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Sample records for acutely reperfused myocardial

  1. Acute oedema in the evaluation of microvascular reperfusion and myocardial salvage in reperfused myocardial infarction with cardiac magnetic resonance imaging.

    PubMed

    Phrommintikul, Arintaya; Abdel-Aty, Hassan; Schulz-Menger, Jeanette; Friedrich, Matthias G; Taylor, Andrew J

    2010-06-01

    The accurate measurement of myocardial salvage is critical to the ongoing refinement of reperfusion strategies in acute myocardial infarction (AMI). Cardiac magnetic resonance imaging (CMR) can define the area at risk in AMI by the presence of myocardial oedema, identified by high signal intensity on T(2)-weighted imaging with a short inversion time inversion-recovery (STIR) sequence. In addition, myocardial necrosis can be identified with CMR delayed contrast enhanced imaging. In this prospective study we examined the relationship of acute oedema and necrosis with impaired microvascular reperfusion. We also evaluated acute oedema as a marker of the area at risk in AMI, for the purposes of documenting myocardial salvage. CMR was performed on 15 patients with (AMI), within 24h of successful percutaneous coronary intervention (PCI). Left ventricular (LV) systolic dysfunction was defined by a systolic thickening <40% (severe <20%). Microvascular reperfusion was evaluated during the acute phase of contrast wash-in. CMR was repeated 3 months post-PCI to evaluate recovery of LV function and final infarct size. Myocardial salvage was defined as the percentage of the area at risk that was not infarcted on follow up CMR. There was a significant correlation between impaired microvascular reperfusion and the extent of segmental oedema (R=0.363, P<0.01), but not myocardial necrosis (R=0.110, P>0.5). The extent of myocardial salvage correlated with recovery of systolic function (R=0.241, P<0.05), which was strongest in LV segments with severely reduced systolic function (R=0.422, P<0.01). In acutely reperfused AMI, oedema can be used to identify the area at risk for the purpose of calculating myocardial salvage. The correlation between myocardial oedema and reperfusion status suggests a pathological role of acute oedema in the impairment of microvascular reperfusion. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  2. Acute effects of delayed reperfusion following myocardial infarction: a 3D x-ray imaging analysis

    NASA Astrophysics Data System (ADS)

    Simari, Robert D.; Bell, M. R.; Pao, Y. C.; Gersh, B. J.; Ritman, Erik L.

    1996-04-01

    Clinical and experimental data suggest that delayed reperfusion of the infarct related artery may limit infarct expansion without increasing myocardial salvage. In order to assess the potential mechanisms involved, an acute closed chest canine model of myocardial infarction and delayed reperfusion was studied. Nineteen dogs underwent 3D computed tomography in the Dynamic Spatial Reconstructor (a fast, volume imaging, CT scanner) at baseline and three and four hours later to estimate left ventricular chamber volumes, global distensibility and regional myocardial stiffness. A control group was scanned without intervention. An occlusion group underwent four hours of coronary artery occlusion. A reperfusion group underwent three hours of coronary artery occlusion followed by one hour of reperfusion. Similar infarct sizes were seen in the occlusion and reperfusion groups. Globally reperfusion was associated with increased left ventricular end diastolic pressure and prolongation of global relaxation. Regionally reperfusion was associated with increased myocardial stiffness, intramyocardial blood volume and wall thickness within the infarct zone relative to the not reperfused myocardium.

  3. Myocardium and microvessel endothelium apoptosis at day 7 following reperfused acute myocardial infarction.

    PubMed

    Kang, Sheng; Yang, Yue-jin; Wu, Yi-ling; Chen, Yu-tong; Li, Li; Tian, Yi

    2010-01-01

    This study was to investigate the salvaged myocardial and microvascular endothelial cells apoptosis at the first week of reperfused acute myocardial infarction (AMI). Sixteen mini swines (20-30 kg) were randomly assigned to the sham-operated group and the AMI group. The acute myocardial infarction and reperfusion model was created, and pathologic myocardial tissue was collected at day 7 following left anterior descending coronary artery reperfusion, and detected by transmission electron microscope, in situ cell apoptosis detection (TUNEL method), Real-time Quantitative Polymerase Chain Reaction and Western blot. In the AMI group, the infarcted area showed the myolysis, fibroblast and injuried endothelial cells under transmission electron microscope. The infarcted area had higher apoptotic index of microvascular endothelial cells than the marginal area, the normal area, and the sham-operated area (all P<0.05). Fas and Bax mRNA expressions in the infarcted area were higher than those in the marginal area, the normal area, and the sham-operated area (all P<0.05), and both protein overexpressions and Bcl-2 low expression in the infarcted and marginal areas compared with the normal area and the sham-operated area. The overexpressions of Fas and Bax or the low expression of Bcl-2 in the infarcted and marginal heart tissue may play an important role in the acceleration of myocardial and endothelial apoptosis at 7th day following reperfused acute myocardial infarction. Copyright 2009 Elsevier Inc. All rights reserved.

  4. Combined assessment of reflow and collateral blood flow by myocardial contrast echocardiography after acute reperfused myocardial infarction

    PubMed Central

    Leclercq, F; Messner-Pellenc, P; Descours, Q; Daures, J; Pasquie, J; Hager, F; Davy, J; Grolleau-Raoux, R

    1999-01-01

    OBJECTIVE—To evaluate the combined assessment of reflow and collateral blood flow by myocardial contrast echocardiography after myocardial infarction.
DESIGN—Myocardial contrast echocardiography was performed in patients with acute myocardial infarction shortly after successful coronary reperfusion (TIMI 3 patency) by direct angioplasty. Collateral flow was assessed before coronary angioplasty, and contrast reflow was evaluated 15 minutes after reperfusion. The presence of contractile reserve was assessed by low dose dobutamine echocardiography (5 to 15 µg/kg/min) at (mean (SD)) 3 (2) days after myocardial infarction. Recovery of segmental function (myocardial viability) was evaluated by resting echocardiography at a two month follow up. The study was prospective.
PATIENTS—35 consecutive patients referred for acute transmural myocardial infarction.
RESULTS—Contrast reflow was observed in 20 patients (57%) and collateral flow in 14 (40%). Contrast reflow and collateral contrast flow were both correlated with reversible dysfunction on initial dobutamine echocardiography and at follow up (p < 0.05). The presence of reflow or collateral flow on myocardial contrast echocardiography was a highly sensitive (100%) but weakly specific (60%) indicator of segmental dysfunction recovery. Simultaneous presence of contrast reflow and collateral flow was more specific of reversible dysfunction than reflow alone (90% v 60%).
CONCLUSIONS—Combined assessment of reflow and collateral blood flow enhanced the sensitivity of myocardial contrast echocardiography in predicting myocardial viability after acute, reperfused myocardial infarction. The simultaneous presence of reflow and collateral blood flow was highly specific of recovery of segmental dysfunction.


Keywords: contrast echocardiography; coronary reflow; collateral blood flow; dobutamine echocardiography; myocardial dysfunction PMID:10377311

  5. Ischemia/Reperfusion Injury following Acute Myocardial Infarction: A Critical Issue for Clinicians and Forensic Pathologists

    PubMed Central

    Neri, Margherita; Pascale, Natascha; Pomara, Cristoforo

    2017-01-01

    Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality. Reperfusion strategies are the current standard therapy for AMI. However, they may result in paradoxical cardiomyocyte dysfunction, known as ischemic reperfusion injury (IRI). Different forms of IRI are recognized, of which only the first two are reversible: reperfusion-induced arrhythmias, myocardial stunning, microvascular obstruction, and lethal myocardial reperfusion injury. Sudden death is the most common pattern for ischemia-induced lethal ventricular arrhythmias during AMI. The exact mechanisms of IRI are not fully known. Molecular, cellular, and tissue alterations such as cell death, inflammation, neurohumoral activation, and oxidative stress are considered to be of paramount importance in IRI. However, comprehension of the exact pathophysiological mechanisms remains a challenge for clinicians. Furthermore, myocardial IRI is a critical issue also for forensic pathologists since sudden death may occur despite timely reperfusion following AMI, that is one of the most frequently litigated areas of cardiology practice. In this paper we explore the literature regarding the pathophysiology of myocardial IRI, focusing on the possible role of the calpain system, oxidative-nitrosative stress, and matrix metalloproteinases and aiming to foster knowledge of IRI pathophysiology also in terms of medicolegal understanding of sudden deaths following AMI. PMID:28286377

  6. Serial transthoracic coronary Doppler shows complete reversibility of microvascular obstruction pattern at one month after reperfused acute myocardial infarction.

    PubMed

    Ober, Camelia Diana; Ober, Mihai Claudiu; Iancu, Adrian Corneliu

    2017-01-31

    "No reflow" phenomenon is a common complication with significant prognostic repercussions after reperfused acute myocardial infarction. Previous studies have shown the feasibility and prognostic significance of coronary microcirculation assessment by transthoracic Doppler of left anterior descending artery (LAD). The aim of the study was to evaluate the time course of the coronary microcirculation status after acute anterior myocardial infarction reperfused by primary angioplasty with stent on LAD.

  7. Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs.

    PubMed

    Kamat, Pranitha; Vandenberghe, Stijn; Christen, Stephan; Bongoni, Anjan K; Meier, Bernhard; Rieben, Robert; Khattab, Ahmed A

    2016-01-01

    Calcium and iron overload participate in the mechanisms of ischemia/reperfusion (I/R) injury during myocardial infarction (MI). Calcium overload induces cardiomyocyte death by hypercontraction, while iron catalyses generation of reactive oxygen species (ROS). We therefore hypothesized that dexrazoxane, an intracellular metal chelator, would attenuate I/R injury. MI was induced in pigs by occlusion of the left anterior descending artery for 1 hour followed by 2 hours reperfusion. Thirty minutes before reperfusion either 5 mg/ml dexrazoxane (n = 5) or saline (n = 5) was infused intravenously. Myocardial necrosis as percentage of the area at ischemic risk was found to be similar in both groups (77.2 ± 18% for dexrazoxane and 76.4 ± 14% for saline group) as determined by triphenyl tetrazolium chloride staining of the ischemic myocardium. Also, serum levels of troponin-I were similar in both groups. A conductance catheter was used to measure left ventricular pressure and volume at all times. Markers for tissue damage due to ROS (HNE), endothelial cell activation (CD31) and inflammation (IgG, C3b/c, C5b9, MCP-1) were assessed on tissue and/or in serum. No significant differences were observed between the groups for the parameters analyzed. To conclude, in this clinically relevant model of early reperfusion after acute myocardial ischemia, dexrazoxane lacked attenuating effects on I/R injury as shown by the measured parameters.

  8. Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs

    PubMed Central

    Kamat, Pranitha; Vandenberghe, Stijn; Christen, Stephan; Bongoni, Anjan K.; Meier, Bernhard; Rieben, Robert; Khattab, Ahmed A.

    2016-01-01

    Calcium and iron overload participate in the mechanisms of ischemia/reperfusion (I/R) injury during myocardial infarction (MI). Calcium overload induces cardiomyocyte death by hypercontraction, while iron catalyses generation of reactive oxygen species (ROS). We therefore hypothesized that dexrazoxane, an intracellular metal chelator, would attenuate I/R injury. MI was induced in pigs by occlusion of the left anterior descending artery for 1 hour followed by 2 hours reperfusion. Thirty minutes before reperfusion either 5 mg/ml dexrazoxane (n = 5) or saline (n = 5) was infused intravenously. Myocardial necrosis as percentage of the area at ischemic risk was found to be similar in both groups (77.2 ± 18% for dexrazoxane and 76.4 ± 14% for saline group) as determined by triphenyl tetrazolium chloride staining of the ischemic myocardium. Also, serum levels of troponin-I were similar in both groups. A conductance catheter was used to measure left ventricular pressure and volume at all times. Markers for tissue damage due to ROS (HNE), endothelial cell activation (CD31) and inflammation (IgG, C3b/c, C5b9, MCP-1) were assessed on tissue and/or in serum. No significant differences were observed between the groups for the parameters analyzed. To conclude, in this clinically relevant model of early reperfusion after acute myocardial ischemia, dexrazoxane lacked attenuating effects on I/R injury as shown by the measured parameters. PMID:28002439

  9. Conditioned blood reperfusion during angioplasty (CoBRA) treatment of acute myocardial infarction.

    PubMed

    Patel, M B; Kilgore, K S; Ortolano, G A; Gryboski, C L; Qureshi, M A; Marcovitz, P; Naylor, K B; Park, J L; Wenz, B; Gikakis, N; Freedman, R J; Lucchesi, B R; O'Neill, W W

    2001-03-01

    Acute myocardial infarct (MI) results in ischemia distal to lesions which puts heart muscle at risk for reperfusion injury (RI). Neutrophils, platelets and complement are putative mediators of RI. Recent advances in filtration technology provide integrated neutrophil and platelet removal together with complement-attenuating properties in a single blood-conditioning device. The present study characterizes the properties of a blood-conditioning filter and describes its clinical effect when used in conjunction with active hemoperfusion for acute MI. The filter reduces leukocytes by 99.9998 +/- 0.0002% (p<0.0001) and platelets by 99.9934 +/- 0.0069% (p<0.0001). Human plasma, derived from heparinized blood that was 'conditioned' by filtration, was studied using the Langendorff isolated rabbit heart preparation. The deposition of membrane attack complex and the resultant functional myocardial impairments [reflected in hemodynamic and biochemical measurements, including developed pressure, coronary blood flow, lymph-derived myocardial creatine kinase (CK)] are significantly attenuated by blood conditioning. Integration of the blood-conditioning filter into an active hemoperfusion system during primary percutaneous transluminal coronary angioplasty (PTCA) for acute MI (n=8) did not delay the procedure or cause any complications. Reperfusion of occluded coronary arteries with 300 cm3 of conditioned blood led to significant improvement in echocardiographic global wall motion scores (in standard deviations) following treatment (-1.64 +/- 0.18 to -1.45 +/- 0.15, p=0.02). Initial reperfusion of totally occluded coronary arteries with conditioned blood leads to acutely improved ventricular function. Collectively, these data provide a strong indication for continued investigation of conditioned blood reperfusion in angioplasty following acute MI for the long-term effect upon recovery of salvagable myocardium.

  10. Different contribution of extent of myocardial injury to left ventricular systolic and diastolic function in early reperfused acute myocardial infarction

    PubMed Central

    2014-01-01

    Background We sought to investigate the influence of the extent of myocardial injury on left ventricular (LV) systolic and diastolic function in patients after reperfused acute myocardial infarction (AMI). Methods Thirty-eight reperfused AMI patients underwent cardiac magnetic resonance (CMR) imaging after percutaneous coronary revascularization. The extent of myocardial edema and scarring were assessed by T2 weighted imaging and late gadolinium enhancement (LGE) imaging, respectively. Within a day of CMR, echocardiography was done. Using 2D speckle tracking analysis, LV longitudinal, circumferential strain, and twist were measured. Results Extent of LGE were significantly correlated with LV systolic functional indices such as ejection fraction (r = -0.57, p < 0.001), regional wall motion score index (r = 0.52, p = 0.001), and global longitudinal strain (r = 0.56, p < 0.001). The diastolic functional indices significantly correlated with age (r = -0.64, p < 0.001), LV twist (r = -0.39, p = 0.02), average non-infarcted myocardial circumferential strain (r = -0.52, p = 0.001), and LV end-diastolic wall stress index (r = -0.47, p = 0.003 with e’) but not or weakly with extent of LGE. In multivariate analysis, age and non-infarcted myocardial circumferential strain independently correlated with diastolic functional indices rather than extent of injury. Conclusions In patients with timely reperfused AMI, not only extent of myocardial injury but also age and non-infarcted myocardial function were more significantly related to LV chamber diastolic function. PMID:24512272

  11. Tramadol alleviates myocardial injury induced by acute hindlimb ischemia reperfusion in rats.

    PubMed

    Takhtfooladi, Hamed Ashrafzadeh; Asl, Adel Haghighi Khiabanian; Shahzamani, Mehran; Takhtfooladi, Mohammad Ashrafzadeh; Allahverdi, Amin; Khansari, Mohammadreza

    2015-08-01

    Organ injury occurs not only during periods of ischemia but also during reperfusion. It is known that ischemia reperfusion (IR) causes both remote organ and local injuries. This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR. Thirty healthy mature male Wistar rats were allocated randomly into three groups: Group I (sham), Group II (IR), and Group III (IR + tramadol). Ischemia was induced in anesthetized rats by left femoral artery clamping for 3 h, followed by 3 h of reperfusion. Tramadol (20 mg/kg, intravenous) was administered immediately prior to reperfusion. At the end of the reperfusion, animals were euthanized, and hearts were harvested for histological and biochemical examination. The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were higher in Groups I and III than those in Group II (p < 0.05). In comparison with other groups, tissue malondialdehyde (MDA) levels in Group II were significantly increased (p < 0.05), and this increase was prevented by tramadol. Histopathological changes, including microscopic bleeding, edema, neutrophil infiltration, and necrosis, were scored. The total injuryscore in Group III was significantly decreased (p < 0.05) compared with Group II. From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model.

  12. Garlicin attenuates reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction.

    PubMed

    Peng, Yang; Jiahui, Li; Aili, Li; Yong, Wang; Zaixiang, Shi; Yuannan, Ke; Xianlun, Li

    2012-08-01

    To evaluate whether garlicin can attenuate reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). Twenty-two swine were used: six in a sham-operation group, and eight each in the control and garlicin groups. The distal part of the left anterior descending coronary artery (LAD) in the latter two groups was occluded by a dilated balloon for 2 hr, then reperfused for 3 hr. Garlicin (1.88mg/kg) was injected just before reperfusion until reperfusion for 1 hr in the garlicin group. Hemodynamic data were examined before AMI, 2 hr after occlusion, and 3 hr after reperfusion. Myocardial contrast echocardiography (MCE) and pathological staining were performed to evaluate the myocardial no-reflow area (NRA). Serum proinflammatory cytokines and endothelin (ET)-1 were examined by radioimmunoassay. Left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) significantly improved in the garlicin group after reperfusion compared with the control group and also 2hr after AMI (p<0.05 for both). MCE and pathological staining both showed garlicin attenuated reperfusion NRA after AMI (p<0.05, p<0.01). Garlicin not only decreased serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α after reperfusion (p<0.05 for both), but also ET-1 level (p<0.01). Garlicin attenuated reperfusion no-reflow in our catheter-based porcrine model of AMI, possibly through decreasing serum proinflammatory cytokines and ET-1.

  13. Detection and evaluation of renal biomarkers in a swine model of acute myocardial infarction and reperfusion.

    PubMed

    Duan, Su-Yan; Xing, Chang-Ying; Zhang, Bo; Chen, Yan

    2015-01-01

    The prevalence of type 1 cardiorenal syndrome (CRS) is increasing and strongly associated with long-term mortality. However, lack of reliable animal models and well-defined measures of renoprotection, made early diagnosis and therapy difficult. We previously successfully established the swine acute myocardial infarction (AMI) model of ischemia-reperfusion by blocking left anterior descending branch (LAD). Reperfusion was performed after 90-minute occlusion of the LAD. AMI was confirmed by ECG and left ventricular angiography (LVG). Then those 52 survived AMI reperfusion swine, including ventricular fibrillation-cardiac arrest after restoration of blood flow, were randomly divided into four groups (four/group) according to different interventions: resuscitation in room temperature, resuscitation with 500 ml saline in room temperature, resuscitation with 4°C 500 ml saline and normal control (with no intervention of resuscitation). Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias: 1, 3, 5, 10-minute reperfusion after ventricular arrhythmias. Plasma and random urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury (AKI). Our swine AMI model of ischemia-reperfusion provoked subclinical AKI with the elevation of the tubular damage biomarker, NGAL, IL-18 and L-FABP. Renal damage rapidly observed after hemodynamic instability, rather than observation after several hours as previously reported. The increasing rate of biological markers declined after interventions, however, its impact on the long-term prognosis remains to be further studied. These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS.

  14. New perspectives on the role of cardiac magnetic resonance imaging to evaluate myocardial salvage and myocardial hemorrhage after acute reperfused ST-elevation myocardial infarction.

