients. However, the role of diastolic dysfunction in the development of LV apical thrombus in these patients is still unknown. We performed this study to evaluate whether diastolic dysfunction can influence the development of LV apical thrombus in anterior AMI patients. We retrospectively analyzed all consecutive anterior AMI patients with available echocardiographic images within 1 month from January 2005 to April 2016. After gathering clinical characteristics from their medical records, systolic and diastolic functions were analyzed from digitally stored echocardiographic images. We included a total of 1045 patients (748 males, mean age 64 ± 12 years) with anterior AMI, and 494 (47%) were diagnosed as STEMI. The incidence of LV apical thrombus was 3.3% (34/1045). The LV apical thrombus group had larger LV diastolic dimension, larger LV diastolic and systolic volumes, and lower LVEF than the no LV thrombus group. The LV apical thrombus group showed higher mitral E velocity over mitral annular E' velocity ratio, an indicator of LV end-diastolic pressure (P < 0.001). In the LV apical thrombus group, the incidence of grade 2 diastolic dysfunction (32 vs 12%, P = 0.001) and grade 3 diastolic dysfunction (26 vs 2%, P < 0.001) were significantly higher than in the no LV apical thrombus group. The presence of more than grade 2 diastolic dysfunction, LVEF and presence of LV apical aneurysm were statistically significant factors associated with LV apical thrombus after the multivariate analysis. In conclusion, along with LV systolic dysfunction and LV apical aneurysm, LV diastolic dysfunction was also related with the presence of LV apical thrombus in patients with anterior AMI.

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.

Visit-to-visit blood pressure variation is associated with outcomes in a U-shaped fashion in patients with myocardial infarction complicated with systolic dysfunction and/or heart failure: findings from the EPHESUS and OPTIMAAL trials.

PubMed

Ferreira, João Pedro; Duarte, Kévin; Pitt, Bertram; Dickstein, Kenneth; McMurray, John J V; Zannad, Faiez; Rossignol, Patrick

2018-04-21

Visit-to-visit office blood pressure variation (BPV) has prognostic implications independent from mean BP across several populations in the cardiovascular field. The association of BPV with outcomes in patients with myocardial infarction (MI) with systolic dysfunction and/or heart failure is yet to be determined. Two independent cohorts were assessed: the EPHESUS and the OPTIMAAL trials with a total of more than 12 000 patients. The primary outcome was all-cause death. BPV was calculated as a coefficient of variation, that is, the ratio of the SD to the mean BP along the postbaseline follow-up. Cox regression models were used to determine the associations between BPV and events. Compared with the middle and lower BPV tertiles, patients in the upper BPV tertile were older, more often women, hypertensive, diabetic, with peripheral artery disease, and had more frequent use of loop diuretics and ACEi/ARBs. They also had lower LVEF, hemoglobin, and eGFR (all P < 0.001). BPV was independently associated with worse prognosis in a U-shaped manner. In the EPHESUS trial, both low and high BPV were associated with higher rates of death (and also cardiovascular death and the composite of cardiovascular death/ cardiovascular hospitalization): adjusted hazard ratio (95% CI) for the outcome of death is 1.99 (1.68-2.36) for high BPV and is 1.60 (1.35-1.90) for low BPV. Similar results were observed in the OPTIMAAL trial population. In two independent cohorts of MI patients with systolic dysfunction and/or heart failure, BPV was associated with worse prognosis in a U-shaped manner independently of the mean BP.

[A case of rupture of the left ventricle free wall with papillary muscle dysfunction following acute myocardial infarction, operated on successfully].

PubMed

de Lima, R; Perdigão, C; Neves, L; Cravino, J; Dantas, M; Bordalo, A; Pais, F; Diogo, A N; Ferreira, R; Ribeiro, C

1990-09-01

The authors present a case of left ventricular free wall rupture post acute myocardial infarction, associated with mitral papillary posterior muscle necrosis, operated by infartectomy and mitral valvular protesis replacement. They refer the various complications occurred during the hospital staying, and discuss its medical and surgical approach. The patient was discharged alive and six months after the infarction keeps a moderate activity.

The relationship between ischemia-induced left ventricular dysfunction, coronary flow reserve, and coronary steal on regadenoson stress-gated (82)Rb PET myocardial perfusion imaging.