    PubMed

    Mangion, Kenneth; Corcoran, David; Carrick, David; Berry, Colin

    2016-07-01

    Cardiac magnetic resonance (CMR) imaging enables the assessment of left ventricular function and pathology. In addition to established contrast-enhanced methods for the assessment of infarct size and microvascular obstruction, other infarct pathologies, such as myocardial edema and myocardial hemorrhage, can be identified using innovative CMR techniques. The initial extent of myocardial edema revealed by T2-weighted CMR has to be stable for edema to be taken as a retrospective marker of the area-at-risk, which is used to calculate myocardial salvage. The timing of edema assessment is important and should be focused within 2 - 7 days post-reperfusion. Some recent investigations have called into question the diagnostic validity of edema imaging after acute STEMI. Considering the results of these studies, as well as results from our own laboratory, we conclude that the time-course of edema post-STEMI is unimodal, not bimodal. Myocardial hemorrhage is the final consequence of severe vascular injury and a progressive and prognostically important complication early post-MI. Myocardial hemorrhage is a therapeutic target to limit reperfusion injury and infarct size post-STEMI.

  15. [Reperfusion and postconditioning in acute ST segment elevation myocardial infarction. A new paradigm for the treatment of acute myocardial infarction. From bench to bedside?].

    PubMed

    Lupi Herrera, Eulo; Gaspar, Jorge; González Pacheco, Héctor; Martínez Sánchez, Carlos; Pastelín Hernández, Gustavo; Luna Ortiz, Pastor; Chávez Cosio, Edmundo

    2006-01-01

    After prolonged periods of ischemia and energy depletion, the ischemic myocardial cell can be jeopardized by specific causes within the reperfusion period. These causes can be viewed as unwanted aspects of the recovery process itself limiting its efficiency. Three potential initial causes of immediate reperfusion injury, aside from oxygen radicals, have been experimentally investigated in detail, and are briefly discussed: 1. re-energization; 2. rapid normalization of tissue pH; and 3. rapid normalization of tissue osmolality. These potential causes are not entirely independent. Understanding of the basic causes has opened novel perspectives for specific interference with these serious pathomechanisms. The experimental results obtained in the last years encourage the development of therapeutic approaches to reduce infarct size by specific measures applied during the early phase of reperfusion. In the clinical setting, reperfusion therapy for acute myocardial infarction (AMI) has shown to reduce mortality, yet it may also have deleterious effects, including myocardial necrosis and no-reflow. Almost two decades ago, great hope arose from the description of ischemic preconditioning. Unfortunately, ischemic preconditioning is not feasible in the clinical practice because the coronary artery is already occluded at the time of hospital admission of the AMI patient. Recently, in the dog model, a phenomenon called "postconditioning" has been described. It has been reported previouly that reperfusion injury can be significantly reduced by modifying the conditions and the composition of the initial reperfusate. Whereas preconditioning is triggered by brief episodes of ischemia-reperfusion performed just before a prolonged coronary artery occlusion, postconditioning is induced by a comparable sequence of reversible ischemia-reperfusion, but it is applied "just after the prolonged" ischemic insult. Protection afforded by postconditioning is as potent as that provided by

  16. Comparison of five cardiac markers in the detection of reperfusion after thrombolysis in acute myocardial infarction.

    PubMed Central

    Lavin, F.; Kane, M.; Forde, A.; Gannon, F.; Daly, K.

    1995-01-01

    OBJECTIVE--To investigate and compare the clinical usefulness of serial measurements of five cardiac marker proteins, namely creatine kinase (CK), CK-MB mass, myoglobin, troponin T, and myosin light chain 1, in the early detection of reperfusion after thrombolytic treatment. METHOD--Serial blood samples were taken from 26 patients presenting with acute myocardial infarction. Concentrations of the five markers were assayed in each sample. Thrombolytic treatment was given to the patients who were divided into those who reperfused (n = 17, group A) and those who failed to reperfuse (n = 9, group B) on the basis of clinical signs and angiography within 24 h. RESULTS--The release profiles of CK, CK-MB mass, myoglobin, and troponin T for patients in group A differed from those of patients in group B. No difference was observed in the release profile of myosin light chain 1 between the two groups. The time to peak concentration of CK, CK-MB mass, myoglobin, and troponin T occurred significantly earlier in patients of group A than in those of group B, with myoglobin peaking earlier than the other markers. An index, defined as the ratio of the concentration of each marker immediately before and 2 h after the start of thrombolytic treatment, was calculated for each marker in groups A and B. The 2 h myoglobin and troponin T indices were significantly different between groups A and B. The diagnostic efficiency of the myoglobin index, however, was best at 85%. CONCLUSIONS--These studies suggest that myoglobin has greater potential than the other markers examined in the detection of reperfusion after thrombolytic treatment. PMID:7786656

  17. Circadian variation in acute myocardial infarct size assessed by cardiovascular magnetic resonance in reperfused STEMI patients.

    PubMed

    Bulluck, Heerajnarain; Nicholas, Jennifer; Crimi, Gabriele; White, Steven K; Ludman, Andrew J; Pica, Silvia; Raineri, Claudia; Cabrera-Fuentes, Hector A; Yellon, Derek; Rodriguez-Palomares, Jose; Garcia-Dorado, David; Hausenloy, Derek J

    2017-03-01

    Clinical studies using serum cardiac biomarkers to investigate a circadian variation in acute myocardial infarct (MI) size in ST-segment elevation myocardial infarction (STEMI) patients reperfused by primary percutaneous coronary intervention (PPCI) have produced mixed results. We aimed to investigate this phenomenon using acute MI size measured by cardiovascular magnetic resonance (CMR). Patient-level data was obtained from 4 randomized controlled trials investigating the MI-limiting effects of cardioprotective therapies in this pooled analysis. The primary analysis was performed in those patients with no pre-infarct angina; duration of ischemia >60min and <360min; Thrombolysis In Myocardial Infarction (TIMI) flow pre-PPCI ≤1; TIMI flow post-PPCI 3; and no collateral flow. 169 out of 376 patients with CMR data met the inclusion criteria for the primary analysis. A 24-hour circadian variation in acute MI size as a % of the area-at-risk (%AAR), after adjusting for confounders, was observed with a peak and nadir MI size in patients with symptom onset between 00:00 and 01:00 and between 12:00 and 13:00 respectively (difference from the average MI size 5.2%, 95%CI 1.1-9.4%; p=0.013). This was associated with a non-significant circadian variation in left ventricular ejection fraction (LVEF) (difference from the average LVEF 5.9%, 95%CI -0.6-2.2%, p=0.073). There was no circadian variation in MI size or LVEF in the whole cohort. We report a circadian variation in acute MI size assessed by CMR in a subset of STEMI patients treated by PPCI, with the largest and smallest MI size occurring in patients with symptom onset between 00:00 and 01:00 and between 12:00 and 13:00 respectively. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Quantitative myocardial perfusion measurement using CT perfusion: a validation study in a porcine model of reperfused acute myocardial infarction.

    PubMed

    So, Aaron; Hsieh, Jiang; Li, Jian-Ying; Hadway, Jennifer; Kong, Hua-Fu; Lee, Ting-Yim

    2012-06-01

    We validated a CT perfusion technique with beam hardening (BH) correction for quantitative measurement of myocardial blood flow (MBF). Acute myocardial infarction (AMI) was created in four pigs by occluding the distal LAD for 1 h followed by reperfusion. MBF was measured from dynamic contrast enhanced CT (DCE-CT) scanning of the heart, with correction of cardiac motion and BH, before ischemic insult and on day 7, 10 and 14 post. On day 14 post, radiolabeled microspheres were injected to measure MBF and the results were compared with those measured by CT perfusion. Excised hearts were stained with 2,3,5-triphenyltetrazolium chloride (TTC) to determine the relationship between MBF measured by CT Perfusion and myocardial viability. MBF measured by CT perfusion was strongly correlated with that by microspheres over a wide range of MBF values (R = 0.81, from 25 to 225 ml min(-1) 100 g(-1)). While MBF in the LAD territory decreased significantly from 98.4 ± 2.5 ml min(-1) 100 g(-1) at baseline to 32.2 ± 9.1 ml min(-1) 100 g(-1), P < 0.05 at day 7 and to 49.4 ± 9.3 ml min(-1) 100 g(-1), P < 0.05 at day 14, the decrease in remote myocardium (LCx territory) from baseline (103.9 ± 1.9 ml min(-1) 100 g(-1)) was minimal throughout the study (90.6 ± 5.1 ml min(-1) 100 g(-1) on day 14 post, P > 0.05). TTC staining confirmed incomplete infarction in the LAD territory and no infarction in the LCx territory. Microvascular obstruction in infarcted tissue resulted in no-reflow and hence persistently low MBF in the reperfused LAD territory which contained a mixture of viable and non-viable tissue. CT perfusion measurement of MBF was accurate and correlated well with histology and microspheres measurements.

  19. Myocardial ischemia-reperfusion injury: a neglected therapeutic target

    PubMed Central

    Hausenloy, Derek J.; Yellon, Derek M.

    2013-01-01

    Acute myocardial infarction (MI) is a major cause of death and disability worldwide. In patients with MI, the treatment of choice for reducing acute myocardial ischemic injury and limiting MI size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention (PPCI). However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is still no effective therapy. A number of new therapeutic strategies currently under investigation for preventing myocardial reperfusion injury have the potential to improve clinical outcomes in patients with acute MI treated with PPCI. PMID:23281415

  20. Pharmacological prevention of reperfusion injury in acute myocardial infarction. A potential role for adenosine as a therapeutic agent.

    PubMed

    Quintana, Miguel; Kahan, Thomas; Hjemdahl, Paul

    2004-01-01

    The concept of reperfusion injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. Although the pathophysiology of reperfusion injury is complex, the major role that neutrophils play in this process is well known. Neutrophils generate free radicals, degranulation products, arachidonic acid metabolites and platelet-activating factors that interact with endothelial cells, inducing endothelial injury and neutralization of nitrous oxide vasodilator capacity. Adenosine, through its multi-targeted pharmacological actions, is able to inhibit some of the above-mentioned detrimental effects. The net protective of adenosine in in vivo models of reperfusion injury is the reduction of the infarct size, the improvement of the regional myocardial blood flow and of the regional function of the ischemic area. Additionally, adenosine preserves the post-ischemic coronary flow reserve, coronary blood flow and the post-ischemic regional contractility. In small-scale studies in patients with acute MI, treatment with adenosine has been associated with smaller infarcts, less no-reflow phenomenon and improved LV function. During elective PCI adenosine reduced ST segment shifts, lactate production and ischemic symptoms. During the

  1. Heart fatty acid binding protein and myoglobin after reperfusion of acute myocardial infarction.

    PubMed

    Ozdemir, Murat; Durakoğlugil, Emre; Gülbahar, Ozlem; Turkoglu, Sedat; Sancak, Banu; Paşaoğlu, Hatice; Cengel, Atiye

    2007-10-01

    The aim of this study was to disclose the release kinetics of heart fatty acid binding protein (HFABP) and myoglobin in acute myocardial infarction (AMI) reperfused by primary percutaneous coronary intervention (PPCI) and to determine the influence of the quality of coronary flow post PPCI on the release properties of these markers. Twenty-four patients with AMI who underwent successful PPCI and had no evidence of reocclusion within the first 120 minutes were studied. Serum myoglobin and HFABP levels at baseline and at 15, 30, 45, 60, 90 and 120 minutes after reperfusion were measured. Corrected TIMI frame count (CTFC) in the relevant vessel post PPCI was used to categorize patients in group I (CTFC > 21) and group 2 (CTFC < or = 21). Biomarker ratios at each sampling point were calculated by dividing the serum level of the biomarker at the specific sampling time by its baseline level. Baseline myoglobin and HFABP levels rose significantly at 15 minutes (153 +/- 251.5 microg/L vs. 904.3 +/- 542.6 microg/L, 10.9 +/- 8 microg/L vs. 17.8 +/- 9.1 microg/L, both P < 0.0001) after successful PPCI. Group 2 patients tended to have higher biomarker ratios at each time point as compared to group I. Successful PPCI for AMI results in a significant increase of both HFABP and myoglobin levels within 15 minutes of vessel opening and the quality of flow in the infarction-related artery post PCI as evaluated by CTFC does not influence the release kinetics of these biomarkers.

  2. Rheumatoid arthritis patients receive less frequent acute reperfusion and secondary prevention therapy after myocardial infarction compared with the general population

    PubMed Central

    2010-01-01

    Introduction The 30-day case-fatality rate after acute myocardial infarction (MI) for rheumatoid arthritis (RA) patients is twice that of the general population. This study compared the frequency and timeliness of early reperfusion therapy and treatment with secondary prevention medications after acute MI in RA patients and controls. Methods We performed a structured medical chart review of RA patients and matched controls who had been admitted with acute MI to one of three hospitals in Victoria, Australia, between 1995 and 2005. The administration and timing of acute reperfusion therapy and in-hospital treatment with secondary prevention medications were compared between the two groups. Acute reperfusion was defined as thrombolysis or percutaneous coronary intervention (PCI) within 12 hours of the first symptom of MI. Results The medical charts of 90 RA patients and 90 matched controls were reviewed. The RA patients were significantly less likely to receive acute reperfusion compared with the controls (16% versus 37%: odds ratio (OR), 0.27; 95% confidence interval (CI), 0.10 to 0.64)), and this difference persisted after adjusting for type of MI, clinical setting of MI, and prior MI (OR, 0.2; 95% CI, 0.05 to 0.6). The RA patients also received less-frequent in-hospital treatment with beta blockers (71% versus 83%; OR, 0.42; 95% CI, 0.18 to 0.96) and lipid-lowering agents (40% versus 70%; OR, 0.21; 95% CI, 0.09 to 0.46). Conclusions RA patients who experience acute MI receive acute reperfusion and secondary prevention medications less frequently than do controls. This may contribute to higher case-fatality rates after MI in RA patients. PMID:20929534

  3. Do antioxidant vitamins reduce infarct size following acute myocardial ischemia/reperfusion?

    PubMed

    Bellows, S D; Hale, S L; Simkhovich, B Z; Kay, G L; Kloner, R A

    1995-02-01

    There is controversy concerning the ability of antioxidant vitamins to reduce myocardial infarct size. We sought to determine whether a brief prophylactic treatment of vitamin C or vitamin C plus Trolox (a water-soluble form of vitamin E) could reduce myocardial infarct size in an experimental model. We used an anesthetized open-chest rabbit model in which a branch of the circumflex coronary artery was ligated for 30 minutes followed by 4 hours of reperfusion. Experiments were performed in a randomized and blinded fashion. An IV injection of normal saline pH balanced to 7.4 (control group n = 15), vitamin C (150 mg/kg, n = 14), or vitamin C plus Trolox (150 mg/kg plus 100 mg/kg, respectively, n = 15) was administered prior to coronary occlusion. Collateral blood flow during coronary occlusion was measured by radioactive microspheres, myocardial risk zone (AR) was assessed by blue dye injection, and myocardial infarct size (AN) was assessed by triphenyltetrazolium chloride staining. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar among all three groups. Infarct size, measured as a percent of AR, did not differ significantly among the controls (21%), vitamin C (29%), or the vitamin C plus Trolox (18%) groups. Therefore, in this ischemia/reperfusion model, antioxidant vitamins did not alter myocardial infarct size.

  4. Effect of streptokinase on reperfusion after acute myocardial infarction and its complications: an ex-post facto study.

    PubMed

    Taheri, Leila; Boroujeni, Ali Zargham; Kargar Jahromi, Marzieh; Charkhandaz, Maryam; Hojat, Mohsen

    2015-01-01

    Emergency treatment of patients with acute myocardial infarction is very important. Streptokinase in Iran is often as the only clot-busting medication is used. The purpose of using streptokinase medication is to revive the ischemic heart tissue, although has dangerous complications too. Therefore, the present study aimed to determine the effect of streptokinase on reperfusion after acute myocardial infarction and its complications, has been designed and conducted. This is an Ex-post facto study. The study population included patients who suffer from acute myocardial infarction. The sample size was 300 patients, and 2 groups were matched, in variables of age, sex, underlying disease, frequencies and area of MI. Data collection did by researcher making questionnaire, that accept face and content validity by 10 expert researcher, the reliability was conducted with Spearman's test (r=0.85) by Test-retest method. Data analysis did by SPSS software: V 12. Mean of EF in SK group was (46.15±8.11) and in control group was (43.11±12.57). Significant relationship was seen between SK, arrhythmia occurring and improve EF reperfusion by chi-square test (p=0.028), (p=0.020).The most arrhythmia in SK group was Ventricular Tachycardia (20.7%). Significant statistical relation between SK and mortality were found by Chi-square test (p=0.001). But a meaningful statistical relation was not found between SK and pulmonary edema incidence (p=0.071). Nurses of CCU should be aware about SK complications such as hypotension, bleeding and arrhythmias. Proposed compare SK and tissue plasminogen drug in reperfusion and complications effect.

  5. Effect of Streptokinase on Reperfusion After Acute Myocardial Infarction and Its Complications: An Ex-Post Facto Study

    PubMed Central

    Taheri, Leila; Zargham-Boroujeni, Ali; Jahromi, Marzieh Kargar; Charkhandaz, Maryam; Hojat, Mohsen

    2015-01-01

    Introduction: Emergency treatment of patients with acute myocardial infarction is very important. Streptokinase in Iran is often as the only clot-busting medication is used. The purpose of using streptokinase medication is to revive the ischemic heart tissue, although has dangerous complications too. Therefore, the present study aimed to determine the effect of streptokinase on reperfusion after acute myocardial infarction and its complications, has been designed and conducted. Materials and Methods: This is an Ex-post facto study. The study population included patients who suffer from acute myocardial infarction. The sample size was 300 patients, and 2 groups were matched, in variables of age, sex, underlying disease, frequencies and area of MI. Data collection did by researcher making questionnaire, that accept face and content validity by 10 expert researcher, the reliability was conducted with Spearman’s test (r=0.85) by Test-retest method. Data analysis did by SPSS software: V 12. Findings: Mean of EF in SK group was (46.15±8.11) and in control group was (43.11±12.57). Significant relationship was seen between SK, arrhythmia occurring and improve EF reperfusion by chi-square test (p=0.028), (p=0.020). The most arrhythmia in SK group was Ventricular Tachycardia (20.7%). Significant statistical relation between SK and mortality were found by Chi-square test (p=0.001). But a meaningful statistical relation was not found between SK and pulmonary edema incidence (p=0.071). Conclusions: Nurses of CCU should be aware about SK complications such as hypotension, bleeding and arrhythmias. Proposed compare SK and tissue plasminogen drug in reperfusion and complications effect. PMID:25946921

  6. Assessment of circumferential endocardial extent of myocardial edema and infarction in patients with reperfused acute myocardial infarction: a cardiovascular magnetic resonance study.

    PubMed

    Ota, Shingo; Tanimoto, Takashi; Hirata, Kumiko; Orii, Makoto; Shiono, Yasutsugu; Shimamura, Kunihiro; Ishibashi, Kohei; Yamano, Takashi; Ino, Yasushi; Kitabata, Hironori; Yamaguchi, Tomoyuki; Kubo, Takashi; Imanishi, Toshio; Akasaka, Takashi

    2014-01-01

    T2 weighted (T2W) images on cardiovascular magnetic resonance (CMR) visualizes myocardial edema, which reflects the myocardial area at risk (AAR) in reperfused acute myocardial infarction (AMI). Late gadolinium enhancement (LGE) demonstrates myocardial infarction. LGE images cover the whole left ventricle, but T2W images are obtained from a few slices of the left ventricle due to the long sequence time, so the quantification of AAR of the entire left ventricle is difficult. We hypothesize that we can quantify AAR with only LGE images if there is a strong correlation between the circumferential endocardial extent of myocardial edema and infarction. Thirty patients with first AMI were enrolled. All patients underwent successfully reperfusion therapy and CMR was performed within the first week after the event. We measured the circumferential extent of edema and infarction on short-axis views (T2 angle and LGE angle), respectively. A total of 82 short-axis slices showed transmural edema on T2W images. Corresponding LGE images were analyzed for the circumferential extent of infarction. The median [interquartile range] of T2 angle and DE angle were 147° [116°-219°] and 134° [104°-200°] in patients with LAD culprit lesion, 91° [87°-101°] and 85° [80°-90°] in LCX, and 110° [94°-123°] and 104° [89°-118°] in RCA, respectively. T2 angle was well correlated with LGE angle (r = 0.99, P < 0.01). There is a strong correlation between the circumferential extent of edema and infarction in reperfused AMI. Thus, T2 weighted imaging can be skipped to quantify the amount of AAR.

  7. Delay to reperfusion in patients with acute myocardial infarction presenting to acute care hospitals: an international perspective

    PubMed Central

    Spencer, Frederick A.; Montalescot, Gilles; Fox, Keith A.A.; Goodman, Shaun G.; Granger, Christopher B.; Goldberg, Robert J.; Oliveira, Gustavo B.F.; Anderson, Frederick A.; Eagle, Kim A.; Fitzgerald, Gordon; Gore, Joel M.

    2010-01-01

    Aims To examine the extent of delay from initial hospital presentation to fibrinolytic therapy or primary percutaneous coronary intervention (PCI), characteristics associated with prolonged delay, and changes in delay patterns over time in patients with ST-segment elevation myocardial infarction (STEMI). Methods and results We analysed data from 5170 patients with STEMI enrolled in the Global Registry of Acute Coronary Events from 2003 to 2007. The median elapsed time from first hospital presentation to initiation of fibrinolysis was 30 min (interquartile range 18–60) and to primary PCI was 86 min (interquartile range 53–135). Over the years under study, there were no significant changes in delay times to treatment with either strategy. Geographic region was the strongest predictor of delay to initiation of fibrinolysis >30 min. Patient's transfer status and geographic location were strongly associated with delay to primary PCI. Patients treated in Europe were least likely to experience delay to fibrinolysis or primary PCI. Conclusion These data suggest no improvements in delay times from hospital presentation to initiation of fibrinolysis or primary PCI during our study period. Geographic location and patient transfer were the strongest predictors of prolonged delay time, suggesting that improvements in modifiable healthcare system factors can shorten delay to reperfusion therapy even further. PMID:20231154

  8. Impact of reperfusion therapy and infarct localization on frequency of premature ventricular beats in acute myocardial infarction.

    PubMed

    Horvat, Davor; Vincelj, Josip

    2015-08-01

    To determine the impact of infarct localization and types of reperfusion therapy on the frequency of ventricular premature beats (VPBs) in patients with acute myocardial infarction (AMI) and reduced left ventricular ejection fraction (LVEF). A total of 705 patients with acute ST elevation myocardial infarction (STEMI) were divided according to the infarct localization (anteroseptal, anterolateral, inferior and posterior) and reperfusion therapy (fibrinolysis or percutaneous coronary intervention with stenting) into two groups: LVEF<45% was an experimental group and LVEF>45% was a control group. The occurrence of VPBs<10 per hour was defined as a non-significant, and the occurrence of VPBs>10 per hour defined as a significant. In patients with fibrinolysis therapy and LVEF<45% significant number of VPBs were in anteroseptal (p=0.017), anterolateral (p<0.001) and posterior AMI (p<0.001), but in patients with percutaneous coronary intervention (PCI) and LVEF<45% significant number of VPBs were only in anteroseptal AMI (p=0.001) localization. In patients with reduced ejection fraction in AMI, treatment with PCI method has a better antiarrhythmic effect compared to fibrinolysis treatment. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

  9. Both endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after acute ischemia and reperfusion.

    PubMed

    Wang, Meijing; Wang, Yue; Abarbanell, Aaron; Tan, Jiangjing; Weil, Brent; Herrmann, Jeremy; Meldrum, Daniel R

    2009-08-01

    Signal transducer and activator of transduction 3 (STAT3) pathway has been shown to be cardioprotective. We observed decreased STAT3/suppressor of cytokine signaling 3 (SOCS3) in male hearts, which was associated with worse postischemic myocardial function compared with females. However, it is unclear whether this downregulation of myocardial STAT3/SOCS3 is due to testosterone in males. We hypothesized that after ischemia/reperfusion (I/R), (1) endogenous testosterone decreases myocardial STAT3 and SOCS3 in males, and (2) administration of exogenous testosterone reduces myocardial STAT3/SOCS3 in female and castrated male hearts. To study this, hearts from I/R injury (Langendorff) were homogenized and assessed for phosphorylated-STAT3 (p-STAT3), total-STAT3 (T-STAT3), SOCS3, and GAPDH by Western blot. We grouped age-matched adult males, females, castrated males, males with androgen receptor blocker-flutamide implantation, females, and castrated males with chronic (3-week) 5alpha-dihydrotestosterone (DHT) release pellet implantation or acute (5-minute) testosterone infusion (ATI) before ischemia (n = 5-9 per group). Castration or flutamide treatment significantly increased SOCS3 expression in male hearts after I/R. However, only castration increased myocardial STAT3 activation. Notably, DHT replacement or ATI decreased markedly myocardial STAT3/SOCS3 in castrated males and females subjected to I/R. These results suggest that endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after I/R. This represents the initial demonstration of testosterone-downregulated STAT3/SOCS3 signaling in myocardium.

  10. Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction by Biomarkers

    ClinicalTrials.gov

    2017-03-02

    Acute Myocardial Infarction (AMI); Acute Coronary Syndrome (ACS); ST Elevation (STEMI) Myocardial Infarction; Ischemic Reperfusion Injury; Non-ST Elevation (NSTEMI) Myocardial Infarction; Angina, Unstable

  11. Usefulness of the presenting electrocardiogram in predicting successful reperfusion with streptokinase in acute myocardial infarction.

    PubMed

    Wong, C K; French, J K; Aylward, P E; Frey, M J; Adgey, A A; White, H D

    1999-01-15

    The presenting electrocardiogram may contain information indicating the probability of successful reperfusion. The relation between 3 parameters in the presenting electrocardiogram (pathologic Q waves, T-wave inversion, and the slope of ST elevation) and Thrombolysis in Myocardial Infarction trial (TIMI) grade 3 flow in the infarct-related artery was assessed angiographically 90 minutes after beginning streptokinase in 362 patients. TIMI grade 3 flow was more common in patients without Q waves (55%) than in those with Q waves (35%; p <0.001), and more common in patients without T-wave inversion (50%) than in those with T-wave inversion (30%; p <0.002). There was no relation between the slope of the ST segment or the magnitude of its deviation and the achievement of TIMI grade 3 flow. Only 20% of the 59 patients with both Q waves and T-wave inversion had TIMI grade 3 flow, compared with 50% of the remaining patients (p <0.0001). Among patients treated within 3 hours, TIMI grade 3 flow was seen in 68% of those without versus 44% of those with Q waves (p <0.01), and in 62% of those without versus 43% of those with T-wave inversion (p = 0.06). Among patients treated after 3 hours, TIMI grade 3 flow was seen in 38% of those without versus 30% of those with Q waves (p = NS), and in 38% of those without versus 23% of those with T-wave inversion (p <0.05). On multivariate analysis, the absence of Q waves, the time from the onset of chest pain to treatment, and age were independent predictors of TIMI grade 3 flow. Pathologic Q waves in the presenting electrocardiogram provide valuable information as to the probability of achieving successful reperfusion following administration of streptokinase, and may be helpful for triage of patients to alternative reperfusion strategies, including percutaneous revascularization.

  12. Non-invasive evaluation of myocardial reperfusion by transthoracic Doppler echocardiography and single-photon emission computed tomography in patients with anterior acute myocardial infarction.

    PubMed

    Sadauskiene, Egle; Zakarkaite, Diana; Ryliskyte, Ligita; Celutkiene, Jelena; Rudys, Alfredas; Aidietiene, Sigita; Laucevicius, Aleksandras

    2011-05-28

    The study was designed to evaluate whether the preserved coronary flow reserve (CFR) 72 hours after reperfused acute myocardial infarction (AMI) is associated with less microvascular dysfunction and is predictive of left ventricular (LV) functional recovery and the final infarct size at follow-up. In our study, CFR was assessed by transthoracic Doppler echocardiography (TDE) in 44 patients after the successful percutaneous coronary intervention during the acute AMI phase. CFR was correlated with contractile reserve assessed by low-dose dobutamine echocardiography and with the total perfusion defect measured by single-photon emission computed tomography 72 hours after reperfusion and at 5 months follow-up. The ROC analysis was performed to determine test sensitivity and specificity based on CFR. Categorical data were compared by an χ² analysis, continuous variables were analysed with the independent Student's t test. In order to analyse correlation between CFR and the parameters of LV function and perfusion, the Pearson correlation analysis was conducted. The linear regression analysis was used to assess the relationship between CFR and myocardial contractility as well as the final infarct size. We estimated the CFR cut-off value of 1.75 as providing the maximal accuracy to distinguish between patients with preserved and impaired CFR during the acute AMI phase (sensitivity 91.7%, specificity 75%). Wall motion score index was better in the subgroup with preserved CFR as compared to the subgroup with reduced CFR: 1.74 (0.29) vs. 1.89 (0.17) (p < 0.001) during the acute phase and 1.47 (0.30) vs. 1.81 (0.20) (p < 0.001) at follow-up, respectively. LV ejection fraction was 47.78% (8.99) in preserved CFR group vs. 40.79% (7.25) in impaired CFR group (p = 0.007) 72 hours after reperfusion and 49.78% (8.70) vs. 40.36% (7.90) (p = 0.001) after 5 months at follow-up, respectively. The final infarct size was smaller in patients with preserved as compared to patients with

  13. Non-invasive evaluation of myocardial reperfusion by transthoracic Doppler echocardiography and single-photon emission computed tomography in patients with anterior acute myocardial infarction

    PubMed Central

    2011-01-01

    Background The study was designed to evaluate whether the preserved coronary flow reserve (CFR) 72 hours after reperfused acute myocardial infarction (AMI) is associated with less microvascular dysfunction and is predictive of left ventricular (LV) functional recovery and the final infarct size at follow-up. Methods In our study, CFR was assessed by transthoracic Doppler echocardiography (TDE) in 44 patients after the successful percutaneous coronary intervention during the acute AMI phase. CFR was correlated with contractile reserve assessed by low-dose dobutamine echocardiography and with the total perfusion defect measured by single-photon emission computed tomography 72 hours after reperfusion and at 5 months follow-up. The ROC analysis was performed to determine test sensitivity and specificity based on CFR. Categorical data were compared by an χ2 analysis, continuous variables were analysed with the independent Student's t test. In order to analyse correlation between CFR and the parameters of LV function and perfusion, the Pearson correlation analysis was conducted. The linear regression analysis was used to assess the relationship between CFR and myocardial contractility as well as the final infarct size. Results We estimated the CFR cut-off value of 1.75 as providing the maximal accuracy to distinguish between patients with preserved and impaired CFR during the acute AMI phase (sensitivity 91.7%, specificity 75%). Wall motion score index was better in the subgroup with preserved CFR as compared to the subgroup with reduced CFR: 1.74 (0.29) vs. 1.89 (0.17) (p < 0.001) during the acute phase and 1.47 (0.30) vs. 1.81 (0.20) (p < 0.001) at follow-up, respectively. LV ejection fraction was 47.78% (8.99) in preserved CFR group vs. 40.79% (7.25) in impaired CFR group (p = 0.007) 72 hours after reperfusion and 49.78% (8.70) vs. 40.36% (7.90) (p = 0.001) after 5 months at follow-up, respectively. The final infarct size was smaller in patients with preserved as

  14. Comparison of regional and global left ventricular function by serial echocardiograms after reperfusion in acute myocardial infarction.

    PubMed

    Broderick, T M; Bourdillon, P D; Ryan, T; Feigenbaum, H; Dillon, J C; Armstrong, W F

    1989-01-01

    Fifty patients undergoing successful reperfusion therapy (percutaneous transluminal coronary angioplasty 20, thrombolysis 10, combined 20) for acute myocardial infarction were evaluated with serial two-dimensional echocardiograms performed early (less than 24 hours, mean 8 hours) and late (greater than 3 days, mean 6 days) after presentation. Treatment occurred within 12 hours of the onset of symptoms with most patients achieving reperfusion in less than 6 hours (mean 4.7 hours) from the onset of pain. Reperfusion was demonstrated short-term by angiography in 42 of 50 patients (84%). Four patients had clinical signs of reperfusion and subsequent angiographic confirmation. An additional four patients with "stuttering" infarct courses were treated late by percutaneous transluminal coronary angioplasty. Echocardiograms were analyzed for global performance by calculation of fractional area change at the papillary muscle level and ejection fraction (biplane Simpson's rule) in 18 patients in whom this analysis could be performed. Measurements of regional function included fractional shortening at the base (n = 37), regional wall motion index (n = 50) and percent of normal functioning myocardium (n = 50). Overall there was a significant improvement in regional wall scores and percent of functioning myocardium (regional wall motion index 1.73 to 1.43, p less than 0.001 and percent of functioning myocardium 0.61 to 0.70, p less than 0.001) but only a trend toward improvement when global function was assessed by ejection fraction (0.42 to 0.48, p less than 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Effect of charted mental illness on reperfusion therapy in hospitalized patients with an acute myocardial infarction in Florida

    PubMed Central

    Campi, Thomas R.; George, Sharon; Villacís, Diego; Ward-Peterson, Melissa; Barengo, Noël C.; Zevallos, Juan C.

    2017-01-01

    Abstract Patients with mental illness carry risk factors that predispose them to excess cardiovascular mortality from an acute myocardial infarction (AMI) compared to the general population. The aim of this study was to determine if patients with AMI and charted mental illness (CMI) received less reperfusion therapy following an AMI, compared to AMI patients without CMI in a recent sample population from Florida. A secondary analysis of data was conducted using the Florida Agency for Health Care Administration (FL-AHCA) hospital discharge registry. Adults hospitalized with an AMI from 01/01/2010 to 12/31/2015 were included for the analysis. The dependent variable was administration of reperfusion therapy (thrombolytic, percutaneous coronary intervention [PCI], and coronary artery bypass graft [CABG]), and the independent variable was the presence of CMI (depression, schizophrenia, and bipolar disorder). Multivariate logistic regression models were used to test the association controlling for age, gender, ethnicity, race, health insurance, and comorbidities. The database included 61,614 adults (31.3% women) hospitalized with AMI in Florida. The CMI population comprised of 1036 patients (1.7%) who were on average 5 years younger than non-CMI (60.2 ±12.8 versus 65.2 ±14.1; P < .001). Compared with patients without CMI, patients with CMI had higher proportions of women, governmental health insurance holders, and those with more comorbidities. The adjusted odds ratio indicated that patients with CMI were 30% less likely to receive reperfusion therapy compared with those without CMI (OR = 0.7; 95% CI = 0.6–0.8). Within the AMI population including those with and without CMI, women were 23% less likely to receive therapy than men; blacks were 26% less likely to receive reperfusion therapy than whites; and those holding government health insurances were between 20% and 40% less likely to receive reperfusion therapy than those with private health

  16. Effect of charted mental illness on reperfusion therapy in hospitalized patients with an acute myocardial infarction in Florida.

    PubMed

    Campi, Thomas R; George, Sharon; Villacís, Diego; Ward-Peterson, Melissa; Barengo, Noël C; Zevallos, Juan C

    2017-08-01

    Patients with mental illness carry risk factors that predispose them to excess cardiovascular mortality from an acute myocardial infarction (AMI) compared to the general population. The aim of this study was to determine if patients with AMI and charted mental illness (CMI) received less reperfusion therapy following an AMI, compared to AMI patients without CMI in a recent sample population from Florida.A secondary analysis of data was conducted using the Florida Agency for Health Care Administration (FL-AHCA) hospital discharge registry. Adults hospitalized with an AMI from 01/01/2010 to 12/31/2015 were included for the analysis. The dependent variable was administration of reperfusion therapy (thrombolytic, percutaneous coronary intervention [PCI], and coronary artery bypass graft [CABG]), and the independent variable was the presence of CMI (depression, schizophrenia, and bipolar disorder). Multivariate logistic regression models were used to test the association controlling for age, gender, ethnicity, race, health insurance, and comorbidities.The database included 61,614 adults (31.3% women) hospitalized with AMI in Florida. The CMI population comprised of 1036 patients (1.7%) who were on average 5 years younger than non-CMI (60.2 ±12.8 versus 65.2 ±14.1; P < .001). Compared with patients without CMI, patients with CMI had higher proportions of women, governmental health insurance holders, and those with more comorbidities. The adjusted odds ratio indicated that patients with CMI were 30% less likely to receive reperfusion therapy compared with those without CMI (OR = 0.7; 95% CI = 0.6-0.8). Within the AMI population including those with and without CMI, women were 23% less likely to receive therapy than men; blacks were 26% less likely to receive reperfusion therapy than whites; and those holding government health insurances were between 20% and 40% less likely to receive reperfusion therapy than those with private health insurance

  17. Myocardial ischemia reperfusion injury: from basic science to clinical bedside.

    PubMed

    Frank, Anja; Bonney, Megan; Bonney, Stephanie; Weitzel, Lindsay; Koeppen, Michael; Eckle, Tobias

    2012-09-01

    Myocardial ischemia reperfusion injury contributes to adverse cardiovascular outcomes after myocardial ischemia, cardiac surgery or circulatory arrest. Primarily, no blood flow to the heart causes an imbalance between oxygen demand and supply, named ischemia (from the Greek isch, restriction; and haema, blood), resulting in damage or dysfunction of the cardiac tissue. Instinctively, early and fast restoration of blood flow has been established to be the treatment of choice to prevent further tissue injury. Indeed, the use of thrombolytic therapy or primary percutaneous coronary intervention is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. Unfortunately, restoring blood flow to the ischemic myocardium, named reperfusion, can also induce injury. This phenomenon was therefore termed myocardial ischemia reperfusion injury. Subsequent studies in animal models of acute myocardial infarction suggest that myocardial ischemia reperfusion injury accounts for up to 50% of the final size of a myocardial infarct. Consequently, many researchers aim to understand the underlying molecular mechanism of myocardial ischemia reperfusion injury to find therapeutic strategies ultimately reducing the final infarct size. Despite the identification of numerous therapeutic strategies at the bench, many of them are just in the process of being translated to bedside. The current review discusses the most striking basic science findings made during the past decades that are currently under clinical evaluation, with the ultimate goal to treat patients who are suffering from myocardial ischemia reperfusion-associated tissue injury.

  18. Temporal change of enhancement after gadolinium injection on contrast-enhanced CMR in reperfused acute myocardial infarction.

    PubMed

    Matsumoto, Hidenari; Matsuda, Tetsuya; Miyamoto, Kenichi; Shimada, Toshihiko; Ushimaru, Shunpei; Mikuri, Mikiko; Yamazaki, Taketoshi

    2015-01-01

    A recent report demonstrated that early enhancement on contrast-enhanced cardiac magnetic resonance (CE-CMR) correlated with myocardial edema detected by T2-weighted CMR in reperfused acute myocardial infarction (AMI). However, the time at which the enhancement in salvaged myocardium disappears is yet to be determined. We aimed to examine the time course of the enhancement with the use of different quantification techniques and to compare the extent of enhancement with the myocardial edema. CE-CMR was performed at 2-20 min after gadolinium administration in 32 AMI patients. The extent of enhancement (% myocardium) was quantified by manual delineation and the threshold methods of 2-5 SDs above remote myocardium. In subendocardial infarct, the enhancement was greatest at 2 min regardless of the quantification techniques and decreased with time, particularly in the first 6 min. In transmural infarct, the change in the size of enhancement was modest although the time course of enhancement varied according to the quantification techniques. The sizes of enhancement were not significantly different between 15 and 20 min regardless of the techniques and infarct transmurality. The best agreement with myocardial edema was found at 2 min with average differences of 0.5% and -1.2% and limits of agreement of ±20.2% and ±21.2% for the manual and 2-SD techniques, respectively. The optimal timing for delineation of salvaged myocardium on CE-CMR is at 2min when the manual or 2-SD technique was employed. Imaging needs to be completed in a short time (ideally within a minute) because of rapid reduction of enhancement in salvaged myocardium. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  19. Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial.

    PubMed

    Kloner, Robert A; Forman, Mervyn B; Gibbons, Raymond J; Ross, Allan M; Alexander, R Wayne; Stone, Gregg W

    2006-10-01

    The purpose of this analysis was to determine whether the efficacy of adenosine vs. placebo was dependent on the timing of reperfusion therapy in the second Acute Myocardial Infarction Study of Adenosine (AMISTAD-II). Patients presenting with ST-segment elevation anterior AMI were randomized to receive placebo vs. adenosine (50 or 70 microg/kg/min) for 3 h starting within 15 min of reperfusion therapy. In the present post hoc hypothesis generating study, the results were stratified according to the timing of reperfusion, i.e. > or = or < the median 3.17 h, and by reperfusion modality. In patients receiving reperfusion < 3.17 h, adenosine compared with placebo significantly reduced 1-month mortality (5.2 vs. 9.2%, respectively, P = 0.014), 6-month mortality (7.3 vs. 11.2%, P = 0.033), and the occurrence of the primary 6-month composite clinical endpoint of death, in-hospital CHF, or rehospitalization for CHF at 6 months (12.0 vs. 17.2%, P = 0.022). Patients reperfused beyond 3 h did not benefit from adenosine. In this post hoc analysis, 3 h adenosine infusion administered as an adjunct to reperfusion therapy within the first 3.17 h onset of evolving anterior ST-segment elevation AMI enhanced early and late survival, and reduced the composite clinical endpoint of death or CHF at 6 months.