PubMed

Van Tosh, Andrew; Votaw, John R; Reichek, Nathaniel; Palestro, Christopher J; Nichols, Kenneth J

2013-12-01

Gated rubidium-82 ((82)Rb) positron emission tomography (PET) imaging studies are acquired both at rest and during pharmacologic stress. Stress-induced ischemic left ventricular dysfunction (LVD) can produce a significant decrease in left ventricular ejection fraction (LVEF) from rest to stress. We determined the prevalence on PET of stress LVD with reduced ejection fraction (EF) and its association with absolute global and regional coronary flow reserve (CFR), and with relative perfusion defect summed difference score (SDS). We studied 205 patients with known or suspected coronary disease (120 M, 75 F, age 69 ± 13 years) who had clinically indicated rest/regadenoson stress (82)Rb PET/CT studies. Data were acquired in dynamic gated list mode. Global and 17-segment regional CFR values were computed from first-pass flow data using a 2-compartment model and factor analysis applied to auto-generated time-activity curves. Rest and stress LVEF and SDS were quantified from gated equilibrium myocardial perfusion tomograms using Emory Cardiac Toolbox software. LVD was defined as a change in LVEF of ≤-5% from rest to stress. A subgroup of 109 patients also had coronary angiography. Stress LVD developed in 32 patients (16%), with mean EF change of -10 ± 5%, vs +6 ± 7% for patients without LVD (P < .0001). EF was similar at rest in patients with and without stress LVD (57 ± 18% vs 56 ± 16%, P = .63), but lower during stress for patients with LVD (47 ± 20% vs 61 ± 16%, P = .0001). CFR was significantly lower in patients with LVD (1.61 ± 0.67 vs 2.21 ± 1.03, Wilcoxon P = .002), and correlated significantly with change in EF (r = 0.35, P < .0001), but not with SDS (r = -0.13, P = .07). The single variable most strongly associated with high risk of CAD (i.e., left main stenosis ≥50%, LAD % stenosis ≥70%, and/or 3-vessel disease) was stress EF (χ(2) = 17.3, P < .0001). There was a higher prevalence of patients with

A functional genetic variant (N521D) in natriuretic peptide receptor 3 is associated with diastolic dysfunction: the prevalence of asymptomatic ventricular dysfunction study.

PubMed

Pereira, Naveen L; Redfield, Margaret M; Scott, Christopher; Tosakulwong, Nirubol; Olson, Timothy M; Bailey, Kent R; Rodeheffer, Richard J; Burnett, John C

2014-01-01

To evaluate the impact of a functional genetic variant in the natriuretic peptide clearance receptor, NPR3, on circulating natriuretic peptides (NPs) and myocardial structure and function in the general community. NPR3 plays an important role in the clearance of NPs and through direct signaling mechanisms modulates smooth muscle cell function and cardiac fibroblast proliferation. A NPR3 nonsynonymous single nucleotide polymorphism (SNP) rs2270915, resulting in a N521D substitution in the intracellular catalytic domain that interacts with Gi could affect receptor function. Whether this SNP is associated with alterations in NPs levels and altered cardiac structure and function is unknown. DNA samples of 1931 randomly selected residents of Olmsted County, Minnesota were genotyped. Plasma NT-proANP1-98, ANP1-28, proBNP1-108, NT-proBNP1-76, BNP1-32 and BNP3-32 levels were measured. All subjects underwent comprehensive echocardiography. Genotype frequencies for rs2270915 were as follows: (A/A 60%, A/G 36%, G/G 4%). All analyses performed were for homozygotes G/G versus wild type A/A plus the heterozygotes A/G. Diastolic dysfunction was significantly more common (p = 0.007) in the homozygotes G/G (43%) than the A/A+A/G (28%) group. Multivariate regression adjusted for age, sex, body mass index and hypertension demonstrated rs2270915 to be independently associated with diastolic dysfunction (odds ratio 1.94, p = 0.03). There was no significant difference in NPs levels between the 2 groups suggesting that the clearance function of the receptor was not affected. A nonsynonymous NPR3 SNP is independently associated with diastolic dysfunction and this association does not appear to be related to alterations in circulating levels of natriuretic peptides.

Phloretin ameliorates 2-chlorohexadecanal-mediated brain microvascular endothelial cell dysfunction in vitro.