  20. SDF-1/CXCR4 mediates acute protection of cardiac function through myocardial STAT3 signaling following global ischemia/reperfusion injury

    PubMed Central

    Huang, Chunyan; Gu, Hongmei; Zhang, Wenjun; Manukyan, Mariuxi C.; Shou, Weinian

    2011-01-01

    Stromal cell-derived factor-1α (SDF-1) has been reported to mediate cardioprotection through the mobilization of stem cells into injured tissue and an increase in local angiogenesis after myocardial infarction. However, little is known regarding whether SDF-1 induces acute protection following global myocardial ischemia/reperfusion (I/R) injury and if so, by what molecular mechanism. SDF-1 binding to its cognate receptor CXCR4 has been shown to activate STAT3 in a variety of cells. STAT3 is a cardioprotective factor and may mediate SDF-1/CXCR4-induced acute protection. We hypothesized that SDF-1 would improve myocardial function through CXCR4-increased STAT3 activation following acute I/R. Isolated mouse hearts were subjected to 25-min global ischemia/40-min reperfusion and divided into groups of 1) vehicle; 2) SDF-1; 3) AMD3100, a CXCR4 inhibitor; 4) SDF-1 + AMD3100; 5) Stattic, a STAT3 inhibitor; 6) SDF-1 + Stattic; 7) cardiomyocyte-restricted ablation of STAT3 (STAT3KO); 8) STAT3KO + SDF-1; 9) Ly294002, an inhibitor of the Akt pathway; and 10) SDF-1 + Ly294002. Reagents were infused into hearts within 5 min before ischemia. SDF-1 administration significantly improved postischemic myocardial functional recovery in a dose-dependent manner. Additionally, pretreatment with SDF-1 reduced cardiac apoptotic signaling and increased myocardial STAT3 activation following acute I/R. Inhibition of the SDF-1 receptor CXCR4 neutralized these protective effects by SDF-1 in hearts subjected to I/R. Notably, inhibition of the STAT3 pathway or use of STAT3KO hearts abolished SDF-1-induced acute protection following myocardial I/R. Our results represent the first evidence that the SDF-1/CXCR4 axis upregualtes myocardial STAT3 activation and, thereby, mediates acute cardioprotection in response to global I/R. PMID:21821779

  1. Damas hospital compliance to American College of Cardiology reperfusion therapy during acute ST-elevation myocardial infarction.

    PubMed

    Beauchamp-Irizarry, Ana; Gómez-Rivera, José; Bredy Domínguez, Rafael

    2012-01-01

    Despite improvements in care, up to one-third of patients presenting with ST-elevation myocardial infarction (STEMI) within 12 hours of symptom onset receive no reperfusion therapy. Despite effective pre- and in-hospital reperfusion strategies becoming standard over the past two decades, time-to-admission and time-to-treatment remains prolonged. Prompt reperfusion treatment is essential to decrease mortality. The ACC/AHA guidelines recommend that the interval between arrival at the hospital and intracoronary balloon inflation during percutaneous coronary intervention should be within ninety minutes of patient arrival to the ED or less and within 30 minutes for fibrinolytic therapy. However, few hospitals meet this objective. We did a retrospective analysis of patients with STEMI from January 2008 to December 2010. From an initial list of 57 patients, only 45 patients presented with confirmed STEMI. Of these, 35 had indication for reperfusion therapy. 97% received fibrinolytic therapy versus 3% who underwent percutaneous coronary intervention (PCI). The reperfusion time goal was achieved in 45% of cases treated with fibrinolytic therapy. Most of the patients presenting with STEMI undergo reperfusion therapy with fibrinolytic therapy. PCI was not performed as initial reperfusion therapy, even at regular duty hours. Reperfusion therapy was performed beyond the expected time goal in more that half of the cases. The most significant delay was related to nursing staff performance.

  2. The Antioxidant, N-(2-mercaptopropionyl)-glycine (MPG), Does Not Reduce Myocardial Infarct Size in an Acute Canine Model of Myocardial Ischemia and Reperfusion.

    PubMed

    Venturini; Flickinger; Womack; Smith; McMahon

    1998-05-01

    Oxygen radical generation can be measured when blood flow is restored to previously ischemic tissue. Although several studies have suggested oxygen radicals contribute to lethal injury of myocardium after ischemia, other studies have failed to confirm this implication. Antioxidants, such as N-(2-mercaptoptopionyl)-glycine (MPG) and superoxide dismutase, have had inconsistent effects on lethal myocardial injury in animal models of ischemia and reperfusion. Many variables influence lethal myocardial injury in these models: time of ischemia, time of reperfusion, dose of antioxidant, myocardial oxygen demand, area at risk, collateral blood flow, and body core temperature. The purpose of this study is to test the effects of infusion of MPG on lethal reperfusion injury in a canine model of ischemia and reperfusion with these variables tightly controlled. The left anterior descending coronary artery of anesthetized dogs was ligated for 90 minutes and reperfused for 4 hours. MPG was infused (100 mg/kg/h) 15 minutes before the end of ischemia and throughout reperfusion. Core body temperature was closely monitored, and infarct size was adjusted to transmural myocardial blood flow during ischemia. MPG had no effect on infarct size or infarct size adjusted for changes in collateral blood flow. These data reinforce a general difficulty in demonstrating the effects of antioxidant therapies on lethal injury, even when closely monitoring covariates known to impact infarct size.

  3. Acute insulin resistance in ST-segment elevation myocardial infarction in non-diabetic patients is associated with incomplete myocardial reperfusion and impaired coronary microcirculatory function

    PubMed Central

    2014-01-01

    acute phase of the first anterior STEMI in patients without diabetes treated by pPCI is independently associated with poorer myocardial reperfusion, impaired coronary microcirculatory function and potentially with larger final infarct size. PMID:24708817

  4. Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology.

    PubMed

    Feng, Yuanbo; Chen, Feng; Yin, Ting; Xia, Qian; Liu, Yewei; Huang, Gang; Zhang, Jian; Oyen, Raymond; Ni, Yicheng

    2015-10-01

    Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P < 0.05), significantly increased blood flow in the AAR (P < 0.05), significantly decreased microvascular obstruction (P < 0.05), increased the perfusion density rate by 1.7-fold, lowered the AMI core/AAR ratio (P < 0.05), and increased the myocardial salvage index (P < 0.05). These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis (P < 0.05). Thus, CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility.

  5. Altered myocardial glucose utilization and the reverse mismatch pattern on rubidium-82 perfusion/F-18-FDG PET during the sub-acute phase following reperfusion of acute anterior myocardial infarction.

    PubMed

    Anselm, Daniel D; Anselm, Anjali H; Renaud, Jennifer; Atkins, Harold L; de Kemp, Robert; Burwash, Ian G; Williams, Kathryn A; Guo, Ann; Kelly, Cathy; Dasilva, Jean; Beanlands, Rob S B; Glover, Christopher A

    2011-08-01

    Reperfused myocardium post-acute myocardial infarction (AMI) may have altered metabolism with implications for therapy response and function recovery. We explored glucose utilization and the "reverse mismatch" (RMM) pattern (decreased F-18-fluorodeoxyglucose (FDG) uptake relative to perfusion) in patients who underwent mechanical reperfusion with percutaneous coronary intervention (PCI) for AMI. Thirty-one patients with anterior wall AMI treated with acute reperfusion, with left ventricular ejection fraction ≤45%, underwent rest rubidium-82 (Rb-82) and FDG PET 2-10 days post-AMI. Resting echocardiograms were used to assess wall motion abnormalities. Significant RMM occurred in 15 (48%) patients and was associated with a shorter time to PCI of 2.9 hours (2.2, 13.3 hours) compared to patients without significant RMM: 11.4 hours (3.9, 22.4 hours) (P = .03). Within the peri-infarct regions, segments with significant RMM were more likely to have wall motion abnormalities (OR = 2.3 (1.1, 4.7), P = .02) compared to segments without significant RMM. RMM is a common pattern on perfusion/FDG PET during the sub-acute phase following reperfusion of AMI and is associated with shorter times to PCI. Within the peri-infarct region, RMM occurs frequently and is more often associated with wall motion abnormalities than segments without RMM. Whether this represents a myocardial metabolic shift during the sub-acute phase of recovery warrants further study.

  6. Bloodless reperfusion with the oxygen carrier HBOC-201 in acute myocardial infarction: a novel platform for cardioprotective probes delivery.

    PubMed

    García-Ruiz, Jose M; Galán-Arriola, Carlos; Fernández-Jiménez, Rodrigo; Aguero, Jaume; Sánchez-González, Javier; García-Alvarez, Ana; Nuno-Ayala, Mario; Dubé, Gregory P; Zafirelis, Zafiris; López-Martín, Gonzalo J; Bernal, Juan A; Lara-Pezzi, Enrique; Fuster, Valentín; Ibáñez, Borja

    2017-03-01

    Reperfusion, despite being required for myocardial salvage, is associated with additional injury. We hypothesize that infarct size (IS) will be reduced by a period of bloodless reperfusion with hemoglobin-based oxygen carriers (HBOC) before blood-flow restoration. In the pig model, we first characterized the impact of intracoronary perfusion with a fixed volume (600 ml) of a pre-oxygenated acellular HBOC, HBOC-201, on the healthy myocardium. HBOC-201 was administered through the lumen of the angioplasty balloon (i.e., distal to the occlusion site) immediately after onset of coronary occlusion at 1, 0.7, 0.4, or 0.2 ml/kg/min for 12, 17, 30, and 60 min, respectively, followed by blood-flow restoration. Outcome measures were systemic hemodynamics and LV performance assessed by the state-of-the-art cardiac magnetic resonance (CMR) imaging. The best performing HBOC-201 perfusion strategies were then tested for their impact on LV performance during myocardial infarction, in pigs subjected to 45 min mid-left anterior descending (LAD) coronary occlusion. At the end of the ischemia duration, pigs were randomized to regular reperfusion (blood-only reperfusion) vs. bloodless reperfusion (perfusion with pre-oxygenated HBOC-201 distal to the occlusion site), followed by blood-flow restoration. Hemodynamics and CMR-measured LV performance were assessed at 7- and 45-day follow-up. In modifications of the HBOC-201 procedure, glucose and insulin were included to support cardiac metabolism. A total of 66 pigs were included in this study. Twenty healthy pigs (5 per infusion protocol) were used in the study of healthy myocardium. Intracoronary administration of HBOC-201 (600 ml) at varying rates, including a flow of 0.4 ml/kg/min (corresponding to a maximum perfusion time of 30 min), did not damage the healthy myocardium. Slower perfusion (longer infusion time) was associated with permanent LV dysfunction and myocardial necrosis. A total of 46 pigs underwent MI induction

  7. Iloprost and vitamin C attenuates acute myocardial injury induced by suprarenal aortic ischemia-reperfusion in rabbits.

    PubMed

    Iriz, E; Iriz, A; Take, G; Ozgul, H; Oktar, L; Demirtas, H; Helvacioglu, F; Arslan, M

    2015-01-01

    The aim of this study was to evaluate antioxidant and cytoprotective effects of iloprost and Vitamin C in a distant organ after abdominal aorta ischemia-reperfusion injury. Twenty-eight New Zealand rabbits weighing 2,400-2,800 g were used for this study. The rabbits were divided into four equal groups. These groups are control group, sham group, iloprost group, and iloprost+vitamin C group. Suprarenal aorta was occluded with a vascular clamp. Following 30 minutes of ischemia, the vascular clamp was removed. Rabbits in group 3 received 10 ng/kg/min iloprost and those in group 4 received 10 ng/kg/min iloprost and 10 mg/kg vitamin C. At the end of the reperfusion period, the rabbits were sacrificed by a high intraperitoneal dose of xylazine+ketamine injection. Myocardial tissue samples were taken for electron microscopic analysis. We evaluated SOD, MDA and catalase in myocardial tissue samples. Iloprost and iloprost+vitamin C groups significantly reduced the oxidative stress markers in tissue samples (p<0.05) and significantly decreased the myofibrillar injury and mitochondrial morphology changes in the myocardial tissue as shown with electron microscopy (p<0.05). Myocardial edema was significantly alleviated by iloprost and iloprost+vitamin C administration (p<0.05). This study clearly showed that myocardial injury and edema occurred after ischemia-reperfusion of abdominal aorta and that groups administered with iloprost and iloprost+vitamin C showed an attenuation of ischemia-reperfusion injury in distant organs (Tab. 3, Fig. 4, Ref. 30).

  8. Antiarrhythmic activity of n-tyrosol during acute myocardial ischemia and reperfusion.

    PubMed

    Chernyshova, G A; Plotnikov, M B; Smol'yakova, V I; Golubeva, I V; Aliev, O I; Tolstikova, T G; Krysin, A P; Sorokina, I V

    2007-06-01

    Antiarrhythmic activity of n-tyrosol was demonstrated on the model of early occlusion and reperfusion arrhythmia. The preparation reduces the incidence of ventricular tachycardia and fibrillation, increases the percent of animals without ventricular arrhythmia, and moderates the severity of developing ventricular arrhythmias.

  9. Acute myocardial infarction.

    PubMed

    Boersma, Eric; Mercado, Nestor; Poldermans, Don; Gardien, Martin; Vos, Jeroen; Simoons, Maarten L

    2003-03-08

    Acute myocardial infarction is a common disease with serious consequences in mortality, morbidity, and cost to the society. Coronary atherosclerosis plays a pivotal part as the underlying substrate in many patients. In addition, a new definition of myocardial infarction has recently been introduced that has major implications from the epidemiological, societal, and patient points of view. The advent of coronary-care units and the results of randomised clinical trials on reperfusion therapy, lytic or percutaneous coronary intervention, and chronic medical treatment with various pharmacological agents have substantially changed the therapeutic approach, decreased in-hospital mortality, and improved the long-term outlook in survivors of the acute phase. New treatments will continue to emerge, but the greatest challenge will be to effectively implement preventive actions in all high-risk individuals and to expand delivery of acute treatment in a timely fashion for all eligible patients.

  10. A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model.

    PubMed

    Ichimura, Kenzo; Matoba, Tetsuya; Nakano, Kaku; Tokutome, Masaki; Honda, Katsuya; Koga, Jun-Ichiro; Egashira, Kensuke

    2016-01-01

    There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic modality for IR injury in acute myocardial

  11. A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model

    PubMed Central

    Ichimura, Kenzo; Matoba, Tetsuya; Nakano, Kaku; Tokutome, Masaki; Honda, Katsuya; Koga, Jun-ichiro; Egashira, Kensuke

    2016-01-01

    Background There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. Methods and Results Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. Conclusions NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic

  12. T2-weighted cardiac MR assessment of the myocardial area-at-risk and salvage area in acute reperfused myocardial infarction: comparison of state-of-the-art dark blood and bright blood T2-weighted sequences.

    PubMed

    Viallon, Magalie; Mewton, Nathan; Thuny, Franck; Guehring, Jens; O'Donnell, Thomas; Stemmer, Alto; Bi, Xiaoming; Rapacchi, Stanislas; Zuehlsdorff, Sven; Revel, Didier; Croisille, Pierre

    2012-02-01

    To compare different state-of-the-art T2-weighted (T2w) imaging sequences combined with late gadolinium enhancement (LGE) for myocardial salvage area (MSA) assessment by cardiac magnetic resonance (CMR). T2w imaging has been used to assess the myocardial area at risk (AAR) in acute myocardial infarction (AMI) patients, but its clinical application is challenging due to technical and physical limitations. Thirty patients with reperfused AMI underwent complete CMR imaging 2-5 days after hospital admission. Myocardial AAR and MSA were quantified on four different T2w sequences: (a) free-breathing T2-prepared single-shot balanced steady-state free precession (T2p_ssbSSFP); (b) breathhold T2-weighted acquisition for cardiac unified T2 edema (ACUTE); (c) breathhold T2w dark-blood inversion recovery turbo-spin echo (IR-TSE) (short-term inversion recovery: STIR); and (d) free-breathing high-resolution T2 dark-blood navigated BLADE. The diagnostic performance of each technique was also assessed. Quantitative analysis showed significant differences in myocardial AAR extent as quantified by the four T2w sequences (P < 0.05). There were also significant differences in sensitivity, specificity and overall diagnostic performance. Detection and quantification of AAR, and thus of MSA, by T2wCMR in reperfused AMI patients varied significantly between different T2w sequences in the same clinical setting. Copyright © 2011 Wiley Periodicals, Inc.

  13. Magnetic Resonance Imaging of Acute Reperfused Myocardial Infarction: Intraindividual Comparison of ECIII-60 and Gd-DTPA in a Swine Model

    SciTech Connect

    Jin Jiyang; Teng Gaojun; Feng Yi; Wu Yanping; Jin Qindi; Wang Yu; Wang Zhen; Lu Qin; Jiang Yibo; Wang Shengqi; Chen Feng; Marchal, Guy; Ni Yicheng

    2007-04-15

    Purpose. To compare a necrosis-avid contrast agent (NACA) bis-Gd-DTPA-pamoic acid derivative (ECIII-60) after intracoronary delivery with an extracellular agent Gd-DTPA after intravenous injection on magnetic resonance imaging (MRI) in a swine model of acute reperfused myocardial infarction (MI). Methods. Eight pigs underwent 90 min of transcatheter coronary balloon occlusion and 60 min of reperfusion. After intravenous injection of Gd-DTPA at a dose of 0.2 mmol/kg, all pigs were scanned with T1-weighted MRI until the delayed enhancement of MI disappeared. Then they were intracoronarily infused with ECIII-60 at 0.0025 mmol/kg and imaged for 5 hr. Signal intensity, infarct-over-normal contrast ratio and relative infarct size were quantified, compared, and correlated with the results of postmortem MRI and triphenyltetrazolium chloride (TTC) histochemical staining. Results. A contrast ratio over 3.0 was induced by both Gd-DTPA and ECIII-60. However, while the delayed enhancement with Gd-DTPA virtually vanished in 1 hr, ECIII-60 at an 80x smaller dose depicted the MI accurately over 5 hr as proven by ex vivo MRI and TTC staining. Conclusion. Both Gd-DTPA and ECIII-60 strongly enhanced acute MI. Comparing with fading contrast in a narrow time window with intravenous Gd-DTPA, intracoronary ECIII-60 persistently demarcated the acute MI, indicating a potential method for postprocedural assessment of myocardial viability after coronary interventions.

  14. Protective approaches against myocardial ischemia reperfusion injury

    PubMed Central

    Li, Xianchi; Liu, Min; Sun, Rongrong; Zeng, Yi; Chen, Shuang; Zhang, Peiying

    2016-01-01

    Myocardial ischemia-reperfusion is the leading cause for the events of cardiovascular disease, and is considered as a major contributor to the morbidity and mortality associated with coronary occlusion. The myocardial damage caused by ischemia-reperfusion injury constitutes the primary pathological manifestation of coronary artery disease. It results from the interaction between the substances that accumulate during ischemia and those that are delivered on reperfusion. The level of this damage can range from a small insult resulting in limited myocardial damage to a large injury culminating in myocyte death. Importantly, major ischemia-reperfusion injury to the heart can result in permanent disability or death. Given the worldwide prevalence of coronary artery disease, developing a strategy to provide cardioprotection against ischemia-reperfusion-induced damage is of great importance. Currently, the treatment of reperfusion injury following ischemia is primarily supportive, since no specific target-oriented therapy has been validated thus far. Nevertheless, therapeutic approaches to protect against myocardial ischemia-reperfusion injury remain an active area of investigation given the detrimental effects of this phenomenon. PMID:28101167

  15. Enzymatic evidence of impaired reperfusion in diabetic patients after thrombolytic therapy for acute myocardial infarction: a role for plasminogen activator inhibitor?