PubMed

Ullen, Andreas; Fauler, Günter; Bernhart, Eva; Nusshold, Christoph; Reicher, Helga; Leis, Hans-Jörg; Malle, Ernst; Sattler, Wolfgang

2012-11-01

2-Chlorohexadecanal (2-ClHDA), a chlorinated fatty aldehyde, is formed via attack on ether-phospholipids by hypochlorous acid (HOCl) that is generated by the myeloperoxidase-hydrogen peroxide-chloride system of activated leukocytes. 2-ClHDA levels are elevated in atherosclerotic lesions, myocardial infarction, and neuroinflammation. Neuroinflammatory conditions are accompanied by accumulation of neutrophils (an ample source of myeloperoxidase) in the brain. Microvessel damage by inflammatory mediators and/or reactive oxidants can induce blood-brain barrier (BBB) dysfunction, a pathological condition leading to cerebral edema, brain hemorrhage, and neuronal death. In this in vitro study we investigated the impact of 2-ClHDA on brain microvascular endothelial cells (BMVEC), which constitute the morphological basis of the BBB. We show that exogenously added 2-ClHDA is subject to rapid uptake and metabolism by BMVEC. Using C16 structural analogues of 2-ClHDA we found that the cytotoxic potential decreases in the following order: 2-ClHDA>hexadecanal>palmitic acid>2-ClHDA-dimethylacetal. 2-ClHDA induces loss of barrier function, mitochondrial dysfunction, apoptosis via activation of caspase 3, and altered intracellular redox balance. Finally we investigated potential protective effects of several natural polyphenols on in vitro BBB function. Of the compounds tested, phloretin almost completely abrogated 2-ClHDA-induced BMVEC barrier dysfunction and cell death. These data suggest that 2-ClHDA has the potential to induce BBB breakdown under inflammatory conditions and that phloretin confers protection in this experimental setting. Copyright © 2012 Elsevier Inc. All rights reserved.

Acute myocardial infarction with changing axis deviation.

PubMed

Patanè, Salvatore; Marte, Filippo

2011-07-01

Changing axis deviation has been rarely reported also during atrial fibrillation or atrial flutter. Changing axis deviation has been rarely reported also during acute myocardial infarction associated with atrial fibrillation. Isolated left posterior hemiblock is a very rare finding but the evidence of transient right axis deviation with a left posterior hemiblock pattern has been reported during acute anterior myocardial infarction as related with significant right coronary artery obstruction and collateral circulation between the left coronary system and the posterior descending artery. Left anterior hemiblock development during acute inferior myocardial infarction can be an indicator of left anterior descending coronary artery lesions, multivessel coronary artery disease, and impaired left ventricular systolic function. We present a case of changing axis deviation in a 62-year-old Italian man with acute myocardial infarction. Also this case focuses attention on changing axis deviation during acute myocardial infarction. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Ameliorating Endothelial Mitochondrial Dysfunction Restores Coronary Function via Transient Receptor Potential Vanilloid 1-Mediated Protein Kinase A/Uncoupling Protein 2 Pathway.

PubMed

Xiong, Shiqiang; Wang, Peijian; Ma, Liqun; Gao, Peng; Gong, Liuping; Li, Li; Li, Qiang; Sun, Fang; Zhou, Xunmei; He, Hongbo; Chen, Jing; Yan, Zhencheng; Liu, Daoyan; Zhu, Zhiming

2016-02-01

Coronary heart disease arising from atherosclerosis is a leading cause of cardiogenic death worldwide. Mitochondria are the principal source of reactive oxygen species (ROS), and defective oxidative phosphorylation by the mitochondrial respiratory chain contributes to ROS generation. Uncoupling protein 2 (UCP2), an adaptive antioxidant defense factor, protects against mitochondrial ROS-induced endothelial dysfunction in atherosclerosis. The activation of transient receptor potential vanilloid 1 (TRPV1) attenuates vascular dysfunction. Therefore, whether TRPV1 activation antagonizes coronary lesions by alleviating endothelial mitochondrial dysfunction and enhancing the activity of the protein kinase A/UCP2 pathway warrants examination. ApoE(-/-), ApoE(-/-)/TRPV1(-/-), and ApoE(-/-)/UCP2(-/-) mice were fed standard chow, a high-fat diet (HFD), or the HFD plus 0.01% capsaicin. HFD intake profoundly impaired coronary vasodilatation and myocardial perfusion and shortened the survival duration of ApoE(-/-) mice. TRPV1 or UCP2 deficiency exacerbated HFD-induced coronary dysfunction and was associated with increased ROS generation and reduced nitric oxide production in the endothelium. The activation of TRPV1 by capsaicin upregulated UCP2 expression via protein kinase A phosphorylation, thereby alleviating endothelial mitochondrial dysfunction and inhibiting mitochondrial ROS generation. In vivo, dietary capsaicin supplementation enhanced coronary relaxation and prolonged the survival duration of HFD-fed ApoE(-/-) mice. These effects were not observed in ApoE(-/-) mice lacking the TRPV1 or UCP2 gene. The upregulation of protein kinase A /UCP2 via TRPV1 activation ameliorates coronary dysfunction and prolongs the lifespan of atherosclerotic mice by ameliorating endothelial mitochondrial dysfunction. Dietary capsaicin supplementation may represent a promising intervention for the primary prevention of coronary heart disease. © 2015 American Heart Association, Inc.