    PubMed Central

    Gray, R P; Yudkin, J S; Patterson, D L

    1993-01-01

    OBJECTIVE--To compare the activity of plasminogen activator inhibitor (PAI-1) in diabetic and non-diabetic patients admitted with acute myocardial infarction and to determine whether PAI-1 activity influences reperfusion after thrombolytic therapy. DESIGN--Prospective study of patients admitted with acute myocardial infarction. SETTING--District general hospital. MAIN OUTCOME MEASURES--Reperfusion assessed by time to peak release of creatine kinase-MB isoenzyme. RESULTS--Baseline PAI-1 activity and antigen concentrations were significantly higher in diabetic patients (n = 45) than in non-diabetic patients (n = 110) (24.6 (6.9) v 18.6 (7.9) AU/ml (AU = arbitrary units) (p = 0.0001) and 58.8 (13.1-328.8) v 41.0 (10.9-125.4) ng/ml (p = 0.004). Time to peak release of creatine kinase-MB was calculated in 123 (80%) patients. In 98 who received thrombolytic therapy the median time to peak enzyme release was 15.5 h (7.5-24 h) in diabetic patients (n = 26) and 12 h (5-26 h) in non-diabetic patients (n = 72) (p = 0.005). In those with a time to peak release of < or = 12 h, indicating likely successful reperfusion, PAI-1 activity was 17.5 (7.8) AU/ml compared with 22.8 (7.7) AU/ml in those with a time to peak release of > 12 h (p = 0.001). In multiple regression analysis both diabetes (p = 0.0001) and PAI-1 activity at admission (p = 0.029) were independently related to successful reperfusion. In 13 patients with evidence of reinfarction in hospital PAI-1 activity on day 3 was 26.7 (6.4) AU/ml compared with 21.7 (6.3) AU/ml in those without evidence of reinfarction (p = 0.032). CONCLUSION--Both raised PAI-1 activity on admission and diabetes were associated with a reduced likelihood of enzymatic evidence of reperfusion after thrombolytic therapy. Increased PAI-1 activity on day 3 was associated with an increased risk of reinfarction. Diabetic patients had higher PAI-1 activity on admission. This may partly explain their reduced likelihood of reperfusion. PMID:8280517

  16. Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction).

    PubMed

    Pizarro, Gonzalo; Fernández-Friera, Leticia; Fuster, Valentin; Fernández-Jiménez, Rodrigo; García-Ruiz, José M; García-Álvarez, Ana; Mateos, Alonso; Barreiro, María V; Escalera, Noemí; Rodriguez, Maite D; de Miguel, Antonio; García-Lunar, Inés; Parra-Fuertes, Juan J; Sánchez-González, Javier; Pardillos, Luis; Nieto, Beatriz; Jiménez, Adriana; Abejón, Raquel; Bastante, Teresa; Martínez de Vega, Vicente; Cabrera, José A; López-Melgar, Beatriz; Guzman, Gabriela; García-Prieto, Jaime; Mirelis, Jesús G; Zamorano, José Luis; Albarrán, Agustín; Goicolea, Javier; Escaned, Javier; Pocock, Stuart; Iñiguez, Andrés; Fernández-Ortiz, Antonio; Sánchez-Brunete, Vicente; Macaya, Carlos; Ibanez, Borja

    2014-06-10

    The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction

  17. Variation of plasma levels of endothelin, calcitonin gene-related peptide, nitric oxide, and malondialdehyde in acute myocardial ischemia reperfusion injury in a rabbit model.

    PubMed

    Zhao, Y B; Wang, Y Z; Yue, Y H; Zhao, W C; Feng, G X

    2015-05-25

    We examined the variation in plasma levels of endothelin (ET), calcitonin gene-related peptide (CGRP), nitric oxide (NO), and malondialdehyde (MDA), as well as superoxide dismutase (SOD) activity, in acute myocardial ischemia reperfusion injury in a rabbit model. Seventy rabbits were randomly assigned into 3 groups. Open-chest surgery (OCS) was performed for all rabbits. Group A (N = 20) received sham-surgery, group B (N = 25) was the reperfusion group, and group C (N = 25) was the infarction group. At 12 h after chest clo-sure, plasma ET levels in groups B and C were clearly increased, while CGRP levels were clearly decreased, particularly in group B. At 24 h after chest closure, ET levels were higher than before OCS, while there was no significant difference between groups B and C. ET in group B was decreased, while that in group C was increased at 12 h. No significant difference in CGRP was observed between 12 and 24 h after chest closure. NO levels in groups B and C at 12 h after chest closure were significantly decreased compared to those before OCS. NO levels in group B at 24, 48, and 72 h were significantly lower than those at 12 h, while those of group C were not significantly changed after 12 h. Dynamic monitoring and comparison of plasma levels of ET, CGRP, NO, and MDA as well as SOD activity revealed that appropriate intervention of these factors may reduce reperfusion injury.

  18. Prognostic value and determinants of a hypointense infarct core in T2-weighted cardiac magnetic resonance in acute reperfused ST-elevation-myocardial infarction.

    PubMed

    Eitel, Ingo; Kubusch, Konrad; Strohm, Oliver; Desch, Steffen; Mikami, Yoko; de Waha, Suzanne; Gutberlet, Matthias; Schuler, Gerhard; Friedrich, Matthias G; Thiele, Holger

    2011-07-01

    A hypointense core of infarcted myocardium in T2-weighted cardiovascular MRI (CMR) has been used as a noninvasive marker for intramyocardial hemorrhage. However, the clinical significance of such findings not yet been established. The aim of this study was to evaluate determinants and prognostic impact of a hypointense infarct core in T2-weighted CMR images, studied in patients after acute, reperfused ST-elevation-myocardial infarction. We analyzed 346 patients with ST-elevation-myocardial infarction undergoing primary angioplasty < 12 hours after symptoms onset. T2-weighted, contrast-enhanced CMR was used for assessment of the area at risk, myocardial salvage, infarct size, hypointense core in T2-weighted images, and late microvascular obstruction. Patients were categorized into 2 groups defined by the presence or absence of a hypointense core. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and congestive heart failure within 6 months after infarction. A hypointense core was present in 122 (35%) patients and was associated with larger infarcts, greater amount of microvascular obstruction, less myocardial salvage, and impaired left ventricular function (P < 0.001, respectively). The presence of a hypointense core was a strong univariable predictor of major adverse cardiovascular events (hazard ratio, 2.59; confidence interval, 1.27 to 5.27) and was significantly associated with an increased major adverse cardiovascular events rate (16.4% versus 7.0%, P = 0.006) 6 months after infarction. A hypointense infarct core within the area at risk of reperfused infarcted myocardium in T2-weighted CMR is closely related to infarct size, microvascular obstruction, and impaired left ventricular function, with subsequent adverse clinical outcome.

  19. Ultrasound-Mediated Stimulation of Microbubbles after Acute Myocardial Infarction and Reperfusion Ameliorates Left-Ventricular Remodelling in Mice via Improvement of Borderzone Vascularization

    PubMed Central

    Dörner, Jonas; Struck, Rafael; Zimmer, Sebastian; Peigney, Christine; Duerr, Georg Daniel; Dewald, Oliver; Kim, Se-Chan; Malan, Daniela; Bettinger, Thierry; Nickenig, Georg; Ghanem, Alexander

    2013-01-01

    Aims Post-infarction remodelling (PIR) determines left-ventricular (LV) function and prognosis after myocardial infarction. The aim of this study was to evaluate transthoracic ultrasound-mediated microbubble stimulation (UMS) as a novel gene- and cell-free therapeutic option after acute myocardial infarction and reperfusion (AMI/R) in mice. Methods and Results For myocardial delivery of UMS, a novel therapeutic ultrasound-system (TIPS, Philips Medical) and commercially available microbubbles (BR1, Bracco Suisse SA) were utilized in a closed-chest mouse model. UMS was performed as myocardial post-conditioning (PC) on day four after 30 minutes of coronary occlusion and reperfusion. LV-morphology, as well as global and regional function were measured repeatedly with reconstructive 3-dimensional echocardiography applying an additional low-dose dobutamine protocol after two weeks. Scar size was quantified by means of histomorphometry. A total of 41 mice were investigated; 17 received PC with UMS. Mean ejection fraction (EF) prior UMS was similar in both groups 53%±10 (w/o UMS) and 53%±14 (UMS, p = 0.5), reflecting comparable myocardial mass at risk 17%±8 (w/o UMS), 16%±13 (UMS, p = 0.5). Two weeks after AMI/R, mice undergoing UMS demonstrated significantly better global LV-function (EF = 53%±7) as compared to the group without PC (EF = 39%±11, p<0.01). The fraction of akinetic myocardial mass was significantly lower among mice undergoing UMS after AMI/R [27%±10 (w/o UMS), 13%±8 (UMS), p<0.001)]. Our experiments showed a fast onset of transient, UMS-induced upregulation of vascular-endothelial and insulin-like growth factor (VEGF-a, IGF-1), as well as caveolin-3 (Cav-3). The mice undergoing PC with UMS after AMI/R showed a significantly lower scar size. In addition, the microvascular density was significantly higher in the borderzone of UMS-treated animals. Conclusion UMS following AMI/R ameliorates PIR in mice via up-regulation of VEGF-a, IGF-1

  20. Comparison of early myocardial technetium-99m pyrophosphate uptake to early peaking of creatine kinase and creatine kinase-MB as indicators of early reperfusion in acute myocardial infarction

    SciTech Connect

    Kondo, M.; Yuzuki, Y.; Arai, H.; Shimizu, K.; Morikawa, M.; Shimono, Y.

    1987-10-01

    The value of technetium-99m pyrophosphate (Tc-99m-PYP) scintigraphy as an indicator of reperfusion 2.8 to 8 hours after the onset of symptoms of acute myocardial infarction was compared with the value of early peak creatine kinase (CK) and CK-MB release within 16 hours after the onset of symptoms. In 29 patients who received thrombolytic therapy, recanalization was seen (group 1) and in 7 it was not (group 2). In 23 patients (79%) in group 1 scintigraphic findings were positive and in all 7 in group 2 they were negative. In 15 patients (52%) in group 1 and 1 patient (14%) in group 2, CK reached its peak level within 16 hours. In 20 patients (69%) in group 1 and 3 (43%) in group 2 the CK-MB level reached a peak within 16 hours. The sensitivity, specificity and predictive accuracy of positive results of early Tc-99m-PYP scintigraphy in predicting the reperfusion were 79%, 100% and 83%. These values are significantly higher than or similar to those of early peaking of CK and CK-MB release. In contrast to measurements of enzyme release, reperfusion data for Tc-99m-PYP scintigraphy are available immediately after thrombolytic therapy. Therefore, early Tc-99m-PYP scintigraphy (3 to 8 hours after onset of symptoms) is valuable as a noninvasive technique for early diagnosis of reperfusion.

  1. Transport time and care processes for patients transferred with ST-segment-elevation myocardial infarction: the reperfusion in acute myocardial infarction in Carolina emergency rooms experience.

    PubMed

    Muñoz, Daniel; Roettig, Mayme L; Monk, Lisa; Al-Khalidi, Hussein; Jollis, James G; Granger, Christopher B

    2012-08-01

    For patients with ST-segment elevation myocardial infarction transferred for primary percutaneous coronary intervention, guidelines have called for device activation within 90 minutes of initial presentation. Fewer than 20% of transferred patients are treated in such a timely fashion. We examine the association between transfer drive times and door-to-device (D2D) times in a network of North Carolina hospitals. We compare the feasibility of timely percutaneous coronary intervention using ground versus air transfer. We perform a retrospective analysis of the relationship between transfer drive times and D2D times in a 119-hospital ST-segment-elevation myocardial infarction statewide network. Between July 2008 and December 2009, 1537 ST-segment-elevation myocardial infarction patients underwent interhospital transfer for reperfusion via primary percutaneous coronary intervention. For ground transfers, median D2D time was 93 minutes for drive times ≤30 minutes, 117 minutes for drive times of 31 to 45 minutes, and 121 minutes for drive times >45 minutes. For air transfers, median D2D time was 125 minutes for drive times of 31 to 45 minutes and 138 minutes for drive times >45 minutes. Helicopter transport was associated with longer door-in door-out times and, ultimately, was associated with median D2D times that exceeded guideline recommendations, no matter the transfer drive time category. In a well-developed ST-segment-elevation myocardial infarction system, D2D times within 90 to 120 minutes appear most feasible for hospitals within 30-minute transfer drive time. Helicopter transport did not offer D2D time advantages for transferred STEMI patients. This finding appears to be attributable to comparably longer door-in door-out times for air transfers.

  2. Impact of Initial Culprit Vessel Flow on Infarct Size, Microvascular Obstruction, and Myocardial Salvage in Acute Reperfused ST-Elevation Myocardial Infarction.

    PubMed

    Joost, Alexander; Stiermaier, Thomas; Eitel, Charlotte; Fuernau, Georg; de Waha, Suzanne; Desch, Steffen; Thiele, Holger; Eitel, Ingo

    2016-11-01

    Data on the impact of initial Thrombolysis In Myocardial Infarction (TIMI) flow in the culprit coronary artery on myocardial damage after ST-elevation myocardial infarction (STEMI) are limited. Aim of this multicenter study was, therefore, to elucidate the impact of TIMI flow grade before percutaneous coronary intervention (PCI) on infarct size (IS), myocardial salvage index (MSI), and microvascular obstruction (MVO) assessed by cardiac magnetic resonance (CMR) imaging in patients with STEMI. We enrolled 738 patients with STEMI reperfused by primary PCI within 12 hours after symptom onset at 8 centers. Impaired coronary flow was defined as an initial coronary TIMI flow grade ≤1, whereas preserved coronary flow was defined as an initial coronary TIMI flow grade ≥2. CMR was performed in median 3 days (interquartile range 2 to 4 days) after infarction using a standardized infarction protocol. IS, MVO, and MSI were determined in central core laboratory-masked analyses. The primary clinical end point of the study was the time to major adverse cardiac events defined as death, reinfarction, and new onset of heart failure within 12 months after infarction. TIMI flow ≤1 before PCI was present in 507 patients (68.7%) and was significantly associated with larger IS (19% left ventricular [LV] vs 9% LV; p <0.001), less MSI (0.46 vs 0.65; p <0.001), reduced left ventricular ejection fraction (49% vs 55%; p <0.001), and a higher extent of MVO (0.6% LV vs 0.0% LV; p <0.001). Moreover, TIMI flow before PCI was identified as an independent predictor of IS, MVO, and MSI. However, there were no significant differences in major adverse cardiac event rates between groups (6.1% vs 7.5%; p = 0.48). In conclusion, TIMI flow pre-PCI is reversely associated with myocardial injury and is an independent predictor of myocardial damage assessed by CMR.

  3. [Myocardial ischemia-reperfusion injury and melatonin].

    PubMed

    Sahna, Engin; Deniz, Esra; Aksulu, Hakki Engin

    2006-06-01

    It is believed that myocardial ischemia-reperfusion injury is related to increased free radical generated and intracellular calcium overload especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger, antioxidant and can inhibit the intracellular calcium overload. In this review, we have summarized the fundamental of cardiac ischemia-reperfusion injury and the effects of melatonin on myocardial damage that related to cardiac ischemia-reperfusion injury. The total antioxidant capacity of human serum is related to melatonin levels. Incidence of sudden cardiac death is high in the morning hours. It has been shown that melatonin levels are significantly low at these times and patients with coronary heart disease have lower than normal individuals. These findings thought that melatonin would be valuable to test in clinical trials for prevention of possible ischemia-reperfusion-induced injury, especially life threatening arrhythmias and infarct size, effecting life quality, associated with thrombolysis, angioplasty, coronary artery spasm or coronary bypass surgery.

  4. Calpain system and its involvement in myocardial ischemia and reperfusion injury

    PubMed Central

    Neuhof, Christiane; Neuhof, Heinz

    2014-01-01

    Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria. Numerous experimental studies reveal an essential role of the calpain system in myocardial injury during ischemia, reperfusion and postischemic structural remodelling. The increasing Ca2+-content and Ca2+-overload in myocardial cytosol and mitochondria during ischemia and reperfusion causes an activation of calpains. Upon activation they are able to injure the contractile apparatus and impair the energy production by cleaving structural and functional proteins of myocytes and mitochondria. Besides their causal involvement in acute myocardial dysfunction they are also involved in structural remodelling after myocardial infarction by the generation and release of proapoptotic factors from mitochondria. Calpain inhibition can prevent or attenuate myocardial injury during ischemia, reperfusion, and in later stages of myocardial infarction. PMID:25068024

  5. The Effects of Oxygen Therapy on Myocardial Salvage in ST Elevation Myocardial Infarction Treated with Acute Percutaneous Coronary Intervention: The Supplemental Oxygen in Catheterized Coronary Emergency Reperfusion (SOCCER) Study.

    PubMed

    Khoshnood, Ardavan; Carlsson, Marcus; Akbarzadeh, Mahin; Bhiladvala, Pallonji; Roijer, Anders; Bodetoft, Stefan; Höglund, Peter; Zughaft, David; Todorova, Lizbet; Erlinge, David; Ekelund, Ulf

    2015-01-01

    Despite a lack of scientific evidence, oxygen has long been a part of standard treatment for patients with acute myocardial infarction (AMI). However, several studies suggest that oxygen therapy may have negative cardiovascular effects. We here describe a randomized controlled trial, i.e. Supplemental Oxygen in Catheterized Coronary Emergency Reperfusion (SOCCER), aiming to evaluate the effect of oxygen therapy on myocardial salvage and infarct size in patients with ST elevation myocardial infarction (STEMI) treated with a primary percutaneous coronary intervention (PCI). One hundred normoxic STEMI patients accepted for a primary PCI are randomized in the ambulance to either standard oxygen therapy or no supplemental oxygen. All patients undergo cardiovascular magnetic resonance imaging (CMR) 2-6 days after the primary PCI, and a subgroup of 50 patients undergo an extended echocardiography during admission and at 6 months. All patients are followed for 6 months for hospital admission for heart failure and subjective perception of health. The primary endpoint is the myocardial salvage index on CMR. Even though oxygen therapy is a part of standard care, oxygen may not be beneficial for patients with AMI and is possibly even harmful. The results of the present and concurrent oxygen trials may change international treatment guidelines for patients with AMI or ischemia.

  6. Lebetin 2, a Snake Venom-Derived Natriuretic Peptide, Attenuates Acute Myocardial Ischemic Injury through the Modulation of Mitochondrial Permeability Transition Pore at the Time of Reperfusion

    PubMed Central

    Tourki, Bochra; Matéo, Philippe; Morand, Jessica; Elayeb, Mohamed; Godin-Ribuot, Diane; Marrakchi, Naziha; Belaidi, Elise; Messadi, Erij

    2016-01-01

    Cardiac ischemia is one of the leading causes of death worldwide. It is now well established that natriuretic peptides can attenuate the development of irreversible ischemic injury during myocardial infarction. Lebetin 2 (L2) is a new discovered peptide isolated from Macrovipera lebetina venom with structural similarity to B-type natriuretic peptide (BNP). Our objectives were to define the acute cardioprotective actions of L2 in isolated Langendorff-perfused rat hearts after regional or global ischemia-reperfusion (IR). We studied infarct size, left ventricular contractile recovery, survival protein kinases and mitochondrial permeability transition pore (mPTP) opening in injured myocardium. L2 dosage was determined by preliminary experiments at its ability to induce cyclic guanosine monophosphate (cGMP) release without changing hemodynamic effects in normoxic hearts. L2 was found to be as effective as BNP in reducing infarct size after the induction of either regional or global IR. Both peptides equally improved contractile recovery after regional IR, but only L2 increased coronary flow and reduced severe contractile dysfunction after global ischemia. Cardioprotection afforded by L2 was abolished after isatin or 5-hydroxydecanote pretreatment suggesting the involvement of natriuretic peptide receptors and mitochondrial KATP (mitoKATP) channels in the L2-induced effects. L2 also increased survival protein expression in the reperfused myocardium as evidenced by phosphorylation of signaling pathways PKCε/ERK/GSK3β and PI3K/Akt/eNOS. IR induced mitochondrial pore opening, but this effect was markedly prevented by L2 treatment. These data show that L2 has strong cardioprotective effect in acute ischemia through stimulation of natriuretic peptide receptors. These beneficial effects are mediated, at least in part, by mitoKATP channel opening and downstream activated survival kinases, thus delaying mPTP opening and improving IR-induced mitochondrial dysfunction. PMID

  7. Protection against myocardial ischemia-reperfusion injury in clinical practice.

    PubMed

    Garcia-Dorado, David; Rodríguez-Sinovas, Antonio; Ruiz-Meana, Marisol; Inserte, Javier

    2014-05-01

    Even when reperfusion therapy is applied as early as possible, survival and quality of life are compromised in a considerable number of patients with ST-segment elevation acute myocardial infarction. Some cell death following transient coronary occlusion occurs during reperfusion, due to poor handling of calcium in the sarcoplasmic reticulum-mitochondria system, calpain activation, oxidative stress, and mitochondrial failure, all promoted by rapid normalization of intracellular pH. Various clinical trials have shown that infarct size can be limited by nonpharmacological strategies--such as ischemic postconditioning and remote ischemic conditioning--or by drugs--such as cyclosporine, insulin, glucagon-like peptide-1 agonists, beta-blockers, or stimulation of cyclic guanosine monophosphate synthesis. However, some clinical studies have yielded negative results, largely due to a lack of consistent preclinical data or a poor design, especially delayed administration. Large-scale clinical trials are therefore necessary, particularly those with primary clinical variables and combined therapies that consider age, sex, and comorbidities, to convert protection against reperfusion injury into a standard treatment for patients with ST-segment elevation acute myocardial infarction.

  8. Determinants of myocardial hemorrhage after coronary reperfusion in the anesthetized dog

    SciTech Connect

    Higginson, L.A.J.; White, F.; Heggtveit, H.A.; Sanders, T.M.; Bloor, C.M.; Covell, J.W.

    1982-01-01

    Intramyocardial hemorrhage often occurs with reperfusion in experimental acute myocardial infarction and is thought to be associated with extension of necrosis. To determine if hemorrhage was associated with extension of necrosis, 10 anesthetized dogs were reperfused after 6 hours of circumflex coronary artery occlusion and 10 others had control occlusion with no reperfusion. Fifteen of the 20 reperfused dogs had gross hemorrhage and none of the control dogs did. In 12 reperfused and 10 control dogs, radioactive microspheres were injected after coronary occlusion to quantitate collateral flow and in the reperfusion group microspheres were injected to quantitate reflow. Complete flow data were available in eight reperfused and 10 analyzed for hemorrhage, collateral flow and creatine kinase activity. Serial microscopic examination was performed in eight additional dogs reperfused after 6 hours to determine if hemorrhage occurs into otherwise microscopically normal myocardium. Pathologic examination indicatd that hemorrhage did not occur into otherwise microscopically normal myocardium. These studies indicate that hemorrhage or reperfusion is associated with severe myocardial necrosis and markedly depressed flow before reperfusion and this occurs only into myocardium already markedly compromised at the time of reperfusion.

  9. Core-shell hybrid liposomal vesicles loaded with panax notoginsenoside: preparation, characterization and protective effects on global cerebral ischemia/reperfusion injury and acute myocardial ischemia in rats

    PubMed Central

    Zhang, Jing; Han, Xizhen; Li, Xiang; Luo, Yun; Zhao, Haiping; Yang, Ming; Ni, Bin; Liao, Zhenggen

    2012-01-01

    Purpose: Novel panax notoginsenoside-loaded core-shell hybrid liposomal vesicles (PNS-HLV) were developed to resolve the restricted bioavailability of PNS and to enhance its protective effects in vivo on oral administration. Methods: Physicochemical characterizations of PNS-HLV included assessment of morphology, particle size and zeta potential, encapsulation efficiency (EE%), stability and in vitro release study. In addition, to evaluate its oral treatment potential, we compared the effect of PNS-HLV on global cerebral ischemia/reperfusion and acute myocardial ischemia injury with those of PNS solution, conventional PNS-loaded nanoparticles, and liposomes. Results: In comparison with PNS solution, conventional PNS-loaded nanoparticles and liposomes, PNS-HLV was stable for at least 12 months at 4°C. Satisfactory improvements in the EE% of notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were shown with the differences in EE% shortened and the greater controlled drug release profiles were exhibited from PNS-HLV. The improvements in the physicochemical properties of HLV contributed to the results that PNS-HLV was able to significantly inhibit the edema of brain and reduce the infarct volume, while it could markedly inhibit H2O2, modified Dixon agar, and serum lactate dehydrogenase, and increase superoxide dismutase (P < 0.05). Conclusion: The results of the present study imply that HLV has promising prospects for improving free drug bioactivity on oral administration. PMID:22915851

  10. CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury

    PubMed Central

    Weinreuter, Martin; Kreusser, Michael M; Beckendorf, Jan; Schreiter, Friederike C; Leuschner, Florian; Lehmann, Lorenz H; Hofmann, Kai P; Rostosky, Julia S; Diemert, Nathalie; Xu, Chang; Volz, Hans Christian; Jungmann, Andreas; Nickel, Alexander; Sticht, Carsten; Gretz, Norbert; Maack, Christoph; Schneider, Michael D; Gröne, Hermann-Josef; Müller, Oliver J; Katus, Hugo A; Backs, Johannes

    2014-01-01

    CaMKII was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. Here, we investigated the roles of different CaMKII isoforms and splice variants in ischemia/reperfusion (I/R) injury by the use of new genetic CaMKII mouse models. Although CaMKIIδC was upregulated 1 day after I/R injury, cardiac damage 1 day after I/R was neither affected in CaMKIIδ-deficient mice, CaMKIIδ-deficient mice in which the splice variants CaMKIIδB and C were re-expressed, nor in cardiomyocyte-specific CaMKIIδ/γ double knockout mice (DKO). In contrast, 5 weeks after I/R, DKO mice were protected against extensive scar formation and cardiac dysfunction, which was associated with reduced leukocyte infiltration and attenuated expression of members of the chemokine (C-C motif) ligand family, in particular CCL3 (macrophage inflammatory protein-1α, MIP-1α). Intriguingly, CaMKII was sufficient and required to induce CCL3 expression in isolated cardiomyocytes, indicating a cardiomyocyte autonomous effect. We propose that CaMKII-dependent chemoattractant signaling explains the effects on post-I/R remodeling. Taken together, we demonstrate that CaMKII is not critically involved in acute I/R-induced damage but in the process of post-infarct remodeling and inflammatory processes. PMID:25193973

  11. CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury.

    PubMed

    Weinreuter, Martin; Kreusser, Michael M; Beckendorf, Jan; Schreiter, Friederike C; Leuschner, Florian; Lehmann, Lorenz H; Hofmann, Kai P; Rostosky, Julia S; Diemert, Nathalie; Xu, Chang; Volz, Hans Christian; Jungmann, Andreas; Nickel, Alexander; Sticht, Carsten; Gretz, Norbert; Maack, Christoph; Schneider, Michael D; Gröne, Hermann-Josef; Müller, Oliver J; Katus, Hugo A; Backs, Johannes

    2014-10-01

    CaMKII was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. Here, we investigated the roles of different CaMKII isoforms and splice variants in ischemia/reperfusion (I/R) injury by the use of new genetic CaMKII mouse models. Although CaMKIIδC was upregulated 1 day after I/R injury, cardiac damage 1 day after I/R was neither affected in CaMKIIδ-deficient mice, CaMKIIδ-deficient mice in which the splice variants CaMKIIδB and C were re-expressed, nor in cardiomyocyte-specific CaMKIIδ/γ double knockout mice (DKO). In contrast, 5 weeks after I/R, DKO mice were protected against extensive scar formation and cardiac dysfunction, which was associated with reduced leukocyte infiltration and attenuated expression of members of the chemokine (C-C motif) ligand family, in particular CCL3 (macrophage inflammatory protein-1α, MIP-1α). Intriguingly, CaMKII was sufficient and required to induce CCL3 expression in isolated cardiomyocytes, indicating a cardiomyocyte autonomous effect. We propose that CaMKII-dependent chemoattractant signaling explains the effects on post-I/R remodeling. Taken together, we demonstrate that CaMKII is not critically involved in acute I/R-induced damage but in the process of post-infarct remodeling and inflammatory processes. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  12. Dissecting the Effects of Ischemia and Reperfusion on the Coronary Microcirculation in a Rat Model of Acute Myocardial Infarction

    PubMed Central

    Hollander, Maurits R.; de Waard, Guus A.; Konijnenberg, Lara S. F.; Meijer-van Putten, Rosalie M. E.; van den Brom, Charissa E.; Paauw, Nanne; de Vries, Helga E.; van de Ven, Peter M.; Aman, Jurjan; Van Nieuw-Amerongen, Geerten P.; Hordijk, Peter L.; Niessen, Hans W. M.; Horrevoets, Anton J. G.; Van Royen, Niels

    2016-01-01

    Background Microvascular injury (MVI) after coronary ischemia-reperfusion is associated with high morbidity and mortality. Both ischemia and reperfusion are involved in MVI, but to what degree these phases contribute is unknown. Understanding the etiology is essential for the development of new potential therapies. Methods and Findings Rats were divided into 3 groups receiving either 30 minutes ischemia, 90 minutes ischemia or 30 minutes ischemia followed by 60 minutes reperfusion. Subsequently hearts were ex-vivo perfused in a Langendorff-model. Fluorescence and electron microscopy was used for analysis of capillary density, vascular permeability and ultrastructure. Most MVI was observed after 30 minutes ischemia followed by 60 minutes reperfusion. In comparison to the 30’ and 90’ ischemia group, wall thickness decreased (207.0±74 vs 407.8±75 and 407.5±71, p = 0.02). Endothelial nuclei in the 30’-60’ group showed irreversible damage and decreased chromatin density variation (50.5±9.4, 35.4±7.1 and 23.7±3.8, p = 0.03). Cell junction density was lowest in the 30’-60’ group (0.15±0.02 vs 2.5±0.6 and 1.8±0.7, p<0.01). Microsphere extravasation was increased in both the 90’ ischemia and 30’-60’ group. Conclusions Ischemia alone for 90 minutes induces mild morphological changes to the coronary microcirculation, with increased vascular permeability. Ischemia for 30 minutes, followed by 60 minutes of reperfusion, induces massive MVI. This shows the direct consequences of reperfusion on the coronary microcirculation. These data imply that a therapeutic window exists to protect the microcirculation directly upon coronary revascularization. PMID:27391645

  13. The Comparison of the Outcomes between Primary PCI, Fibrinolysis, and No Reperfusion in Patients ≥ 75 Years Old with ST-Segment Elevation Myocardial Infarction: Results from the Chinese Acute Myocardial Infarction (CAMI) Registry

    PubMed Central

    Peiyuan, He; Jingang, Yang; Haiyan, Xu; Xiaojin, Gao; Ying, Xian; Yuan, Wu; Wei, Li; Yang, Wang; Xinran, Tang; Ruohua, Yan; Chen, Jin; Lei, Song; Xuan, Zhang; Rui, Fu; Yunqing, Ye; Qiuting, Dong; Hui, Sun; Xinxin, Yan; Runlin, Gao; Yuejin, Yang

    2016-01-01

    Background Only a few randomized trials have analyzed the clinical outcomes of elderly ST-segment elevation myocardial infarction (STEMI) patients (≥ 75 years old). Therefore, the best reperfusion strategy has not been well established. An observational study focused on clinical outcomes was performed in this population. Methods Based on the national registry on STEMI patients, the in-hospital outcomes of elderly patients with different reperfusion strategies were compared. The primary endpoint was defined as death. Secondary endpoints included recurrent myocardial infarction, ischemia driven revascularization, myocardial infarction related complications, and major bleeding. Multivariable regression analysis was performed to adjust for the baseline disparities between the groups. Results Patients who had primary percutaneous coronary intervention (PCI) or fibrinolysis were relatively younger. They came to hospital earlier, and had lower risk of death compared with patients who had no reperfusion. The guideline recommended medications were more frequently used in patients with primary PCI during the hospitalization and at discharge. The rates of death were 7.7%, 15.0%, and 19.9% respectively, with primary PCI, fibrinolysis, and no reperfusion (P < 0.001). Patients having primary PCI also had lower rates of heart failure, mechanical complications, and cardiac arrest compared with fibrinolysis and no reperfusion (P < 0.05). The rates of hemorrhage stroke (0.3%, 0.6%, and 0.1%) and other major bleeding (3.0%, 5.0%, and 3.1%) were similar in the primary PCI, fibrinolysis, and no reperfusion group (P > 0.05). In the multivariable regression analysis, primary PCI outweighs no reperfusion in predicting the in-hospital death in patients ≥ 75 years old. However, fibrinolysis does not. Conclusions Early reperfusion, especially primary PCI was safe and effective with absolute reduction of mortality compared with no reperfusion. However, certain randomized trials were

  14. Neuroprotective Antioxidant STAZN Protects Against Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Ley, James J.; Prado, Ricardo; Wei, Jian Qin; Bishopric, Nanette H.; Becker, David A.; Ginsberg, Myron D.

    2009-01-01

    Background Protecting the myocardium from ischemia-reperfusion injury has significant potential to reduce the complications of myocardial infarction and interventional revascularization procedures. Reperfusion damage is thought to result, in part, from oxidative stress. Here we use a novel method of percutaneous coronary occlusion to show that the potent antioxidant and neuroprotective free-radical scavenger, stilbazulenyl nitrone (STAZN), confers marked cardioprotection when given immediately prior to reperfusion. Methods and Results Physiologically controlled male Sprague-Dawley rats were anesthetized with isoflurane, paralyzed with pancuronium and mechanically ventilated. A guide wire was introduced via the femoral artery and advanced retrogradely via the aorta into the left coronary artery under fluoroscopic guidance. Rats with established coronary ischemia (85 min after occlusion) were given STAZN 3.5 mg/kg or its vehicle 5 minutes before and 2 hours after reperfusion, and were subjected to functional and histopathologic studies at 3 days. Ischemia-associated Q wave amplitude was reduced by 73% in STAZN-treated rats (P=0.01), while infarct-related ejection fraction, fractional shortening and severe regional wall-motion impairments were reduced by 48%, 54% and 37%, respectively, relative to vehicle-treated controls (P=0.05). Total myocardial infarct volume in STAZN-treated rats was correspondingly reduced by 43% (P<0.05), representing a sparing of 14% of the total left ventricular myocardium. Conclusions STAZN, a second-generation azulenyl nitrone with potent neuroprotective efficacy in brain ischemia, is also a rapidly acting and highly effective cardioprotective agent in acute coronary ischemia. Our results suggest the potential for clinical benefit in the setting of acute coronary syndromes. PMID:17936251

  15. Trends in acute reperfusion therapy for ST-segment elevation myocardial infarction from 1999 to 2006: we are getting better but we have got a long way to go.

    PubMed

    Eagle, Kim A; Nallamothu, Brahmajee K; Mehta, Rajendra H; Granger, Christopher B; Steg, Philippe Gabriel; Van de Werf, Frans; López-Sendón, Jose; Goodman, Shaun G; Quill, Ann; Fox, Keith A A

    2008-03-01

    Many patients who are eligible for acute reperfusion therapy receive it after substantial delays or not at all. We wanted to determine whether over the years more patients are receiving reperfusion therapy. This analysis is based on 10 954 patients with ST elevation or left bundle-branch block presenting within 12 h of symptom onset and enrolled in the GRACE registry between April 1999 and June 2006. Over this time, there was an increasing trend in use of primary percutaneous coronary intervention (PCI) from 15% to 44% (P < 0.001), while use of fibrinolytic therapy decreased (from 41 to 16%; P < 0.01). No trend in median time to primary PCI was seen but that for fibrinolysis declined significantly (from 40 to 34%; P < 0.0001). Hospital mortality declined (6.9-5.4%; P < 0.01); the relationship between observed and expected mortality improved over time (P = 0.06). Nevertheless, 33% of patients still received no reperfusion therapy. Factors associated with reperfusion use included age; prior myocardial infarction, heart failure or coronary artery bypass graft surgery; history of diabetes; female sex; and delay from symptom onset to hospital arrival. In 2006, 52% of patients receiving fibrinolysis had door-to-needle times >30 min and 42% of those undergoing primary PCI had door-to-balloon times >90 min. Primary PCI is now used much more than fibrinolysis. Although hospital mortality and delays to fibrinolytic reperfusion have improved, over 40% of patients reperfused still receive it outside the time window recommended, and one-third of potentially eligible patients receive no reperfusion.

  16. Cardiac remodeling following reperfused acute myocardial infarction is linked to the concomitant evolution of vascular function as assessed by cardiovascular magnetic resonance.

    PubMed

    Huttin, Olivier; Mandry, Damien; Eschalier, Romain; Zhang, Lin; Micard, Emilien; Odille, Freddy; Beaumont, Marine; Fay, Renaud; Felblinger, Jacques; Camenzind, Edoardo; Zannad, Faïez; Girerd, Nicolas; Marie, Pierre Y

    2017-01-04

    Left ventricular (LV) remodeling following acute myocardial infarction (MI) is difficult to predict at an individual level although a possible interfering role of vascular function has yet to be considered to date. This study aimed to determine the extent to which this LV remodeling is influenced by the concomitant evolution of vascular function and LV loading conditions, as assessed by phase-contrast Cardiovascular Magnetic Resonance (CMR) of the ascending aorta. CMR was performed in 121 patients, 2-4 days after reperfusion of a first ST-segment elevation myocardial infarction and 6 months thereafter. LV remodeling was: (i) assessed by the 6-month increase in end-diastolic volume (EDV) and/or ejection fraction (EF) and (ii) correlated with the indexed aortic stroke volume (mL.m(-2)), determined by a CMR phase-contrast sequence, along with derived functional vascular parameters (total peripheral vascular resistance (TPVR), total arterial compliance index, effective arterial elastance). At 6 months, most patients were under angiotensin enzyme converting inhibitors (86%) and beta-blockers (84%) and, on average, all functional vascular parameters were improved whereas blood pressure levels were not. An increase in EDV only (EDV+/EF-) was documented in 17% of patients at 6 months, in EF only (EDV-/EF+) in 31%, in both EDV and EF (EDV+/EF+) in 12% and neither EDV nor EF (EDV-/EF-) in 40%. The increase in EF was mainly and independently linked to a concomitant decline in TPVR (6-month change in mmHg.min.m(2).L(-1), EDV-/EF-: +1 ± 8, EDV+/EF-: +3 ± 9, EDV-/EF+: -7 ± 6, EDV+/EF+: -15 ± 20, p < 0.001) while the absence of any EF improvement was associated with high persisting rates of abnormally high TPVR at 6 months (EDV-/EF-: 31%, EDV+/EF-: 38%, EDV-/EF+: 5%, EDV+/EF+: 13%, p = 0.007). By contrast, the 6-month increase in EDV was mainly dependent on cardiac as opposed to vascular parameters and particularly on the presence of microvascular

  17. Cardiovascular magnetic resonance of the myocardium at risk in acute reperfused myocardial infarction: comparison of T2-weighted imaging versus the circumferential endocardial extent of late gadolinium enhancement with transmural projection.

    PubMed

    Ubachs, Joey F A; Engblom, Henrik; Erlinge, David; Jovinge, Stefan; Hedström, Erik; Carlsson, Marcus; Arheden, Håkan

    2010-03-29

    In the situation of acute coronary occlusion, the myocardium supplied by the occluded vessel is subject to ischemia and is referred to as the myocardium at risk (MaR). Single photon emission computed tomography has previously been used for quantitative assessment of the MaR. It is, however, associated with considerable logistic challenges for employment in clinical routine. Recently, T2-weighted cardiovascular magnetic resonance (CMR) has been introduced as a new method for assessing MaR several days after the acute event. Furthermore, it has been suggested that the endocardial extent of infarction as assessed by late gadolinium enhanced (LGE) CMR can also be used to quantify the MaR. Hence, we sought to assess the ability of endocardial extent of infarction by LGE CMR to predict MaR as compared to T2-weighted imaging. Thirty-seven patients with early reperfused first-time ST-segment elevation myocardial infarction underwent CMR imaging within the first week after percutaneous coronary intervention. The ability of endocardial extent of infarction by LGE CMR to assess MaR was evaluated using T2-weighted imaging as the reference method. MaR determined with T2-weighted imaging (34 +/- 10%) was significantly higher (p < 0.001) compared to the MaR determined with endocardial extent of infarction (23 +/- 12%). There was a weak correlation between the two methods (r2 = 0.17, p = 0.002) with a bias of -11 +/- 12%. Myocardial salvage determined with T2-weighted imaging (58 +/- 22%) was significantly higher (p < 0.001) compared to myocardial salvage determined with endocardial extent of infarction (45 +/- 23%). No MaR could be determined by endocardial extent of infarction in two patients with aborted myocardial infarction. This study demonstrated that the endocardial extent of infarction as assessed by LGE CMR underestimates MaR in comparison to T2-weighted imaging, especially in patients with early reperfusion and aborted myocardial infarction.