Stress Perfusion Cardiac Magnetic Resonance Imaging Effectively Risk Stratifies Diabetic Patients With Suspected Myocardial Ischemia.

PubMed

Heydari, Bobak; Juan, Yu-Hsiang; Liu, Hui; Abbasi, Siddique; Shah, Ravi; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y

2016-04-01

Diabetics remain at high risk of cardiovascular disease and mortality despite advancements in medical therapy. Noninvasive cardiac risk profiling is often more difficult in diabetics owing to the prevalence of silent ischemia with unrecognized myocardial infarction, reduced exercise capacity, nondiagnostic electrocardiographic changes, and balanced ischemia from diffuse epicardial coronary atherosclerosis and microvascular dysfunction. A consecutive cohort of 173 patients with diabetes mellitus (mean age, 61.7±11.9 years; 37% women) with suspected myocardial ischemia underwent stress perfusion cardiac magnetic resonance imaging. Patients were evaluated for adverse cardiac events after cardiac magnetic resonance imaging with mean follow-up time of 2.9±2.5 years. Mean hemoglobin A1c for the population was 7.9±1.8%. Primary end point was a composite of cardiac death and nonfatal myocardial infarction. Diabetics with no inducible ischemia (n=94) experienced an annualized event rate of 1.4% compared with 8.2% (P=0.0003) in those with inducible ischemia (n=79). Diabetics without late gadolinium enhancement or inducible ischemia had a low annual cardiac event rate (0.5% per year). The presence of inducible ischemia was the strongest unadjusted predictor (hazard ratio, 4.86; P<0.01) for cardiac death and nonfatal myocardial infarction. This association remained robust in adjusted stepwise multivariable Cox regression analysis (hazard ratio, 4.28; P=0.02). In addition, categorical net reclassification index using 5-year risk cutoffs of 5% and 10% resulted in reclassification of 43.4% of the diabetic cohort with net reclassification index of 0.38 (95% confidence interval, 0.20-0.56; P<0.0001). Stress perfusion cardiac magnetic resonance imaging provided independent prognostic utility and effectively reclassified risk in patients with diabetes mellitus referred for ischemic assessment. Further evaluation is required to determine whether a noninvasive imaging strategy with

Relation of cardiac troponin I and microvascular obstruction following ST-elevation myocardial infarction.

PubMed

Hallén, Jonas; Jensen, Jesper K; Buser, Peter; Jaffe, Allan S; Atar, Dan

2011-03-01

Presence of microvascular obstruction (MVO) following primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) confers higher risk of left-ventricular remodelling and dysfunction. Measurement of cardiac troponin I (cTnI) after STEMI reflects the extent of myocardial destruction. We aimed to explore whether cTnI values were associated with presence of MVO independently of infarct size in STEMI patients receiving pPCI. 175 patients with STEMI were included. cTnI was sampled at 24 and 48 h. MVO and infarct size was determined by delayed enhancement with cardiac magnetic resonance at five to seven days post index event. The presence of MVO following STEMI was associated with larger infarct size and higher values of cTnI at 24 and 48 h. For any given infarct size or cTnI value, there was a greater risk of MVO development in non-anterior infarctions. cTnI was strongly associated with MVO in both anterior and non-anterior infarctions (P < 0.01) after adjustment for covariates (including infarct size); and was reasonably effective in predicting MVO in individual patients (area-under-the-curve ≥0.81). Presence of MVO is reflected in levels of cTnI sampled at an early time-point following STEMI and this association persists after adjustment for infarct size.

Differences in autonomic nerve function in patients with silent and symptomatic myocardial ischaemia.

PubMed Central

Shakespeare, C. F.; Katritsis, D.; Crowther, A.; Cooper, I. C.; Coltart, J. D.; Webb-Peploe, M. W.

1994-01-01

BACKGROUND--Autonomic neuropathy provides a mechanism for the absence of symptoms in silent myocardial ischaemia, but characterisation of the type of neuropathy is lacking. AIM--To characterise and compare autonomic nerve function in patients with silent and symptomatic myocardial ischaemia. METHODS AND RESULTS--The Valsalva manoeuvre, heart rate variation (HRV) in response to deep breathing and standing, lower body negative pressure, isometric handgrip, and the cold pressor test were performed by patients with silent (n = 25) and symptomatic (n = 25) ambulatory ischaemia and by controls (n = 21). No difference in parasympathetic efferent function between patients with silent and symptomatic ischaemia was recorded, but both had significantly less HRV in response to standing than the controls (p < 0.005 for silent and p < 0.01 for symptomatic). Patients with silent ischaemia showed an increased propensity for peripheral vasodilatation compared with symptomatic patients (p < 0.02) and controls (p < 0.04). Impaired sympathetic function was found in patients with pure silent ischaemia (n = 4) compared with the remaining patients with silent ischaemia whose pain pathways were presumed to be intact. CONCLUSIONS--Patients with silent ischaemia and pain pathways presumed to be intact have an enhanced peripheral vasodilator response, and if this applied to the coronary vasculature it could provide a mechanism for limiting ischaemia to below the pain threshold. Patients with pure silent ischaemia have evidence of sympathetic autonomic dysfunction. Images PMID:8297687

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability.

PubMed

Lamers, F P L; van Dijkman, P R M; Kuijpers, Th J A; van Herpen, G

2003-02-01

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia. Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability. Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability

PubMed Central

Lamers, F.P.L.; van Dijkman, P.R.M.; Kuijpers, Th.J.A.; van Herpen, G.

2003-01-01

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia. Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability. Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was

An injectable silk sericin hydrogel promotes cardiac functional recovery after ischemic myocardial infarction.

PubMed

Song, Yu; Zhang, Cheng; Zhang, Jinxiang; Sun, Ning; Huang, Kun; Li, Huili; Wang, Zheng; Huang, Kai; Wang, Lin

2016-09-01

Acute myocardial infarction (MI) leads to morbidity and mortality due to cardiac dysfunction. Here we identify sericin, a silk-derived protein, as an injectable therapeutic biomaterial for the minimally invasive MI repair. For the first time, sericin prepared in the form of an injectable hydrogel has been utilized for cardiac tissue engineering and its therapeutical outcomes evaluated in a mouse MI model. The injection of this sericin hydrogel into MI area reduces scar formation and infarct size, increases wall thickness and neovascularization, and inhibits the MI-induced inflammatory responses and apoptosis, thereby leading to a significant functional improvement. The potential therapeutical mechanisms have been further analyzed in vitro. Our results indicate that sericin downregulates pro-inflammatory cytokines (TNF-α and IL-18) and chemokine (CCL2) and reduces TNF-α expression by suppressing the TLR4-MAPK/NF-κB pathways. Moreover, sericin exhibits angiogenic activity by promoting migration and tubular formation of human umbilical vessel endothelial cells (HUVECs). Also, sericin stimulates VEGFa expression via activating ERK phosphorylation. Further, sericin protects endothelial cells and cardiomyocytes from apoptosis by inhibiting the activation of caspase 3. Together, these diverse biochemical activities of sericin protein lead to a significant recovery of cardiac function. This work represents the first study reporting sericin as an effective therapeutic biomaterial for ischemic myocardial repair in vivo. Intramyocardial biomaterial injection is thought to be a potential therapeutic approach to improve cardiac performance after ischemic myocardial infarction. In this study, we report the successful fabrication and in vivo application of an injectable sericin hydrogel for ischemic heart disease. We for the first time show that the injection of in situ forming crosslinked sericin hydrogel promotes heart functional recovery accompanied with reduced

Transmyocardial laser revascularization in the acute ischaemic heart: no improvement of acute myocardial perfusion or prevention of myocardial infarction.

PubMed

Eckstein, F S; Scheule, A M; Vogel, U; Schmid, S T; Miller, S; Jurmann, M J; Ziemer, G

1999-05-01