  18. Reduction of myocardial infarct size after ischemia and reperfusion by the glycosaminoglycan pentosan polysulfate.

    PubMed

    Tanhehco, E J; Kilgore, K S; Naylor, K B; Park, J L; Booth, E A; Lucchesi, B R

    1999-07-01

    Activation of the complement system contributes to the tissue destruction associated with myocardial ischemia/reperfusion. Pentosan polysulfate (PPS), a negatively charged sulfated glycosaminoglycan (GAG) and an effective inhibitor of complement activation, was studied for its potential to decrease infarct size in an experimental model of myocardial ischemia/reperfusion injury. Open-chest rabbits were subjected to 30-min occlusion of the left coronary artery followed by 5 h of reperfusion. Vehicle (saline) or PPS (30 mg/kg/h) was administered intravenously immediately before the onset of reperfusion and every hour during the reperfusion period. Treatment with PPS significantly (p < 0.05) reduced infarct size as compared with vehicle-treated animals (27.5+/-2.9% vs. 13.34+/-2.6%). Analysis of tissue demonstrated decreased deposition of membrane-attack complex and neutrophil accumulation in the area at risk. The results indicate that, like heparin and related GAGs, PPS possesses the ability to decrease infarct size after an acute period of myocardial ischemia and reperfusion. The observations are consistent with the suggestion that PPS may mediate its cytoprotective effect through modulation of the complement cascade.

  19. Leukocyte CD11a expression and granulocyte activation during experimental myocardial ischemia and long lasting reperfusion

    PubMed Central

    Lantos, János; Grama, László; Orosz, Tamás; Temes, Gyula; Rőth, Elizabeth

    2001-01-01

    BACKGROUND: Myocardial ischemia and reperfusion are accompanied by leukocyte activation and expression of surface adhesion molecules, which induce pathological interactions between endothelial cells and circulating neutrophils, leading to tissue damage. While the dynamics of these processes have been well defined during acute reperfusion, there is very little information regarding long lasting reperfusion. OBJECTIVES: To investigate neutrophil granulocyte (PMN) activation and the CD11a expression of leukocytes during myocardial ischemia and reperfusion for four weeks. ANIMALS AND METHODS: The left anterior descending coronary artery was occluded for 1 h in six dogs, followed by reperfusion for four weeks. Peripheral blood samples were collected before the operation, at the end of ischemia, at 5 and 60 min of reperfusion, and on postoperative days 1, 2, 3, 7, 14, 21 and 28. Sham operation on four dogs served as control. Leukocyte expression of CD11a was measured by flow cytometry. Superoxide radical production of isolated PMNs was determined spectrophotometrically. RESULTS: Granulocyte CD11a expression increased while the superoxide radical-producing capacity decreased significantly by the third postoperative day. Sham operation produced similar alterations in these parameters during the first postoperative week. From the second postoperative week, however, granulocyte radical production and adhesion molecule expression were higher in the ischemic animals. CONCLUSIONS: The exhaustion of PMN radical production and maximal CD11a expression during the first postoperative week are probably due to the surgical trauma caused by thoracotomy, but increased granulocyte function during later reperfusion indicates prolonged healing of injured myocardium. PMID:20428266

  20. Distinct effects of acute pretreatment with lipophilic and hydrophilic statins on myocardial stunning, arrhythmias and lethal injury in the rat heart subjected to ischemia/reperfusion.

    PubMed

    Čarnická, S; Adameová, A; Nemčeková, M; Matejíková, J; Pancza, D; Ravingerová, T

    2011-01-01

    Although both lipophilic and more hydrophilic statins share the same pathway of the inhibition of HMG-CoA reductase, their pleiotropic cardioprotective effects associated with the ability to cross cellular membranes, including membranes of heart cells, may differ. To test this hypothesis, isolated rat hearts were Langendorff-perfused either with simvastatin (S, 10 micromol/l) or pravastatin (P, 30 micromol/l), 15 min prior to ischemia. Control untreated hearts (C) were perfused with perfusion medium only. Postischemic contractile dysfunction, reperfusion-induced ventricular arrhythmias and infarct size were investigated after exposure of the hearts to 30-min global ischemia and 2-h reperfusion. Both lipophilic S and hydrophilic P reduced the severity of ventricular arrhythmias (arrhythmia score) from 4.3 +/- 0.2 in C to 3.0 +/- 0 and 2.7 +/- 0.2 in S and P, respectively, (both P < 0.05), decreased the duration of ventricular tachycardia and suppressed ventricular fibrillation. Likewise, the extent of lethal injury (infarct size) determined by tetrazolium staining and expressed in percentage of risk area, was significantly lower in both treated groups, moreover, the effect of P was more pronounced (27 +/- 2 % and 10 +/- 2 % in S and P groups, respectively, vs. 42 +/- 1 % in C; P < 0.05). In contrast, only S, but not P, was able to improve postischemic recovery of left ventricular developed pressure (LVDP; 48 +/- 12 % of preischemic values vs. 25 +/- 4 % in C and 21 +/ -7 % in P groups; P < 0.05). Our results suggest that differences in water solubility of statins indicating a different ability to cross cardiac membranes may underlie their distinct cardioprotective effects on myocardial stunning and lethal injury induced by ischemia/reperfusion.

  1. Demonstration of reperfusion after thrombolysis with technetium-99m isonitrile myocardial imaging

    SciTech Connect

    Kayden, D.S.; Mattera, J.A.; Zaret, B.L.; Wackers, F.J.

    1988-11-01

    Technetium-99m isonitrile myocardial perfusion imaging was employed in a patient undergoing thrombolytic therapy with recombinant tissue plasminogen activator for acute anteroseptal myocardial infarction. Technetium-99m isonitrile does not demonstrate significant myocardial redistribution after intravenous injection. The imaging agent was administered in the emergency room, prior to the initiation of thrombolytic therapy. The initial area at risk for infarction was visualized on images obtained after the patient had been effectively treated. Imaging performed 5 days later, after repeat injection of (99mTc)isonitrile, showed a smaller myocardial perfusion defect indicating salvage of myocardium. Thus, this technique offers promise as a noninvasive means of assessing the area at risk, the success of reperfusion, and the presence of salvaged myocardium, early in the course of acute myocardial infarction.

  2. Extracellular cyclophilin A may be a potential target to protect against myocardial reperfusion injury.

    PubMed

    Wang, W L; Yuan, Y J; Xue, F S; Liao, X; Wang, Q; Xiong, J; Liu, J H

    2011-11-01

    Myocardial reperfusion injury is increasingly recognized as an inflammatory process, characterized by neutrophil recruitment and subsequently excessive release of pro-inflammatory factors. Recently, the extracellular cyclophilin A (CypA) has been showed to play an important role in initiation and development of inflammation by chemo trafficking of leukocytes into inflamed tissues, eliciting massive release of pro-inflammatory cytokines, and inducing production of matrix metalloproteinases. Also, the agents targeting CypA have been demonstrated to promise anti-inflammatory effects in the different experimental models of inflammatory diseases including acute lung injury, rheumatoid arthritis, and atherosclerosis. Therefore, we hypothesize that the extracellular CypA may in some way implicated in the pathogenesis of reperfusion-induced inflammatory process, and the specific inhibitors of the extracellular CypA can provide a protection against the myocardial reperfusion injury. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Rat experimental model of myocardial ischemia/reperfusion injury: an ethical approach to set up the analgesic management of acute post-surgical pain.

    PubMed

    Ciuffreda, Maria Chiara; Tolva, Valerio; Casana, Renato; Gnecchi, Massimiliano; Vanoli, Emilio; Spazzolini, Carla; Roughan, John; Calvillo, Laura

    2014-01-01

    During the past 30 years, myocardial ischemia/reperfusion injury in rodents became one of the most commonly used model in cardiovascular research. Appropriate pain-prevention appears critical since it may influence the outcome and the results obtained with this model. However, there are no proper guidelines for pain management in rats undergoing thoracic surgery. Accordingly, we evaluated three analgesic regimens in cardiac ischemia/reperfusion injury. This study was strongly focused on 3R's ethic principles, in particular the principle of Reduction. Rats undergoing surgery were treated with pre-surgical tramadol (45 mg/kg intra-peritoneal), or carprofen (5 mg/kg sub-cutaneous), or with pre-surgical administration of carprofen followed by 2 post-surgery tramadol injections (multi-modal group). We assessed behavioral signs of pain and made a subjective evaluation of stress and suffering one and two hours after surgery. Multi-modal treatment significantly reduced the number of signs of pain compared to carprofen alone at both the first hour (61±42 vs 123±47; p<0.05) and the second hour (43±21 vs 74±24; p<0.05) post-surgery. Tramadol alone appeared as effective as multi-modal treatment during the first hour, but signs of pain significantly increased one hour later (from 66±72 to 151±86, p<0.05). Carprofen alone was more effective at the second hour post-surgery when signs of pain reduced to 74±24 from 113±40 in the first hour (p<0.05). Stress behaviors during the second hour were observed in only 20% of rats in the multimodal group compared to 75% and 86% in the carprofen and tramadol groups, respectively (p<0.05). Multi-modal treatment with carprofen and tramadol was more effective in preventing pain during the second hour after surgery compared with both tramadol or carprofen. Our results suggest that the combination of carprofen and tramadol represent the best therapy to prevent animal pain after myocardial ischemia/reperfusion. We obtained our results

  4. Rat Experimental Model of Myocardial Ischemia/Reperfusion Injury: An Ethical Approach to Set up the Analgesic Management of Acute Post-Surgical Pain

    PubMed Central

    Ciuffreda, Maria Chiara; Tolva, Valerio; Casana, Renato; Gnecchi, Massimiliano; Vanoli, Emilio; Spazzolini, Carla; Roughan, John; Calvillo, Laura

    2014-01-01

    Rationale During the past 30 years, myocardial ischemia/reperfusion injury in rodents became one of the most commonly used model in cardiovascular research. Appropriate pain-prevention appears critical since it may influence the outcome and the results obtained with this model. However, there are no proper guidelines for pain management in rats undergoing thoracic surgery. Accordingly, we evaluated three analgesic regimens in cardiac ischemia/reperfusion injury. This study was strongly focused on 3R’s ethic principles, in particular the principle of Reduction. Methods Rats undergoing surgery were treated with pre-surgical tramadol (45 mg/kg intra-peritoneal), or carprofen (5 mg/kg sub-cutaneous), or with pre-surgical administration of carprofen followed by 2 post-surgery tramadol injections (multi-modal group). We assessed behavioral signs of pain and made a subjective evaluation of stress and suffering one and two hours after surgery. Results Multi-modal treatment significantly reduced the number of signs of pain compared to carprofen alone at both the first hour (61±42 vs 123±47; p<0.05) and the second hour (43±21 vs 74±24; p<0.05) post-surgery. Tramadol alone appeared as effective as multi-modal treatment during the first hour, but signs of pain significantly increased one hour later (from 66±72 to 151±86, p<0.05). Carprofen alone was more effective at the second hour post-surgery when signs of pain reduced to 74±24 from 113±40 in the first hour (p<0.05). Stress behaviors during the second hour were observed in only 20% of rats in the multimodal group compared to 75% and 86% in the carprofen and tramadol groups, respectively (p<0.05). Conclusions Multi-modal treatment with carprofen and tramadol was more effective in preventing pain during the second hour after surgery compared with both tramadol or carprofen. Our results suggest that the combination of carprofen and tramadol represent the best therapy to prevent animal pain after myocardial ischemia/reperfusion

  5. The preventive effect of garlicin on a porcine model of myocardial infarction reperfusion no-reflow.

    PubMed

    Li, Jia-hui; Yang, Peng; Li, Ai-li; Wang, Yong; Shi, Zai-xiang; Ke, Yuan-nan; Li, Xian-lun

    2014-06-01

    To evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). Twenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA). Left ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group P<0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01). Garlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.

  6. Antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. against acute ischemia/reperfusion-induced myocardial injury in isolated rat heart.

    PubMed

    Jiang, Jiangtao; Yuan, Xuan; Wang, Ting; Chen, Hongmei; Zhao, Hong; Yan, Xinyan; Wang, Zhiping; Sun, Xiling; Zheng, Qiusheng

    2014-03-01

    This study evaluates antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. (DML). The total flavonoids showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide anion radicals in vitro. Compared with the ischemia/reperfusion (I/R) group as demonstrated by the use of improved Langendorff retrograde perfusion technology, the total flavonoids (5 μg/mL) pretreatment improved the heart rate and coronary flow, rised left ventricular developed pressure and decreased creatine kinase, lactate dehydrogenase levels in coronary flow. The infarct size/ischemic area at risk of DML-treated hearts was smaller than that of I/R group; the superoxide dismutase activity and glutathione/glutathione disulfide ratio increased and malondialdehyde content reduced obviously (P < 0.01) in total flavonoids treatment groups. In conclusion, the total flavonoids possess obvious protective effects on myocardial I/R injury, which may be related to the improvement of myocardial oxidative stress states.

  7. Effectiveness of Panax ginseng on Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway.

    PubMed

    Pei, Luo; Shaozhen, Hou; Gengting, Dong; Tingbo, Chen; Liang, Liu; Hua, Zhou

    2013-01-01

    Mechanisms for Panax ginseng's cardioprotective effect against ischemia reperfusion injury involve the estrogen-mediated pathway, but little is known about the role of androgen. A standardized Panax ginseng extract (RSE) was orally given with or without flutamide in a left anterior descending coronary artery ligation rat model. Infarct size, CK and LDH activities were measured. Time-related changes of NO, PI3K/Akt/eNOS signaling, and testosterone concentration were also investigated. RSE (80 mg/kg) significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE. NO was increased by RSE and reached a peak after 15 min of ischemia; however, flutamide cotreatment suppressed this elevation. Western blot analysis showed that RSE significantly reversed the decreases of expression and activation of PI3K, Akt, and eNOS evoked by ischemia, whereas flutamide attenuated the effects of these protective mechanisms induced by RSE. RSE completely reversed the dropping of endogenous testosterone level induced by I/R injury. Flutamide plus RSE treatment not only abolished RSE's effect but also produced a dramatic change on endogenous testosterone level after pretreatment and ischemia. Our results for the first time indicate that blocking androgen receptor abolishes the ability of Panax ginseng to protect the heart from myocardial I/R injury.

  8. Effectiveness of Panax ginseng on Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway

    PubMed Central

    Pei, Luo; Shaozhen, Hou; Gengting, Dong; Tingbo, Chen; Liang, Liu; Hua, Zhou

    2013-01-01

    Mechanisms for Panax ginseng's cardioprotective effect against ischemia reperfusion injury involve the estrogen-mediated pathway, but little is known about the role of androgen. A standardized Panax ginseng extract (RSE) was orally given with or without flutamide in a left anterior descending coronary artery ligation rat model. Infarct size, CK and LDH activities were measured. Time-related changes of NO, PI3K/Akt/eNOS signaling, and testosterone concentration were also investigated. RSE (80 mg/kg) significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE. NO was increased by RSE and reached a peak after 15 min of ischemia; however, flutamide cotreatment suppressed this elevation. Western blot analysis showed that RSE significantly reversed the decreases of expression and activation of PI3K, Akt, and eNOS evoked by ischemia, whereas flutamide attenuated the effects of these protective mechanisms induced by RSE. RSE completely reversed the dropping of endogenous testosterone level induced by I/R injury. Flutamide plus RSE treatment not only abolished RSE's effect but also produced a dramatic change on endogenous testosterone level after pretreatment and ischemia. Our results for the first time indicate that blocking androgen receptor abolishes the ability of Panax ginseng to protect the heart from myocardial I/R injury. PMID:24282438

  9. Cardiovascular magnetic resonance of the myocardium at risk in acute reperfused myocardial infarction: comparison of T2-weighted imaging versus the circumferential endocardial extent of late gadolinium enhancement with transmural projection

    PubMed Central

    2010-01-01

    Background In the situation of acute coronary occlusion, the myocardium supplied by the occluded vessel is subject to ischemia and is referred to as the myocardium at risk (MaR). Single photon emission computed tomography has previously been used for quantitative assessment of the MaR. It is, however, associated with considerable logistic challenges for employment in clinical routine. Recently, T2-weighted cardiovascular magnetic resonance (CMR) has been introduced as a new method for assessing MaR several days after the acute event. Furthermore, it has been suggested that the endocardial extent of infarction as assessed by late gadolinium enhanced (LGE) CMR can also be used to quantify the MaR. Hence, we sought to assess the ability of endocardial extent of infarction by LGE CMR to predict MaR as compared to T2-weighted imaging. Methods Thirty-seven patients with early reperfused first-time ST-segment elevation myocardial infarction underwent CMR imaging within the first week after percutaneous coronary intervention. The ability of endocardial extent of infarction by LGE CMR to assess MaR was evaluated using T2-weighted imaging as the reference method. Results MaR determined with T2-weighted imaging (34 ± 10%) was significantly higher (p < 0.001) compared to the MaR determined with endocardial extent of infarction (23 ± 12%). There was a weak correlation between the two methods (r2 = 0.17, p = 0.002) with a bias of -11 ± 12%. Myocardial salvage determined with T2-weighted imaging (58 ± 22%) was significantly higher (p < 0.001) compared to myocardial salvage determined with endocardial extent of infarction (45 ± 23%). No MaR could be determined by endocardial extent of infarction in two patients with aborted myocardial infarction. Conclusions This study demonstrated that the endocardial extent of infarction as assessed by LGE CMR underestimates MaR in comparison to T2-weighted imaging, especially in patients with early reperfusion and aborted myocardial

  10. Late reperfusion of a totally occluded infarct-related artery increases granulocyte-colony stimulation factor and reduces stroma-derived factor-1alpha blood levels in patients with ongoing ischemia after acute myocardial infarction.

    PubMed

    Kuo, Li-Tang; Chen, Shih-Jen; Cherng, Wen-Jin; Yang, Ning-I; Lee, Chen-Chin; Cheng, Chi-Wen; Verma, Subodh; Wang, Chao-Hung

    2009-07-01

    After acute myocardial infarction (AMI), reopening of a totally occluded infarct-related artery (IRA) at a subacute stage is still controversial in symptom-free patients. However, in patients with persistent ischemic symptoms and inadequate collaterals to the infarct area, recanalization is thought to provide beneficial effects. In addition to augmenting myocardial perfusion, we hypothesized that the benefit of recanalization involves the manipulation of circulating stem cell-mobilizing cytokines. This study included 30 patients with a totally occluded IRA and ongoing ischemic symptoms (the study group) and 30 patients with a partially occluded IRA (the control group). All patients underwent successful angioplasty and/or stenting. Before and immediately after the coronary intervention, blood granulocyte-colony-stimulating factor (G-CSF), stem-cell factor (SCF), vascular endothelial growth factor (VEGF), and stroma-derived factor-1 (SDF-1alpha) were measured. After recanalization, G-CSF levels significantly increased in the study group compared to the control group (P=0.03). SDF-1alpha levels in the study group decreased relative to the controls (P=0.02). However, no significant changes in VEGF or SCF levels between the two groups were found. In the multivariate analysis, reopening of a totally occluded IRA was independently and significantly associated with changes in G-CSF and SDF-1alpha levels after recanalization. In conclusion, our data suggest that the benefits of late reperfusion of a totally occluded IRA in patients with ongoing myocardial ischemia may involve mechanisms associated with stem cell-mobilizing and plaque-stabilizing cytokines. This study provides the rationale to investigate serial changes in cytokines and the numbers of circulating progenitors after reperfusion in the future.

  11. Role of myocardial perfusion imaging in evaluating thrombolytic therapy for acute myocardial infarction

    SciTech Connect

    Beller, G.A.

    1987-03-01

    Myocardial thallium-201 scintigraphy is being increasingly employed as a method for assessing the efficacy of coronary reperfusion in acute myocardial infarction. New thallium uptake after intracoronary tracer administration after successful recanalization indicates that nutrient blood flow has been successfully restored. One may also presume that some myocardial salvage occurred if thallium administered in this manner is transported intracellularly by myocytes with intact sarcolemmal membranes. However, if one injects thallium by way of the intracoronary route immediately after reperfusion, the initial uptake of thallium in reperfused myocardium may predominantly represent hyperemic flow and regional thallium counts measured may not be proportional to the mass of viable myocytes. When thallium is injected intravenously during the occlusion phase the degree of redistribution after thrombolysis is proportional to the degree of flow restoration and myocardial viability. When thallium is injected for the first time intravenously immediately after reperfusion, an overestimation of myocardial salvage may occur because of excess thallium uptake in the infarct zone consequent to significant hyperemia. Another approach to myocardial thallium scintigraphy in patients undergoing thrombolytic therapy is to administer two separate intravenous injections before and 24 hours or later after treatment. Finally, patients with acute myocardial infarction who receive intravenous thrombolytic therapy are candidates for predischarge exercise thallium-201 scintigraphy for risk stratification and detection of residual ischemia.

  12. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II).

    PubMed

    Ross, Allan M; Gibbons, Raymond J; Stone, Gregg W; Kloner, Robert A; Alexander, R Wayne

    2005-06-07

    The purpose of this research was to determine the effect of intravenous adenosine on clinical outcomes and infarct size in ST-segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy. Previous small studies suggest that adenosine may reduce the size of an evolving infarction. Patients (n = 2,118) with evolving anterior STEMI receiving thrombolysis or primary angioplasty were randomized to a 3-h infusion of either adenosine 50 or 70 microg/kg/min or of placebo. The primary end point was new congestive heart failure (CHF) beginning >24 h after randomization, or the first re-hospitalization for CHF, or death from any cause within six months. Infarct size was measured in a subset of 243 patients by technetium-99m sestamibi tomography. There was no difference in the primary end point between placebo (17.9%) and either the pooled adenosine dose groups (16.3%) or, separately, the 50-microg/kg/min dose and 70-microg/kg/min groups (16.5% vs. 16.1%, respectively, p = 0.43). The pooled adenosine group trended toward a smaller median infarct size compared with the placebo group, 17% versus 27% (p = 0.074). A dose-response relationship with final median infarct size was seen: 11% at the high dose (p = 0.023 vs. placebo) and 23% at the low dose (p = NS vs. placebo). Infarct size and occurrence of a primary end point were significantly related (p < 0.001). Clinical outcomes in patients with STEMI undergoing reperfusion therapy were not significantly improved with adenosine, although infarct size was reduced with the 70-microg/kg/min adenosine infusion, a finding that correlated with fewer adverse clinical events. A larger study limited to the 70-microg/kg/min dose is, therefore, warranted.

  13. Reperfusion Therapy with Rapamycin Attenuates Myocardial Infarction through Activation of AKT and ERK

    PubMed Central

    Filippone, Scott M.; Samidurai, Arun; Roh, Sean K.; Cain, Chad K.; He, Jun; Salloum, Fadi N.; Kukreja, Rakesh C.

    2017-01-01

    Prompt coronary reperfusion is the gold standard for minimizing injury following acute myocardial infarction. Rapamycin, mammalian target of Rapamycin (mTOR) inhibitor, exerts preconditioning-like cardioprotective effects against ischemia/reperfusion (I/R) injury. We hypothesized that Rapamycin, given at the onset of reperfusion, reduces myocardial infarct size through modulation of mTOR complexes. Adult C57 male mice were subjected to 30 min of myocardial ischemia followed by reperfusion for 1 hour/24 hours. Rapamycin (0.25 mg/kg) or DMSO (7.5%) was injected intracardially at the onset of reperfusion. Post-I/R survival (87%) and cardiac function (fractional shortening, FS: 28.63 ± 3.01%) were improved in Rapamycin-treated mice compared to DMSO (survival: 63%, FS: 17.4 ± 2.6%). Rapamycin caused significant reduction in myocardial infarct size (IS: 26.2 ± 2.2%) and apoptosis (2.87 ± 0.64%) as compared to DMSO-treated mice (IS: 47.0 ± 2.3%; apoptosis: 7.39 ± 0.81%). Rapamycin induced phosphorylation of AKT S473 (target of mTORC2) but abolished ribosomal protein S6 phosphorylation (target of mTORC1) after I/R. Rapamycin induced phosphorylation of ERK1/2 but inhibited p38 phosphorylation. Infarct-limiting effect of Rapamycin was abolished with ERK inhibitor, PD98059. Rapamycin also attenuated Bax and increased Bcl-2/Bax ratio. These results suggest that reperfusion therapy with Rapamycin protects the heart against I/R injury by selective activation of mTORC2 and ERK with concurrent inhibition of mTORC1 and p38. PMID:28373901

  14. Cell therapy in reperfused acute myocardial infarction does not improve the recovery of perfusion in the infarcted myocardium: a cardiac MR imaging study.

    PubMed

    Robbers, Lourens F H J; Nijveldt, Robin; Beek, Aernout M; Hirsch, Alexander; van der Laan, Anja M; Delewi, Ronak; van der Vleuten, Pieter A; Tio, René A; Tijssen, Jan G P; Hofman, Mark B M; Piek, Jan J; Zijlstra, Felix; van Rossum, Albert C

    2014-07-01

    To investigate the effects of cell therapy on myocardial perfusion recovery after treatment of acute myocardial infarction (MI) with primary percutaneous coronary intervention (PCI). In this HEBE trial substudy, which was approved by the institutional review board (trial registry number ISRCTN95796863), the authors assessed the effects of intracoronary infusion with bone marrow-derived mononuclear cells (BMMCs) or peripheral blood-derived mononuclear cells (PBMCs) on myocardial perfusion recovery by using cardiac magnetic resonance (MR) imaging after revascularization. In 152 patients with acute MI treated with PCI, cardiac MR imaging was performed after obtaining informed consent-before randomization to BMMC, PBMC, or standard therapy (control group)-and repeated at 4-month follow-up. Cardiac MR imaging consisted of cine, rest first-pass perfusion, and late gadolinium enhancement imaging. Perfusion was evaluated semiquantitatively with signal intensity-time curves by calculating the relative upslope (percentage signal intensity change). The relative upslope was calculated for the MI core, adjacent border zone, and remote myocardium. Perfusion differences among treatment groups or between baseline and follow-up were assessed with the Wilcoxon signed rank or Mann-Whitney U test. At baseline, myocardial perfusion differed between the MI core (median, 6.0%; interquartile range [IQR], 4.1%-8.0%), border zone (median, 8.4%; IQR, 6.4%-10.2%), and remote myocardium (median, 12.2%; IQR, 10.5%-15.9%) (P < .001 for all), with equal distribution among treatment groups. These interregional differences persisted at follow-up (P < .001 for all). No difference in perfusion recovery was found between the three treatment groups for any region. After revascularization of ST-elevation MI, cell therapy does not augment the recovery of resting perfusion in either the MI core or border zone. © RSNA, 2014.

  15. Predictors of ventricular fibrillation at reperfusion in patients with acute ST-elevation myocardial infarction treated by primary percutaneous coronary intervention.

    PubMed

    Demidova, Marina M; Carlson, Jonas; Erlinge, David; Platonov, Pyotr G

    2015-02-15

    Ventricular fibrillation (VF) during reperfusion (rVF) in ST-segment elevation myocardial infarction (STEMI) is an infrequent but serious event that complicates coronary interventions. The aim of this study was to analyze clinical predictors of rVF in an unselected population of patients with STEMI treated with percutaneous coronary intervention (PCI). Consecutive patients with STEMI admitted to a tertiary care hospital for primary PCI from 2007 to 2012 were retrospectively assessed for the presence of rVF. Admission electrocardiograms, stored in a digital format, were analyzed for a maximal ST-segment elevation in a single lead and the sum of ST-segment deviations in all leads. Clinical, electrocardiographic, and angiographic characteristics were tested for associations with rVF using logistic regression analysis. Among 3,724 patients with STEMI admitted from 2007 to 2012, 71 (1.9%) had rVF. In univariate analysis, history of myocardial infarction, aspirin and β-blocker use, VF before PCI, left main coronary artery disease, inferior myocardial infarction localization, symptom-to-balloon time <360 minutes, maximal ST-segment elevation in a single lead >300 μV, and sum of ST-segment deviations in all leads >1,500 μV were associated with increased risk for rVF. In a multivariate analysis, sum of ST-segment deviations in all leads >1500 μV (odds ratio 3.7, 95% confidence interval 1.45 to 9.41, p = 0.006) before PCI remained an independent predictor of rVF. In-hospital mortality was 18.3% in the rVF group and 3.3% in the group without VF (p <0.001), but rVF was not an independent predictor of in-hospital death. In conclusion, the magnitude of ST-segment elevation before PCI for STEMI independently predicts rVF and should be considered in periprocedural arrhythmic risk assessment. Despite higher in-hospital mortality in patients with rVF, rVF itself has no independent prognostic value for prognosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. ST-segment resolution 60 minutes after combination treatment of abciximab with reteplase or reteplase alone for acute myocardial infarction (30-day mortality results from the resolution of ST-segment after reperfusion therapy substudy).

    PubMed

    Cura, Fernando A; Roffi, Marco; Pasca, Narcis; Wolski, Katherine E; Lincoff, A Michael; Topol, Eric J; Lauer, Michael S

    2004-10-01

    The combination of abciximab with thrombolytic therapy when treating acute ST-elevation myocardial infarction has been hypothesized to enhance microvascular perfusion. Resolution of ST-segment elevation after thrombolytic therapy is believed to be a marker of myocardial reperfusion and to predict mortality rate. Among 16,588 patients enrolled in the Fifth Global Use of Strategies to Open Occluded Arteries in Acute Myocardial Infarction trial, 1,764 consecutive patients from selected centers had their study electrocardiograms evaluated by a core laboratory for ST-segment deviation resolution 60 minutes after treatment. Patients were categorized into 4 groups: complete resolution (>70%), partial resolution (<70% to 30%), no resolution (<30%), and worsening ST-segment deviation. Patients treated with reteplase or a combination of reteplase plus abciximab had similar rates of complete resolution (32% vs 34%), partial resolution (29% vs 27%), no resolution (15% vs 16%), and worsening ST-segment elevation (23 vs 23%; p = 0.59). The 30-day mortality rates in these 4 groups were 2.1%, 5.2%, 5.5%, and 8.1% (p <0.001). Even after accounting for baseline variables, incomplete ST-segment resolution (<70%) was associated with an increased risk of death within 30 days (adjusted hazard ratio 2.41, 95% confidence interval 1.25 to 4.63, p <0.008). Thus, ST-segment resolution at 60 minutes was no different in patients treated with full-dose reteplase from those treated with a combination of abciximab and reteplase. Patients with >70% ST-segment resolution within 60 minutes had markedly decreased mortality rates, irrespective of treatment.

  17. Ginseng protects rodent hearts from acute myocardial ischemia-reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism.

    PubMed

    Zhou, Hua; Hou, Shao Zhen; Luo, Pei; Zeng, Bao; Wang, Jing Rong; Wong, Yuen Fan; Jiang, Zhi Hong; Liu, Liang

    2011-05-17

    Ginseng (Panax ginseng C.A. Meyer) is widely used in Asian communities for treating cardiovascular diseases. However, the mechanism by which it protects the myocardium in ischemia-reperfusion (I/R) injury remains unclear. In this study, we aim to investigate whether a standardized ginseng extract (RSE) protects rodent hearts against I/R injury and if glucocorticoid and/or estrogen receptor-mediated activation of Akt and Erk1/2 (the reperfusion injury salvage kinase pathway, RISK) and subsequent nitric oxide (NO) synthesis signaling are involved in this effect. Rats or gene-deleted mice were subjected to 30 min ischemia by occluding the left anterior descending coronary artery and 90 min reperfusion. Infarct size, serum level of creatine kinase (CK), lactate dehydrogenase (LDH), and NO, expression and phosphorylation of glucocorticoid receptor (GR), estrogen receptor (ER), phosphatidylinositol-3 kinase (PI3K), Akt, NO synthase (NOS), extracellular signal-regulated kinase (Erk) 1/2, p38, and c-Jun NH2 terminal kinases (JNK) were examined in rat or mice treated with or without RSE in the absence or presence of pharmacological inhibitors. RSE significantly reduced infarct size in a dose-dependent manner and reduced the incidence of arrhythmia, increased serum NO production, reduced serum activities of creatine kinase and lactate dehydrogenase. The infarct size reduction effect of RSE was abolished by RU468 (an inhibitor of GR), tamoxifen (an inhibitor of ER), LY294002 (an inhibitor of PI3K), Akt inhibitor IV (an inhibitor of Akt protein kinase), U0126 (an inhibitor of Erk1/2) and NG-nitro-l-arginine methyl ester hydrochloride (an inhibitor of NOS), but not actinomycin D (an inhibitor of transcription process). RSE also significantly increased the activation of GR/ER, PI3K-Akt-eNOS cascades and Erk1/2 signaling in rat heart. However, RSE did not markedly reduce infarct size in endothelium NOS(-/-) mice. This differs from its effect in inducible NOS(-/-) and wild type

  18. Iloprost reduces myocardial edema in a rat model of myocardial ischemia reperfusion.

    PubMed

    Caliskan, A; Yavuz, C; Karahan, O; Yazici, S; Guclu, O; Demirtas, S; Mavitas, B

    2014-05-01

    Myocardial ischemia severely reduces myocyte longevity and function. Extensive interstitial edema and cell damage occur as a result of myocardial reperfusion injury. Current therapies are directed at prevention of ischemia-induced damage to cardiac tissue. Iloprost is a novel pharmaceutical agent for the treatment of ischemia. Twenty rats were segregated into four experimental groups. The procedure control group consisted of four rats undergoing a sham operation. The remaining 16 rats were divided into two equal groups. The first group (control group) received a continuous intravenous infusion of physiological serum immediately prior to the procedure. Iloprost was administered by a continuous intravenous infusion into the right jugular vein at an infusion rate of 100 ng/kg/min for 30 minutes prior to reperfusion in the experimental group (study group). Following the infusion treatments, ligation of the left coronary artery was conducted for 30 minutes to induce myocardial ischemia. The rats were euthanized 24 hours after reperfusion and cardiac tissue was harvested from all specimens for analysis. Histological examination revealed three myocardial tissue specimens with grade II damage and five myocardial tissue specimens with grade III reperfusion injury in the control group. However, the study group consisted of two grade III myocardial tissue specimens, five grade II myocardial tissue specimens and one grade I myocardial tissue specimen. Moreover, a statistically significant reduction in myocardial edema was observed in the study group (p=0.022). Our results support the hypothesis that iloprost enhances protection against cardiac ischemia reperfusion injury. This protective effect may be associated with vasodilation, antioxidant or anti-edema mechanisms.

  19. Exogenous NAD+ administration significantly protects against myocardial ischemia/reperfusion injury in rat model

    PubMed Central

    Zhang, Youjun; Wang, Ban; Fu, Xingli; Guan, Shaofeng; Han, Wenzheng; Zhang, Jie; Gan, Qian; Fang, Weiyi; Ying, Weihai; Qu, Xinkai

    2016-01-01

    Acute myocardial infarction is one of the leading causes for death around the world. Although essential for successful interventional therapy, it is inevitably complicated by reperfusion injury. Thus effective approaches to reduce ischemia/reperfusion (I/R) injury are still critically needed. To test our hypothesis that intravenous administration of NAD+ can attenuate I/R injury by reducing apoptotic damage and enhancing antioxidant capacity, we used a rat mode of myocardial I/R. Our study found that administration of 10-20 mg/kg NAD+ can dose dependently reduce myocardial infarct induced by I/R, with an approximately 85% reduction of the infarct at the dosage of 20 mg/kg NAD+. We further found that the injection of NAD+ can significantly decrease I/R-induced apoptotic damage in the heart: NAD+ administration can both decrease the TUNEL signals, Bax, cleaved caspase-3 levels and increase the Bcl-XL levels in the rats that are subjected to myocardial I/R injury. NAD+ administration can also significantly attenuate I/R-induced decreases in SOD activity and SOD-2 protein levels in the hearts. NAD+ can profoundly decrease myocardial I/R injury at least partially by attenuating apoptotic damage and enhancing the antioxidant capacity, thus suggesting that NAD+ may become a promising therapeutic agent for myocardial I/R injury. PMID:27648125

  20. Purkinje fibers after myocardial ischemia-reperfusion.

    PubMed

    García Gómez-Heras, Soledad; Álvarez-Ayuso, Lourdes; Torralba Arranz, Amalia; Fernández-García, Héctor

    2015-07-01

    The purpose of this study was to evaluate the effects of ischemia-reperfusion on Purkinje fibers, comparing them with the adjacent cardiomyocytes. In a model of heterotopic heart transplantation in pigs, the donor heart was subjected to 2 hours of ischemia (n=9), preserved in cold saline, and subjected to 24 hours of ischemia with preservation in Wisconsin solution, alone (n=6), or with an additive consisting of calcium (n=4), Nicorandil (n=6) or Trolox (n=7). After 2 hours of reperfusion, we evaluated the recovery of cardiac electrical activity and took samples of ventricular myocardium for morphological study. The prolonged ischemia significantly affected atrial automaticity and A-V conduction in all the groups subjected to 24 hours of ischemia, as compared to 2 hours. There were no significant differences among the groups that underwent prolonged ischemia. Changes in the electrical activity did not correlate with the morphological changes. In the Purkinje fibers, ischemia-reperfusion produced a marked decrease in the glycogen content in all the groups. In the gap junctions the immunolabeling of connexin-43 decreased significantly, adopting a dispersed distribution, and staining the sarcolemma adjacent to the connective tissue. These changes were less marked in the group preserved exclusively with Wisconsin solution, despite the prolonged ischemia. The addition of other substances did not improve the altered morphology. In all the groups, the injury appeared to be more prominent in the Purkinje fibers than in the neighboring cardiomyocytes, indicating the greater susceptibility of the former to ischemia-reperfusion injury.

  1. Arginase as a target for treatment of myocardial ischemia-reperfusion injury.

    PubMed

    Tratsiakovich, Yahor; Yang, Jiangning; Gonon, Adrian Thomas; Sjöquist, Per-Ove; Pernow, John

    2013-11-15

    Two distinct enzymes of arginase (1 and 2) are critically regulating nitric oxide (NO) bioavailability by competing with NO synthase for their common substrate l-arginine. Increased expression and activity of arginase is observed in atherosclerosis and myocardial ischemia-reperfusion (I/R). Several studies have demonstrated a key pathophysiological role of increased activity of arginase during I/R. Pharmacological inhibition of arginase results in restoration of NO availability and salvage of myocardium during I/R. Arginase inhibition might be a promising therapeutic strategy for the limitation of myocardial injury in acute myocardial infarction. Current understanding of the role of arginase and efficacy of arginase inhibition during myocardial I/R is reviewed in the present article.

  2. Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction.

    PubMed

    Ekeløf, Sarah V; Halladin, Natalie L; Jensen, Svend E; Zaremba, Tomas; Aarøe, Jens; Kjærgaard, Benedict; Simonsen, Carsten W; Rosenberg, Jacob; Gögenur, Ismail

    2016-01-01

    Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma levels of high-sensitive troponin T were assessed repeatedly. The experimenters were blinded with regard to treatment regimen. Melatonin did not significantly increase myocardial salvage index compared with placebo [melatonin 21.8% (16.1; 24.8) vs. placebo 20.2% (16.9; 27.0), p = 1.00]. The extent of microvascular obstruction was similar between the groups [melatonin 3.8% (2.7; 7.1) vs. placebo 3.7% (1.3; 7.7), p = 0.96]. The area under the curve for high-sensitive troponin T release was insignificantly reduced by 32% in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4) ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.

  3. [The role of free radicals in the myocardial reperfusion injuries and in the development of endogenous adaptation].

    PubMed

    Rőth, Erzsébet

    2015-11-22

    The reperfusion of acute ischaemic myocardium is essential for myocardial salvage, so-called "gold standard" therapy, however it can result in serious damage to the myocardium. Functional alterations occur, including depressed contractile function and decreased coronary flow as well as altered vascular reactivity. Over several decades it has been demonstrated that oxygen radical formation is greatly increased in the post-ischaemic heart and serves as a critical central mechanism of ischaemic-reperfusion injury. However it has been demonstrated that free radicals play an important role in the endogenous adaptation phenomenon of the heart, too. Ischaemic preconditioning is a cellular adaptive response of the heart to stress, which provides the most potent endogenous protection against reperfusion arrhytmias, stunning and infarction. Post-conditioning defined as brief periods of ischaemia and reperfusion during the very early minutes of reperfusion stimulates endogenous adaptation. Post-conditioning may also attenuate the damage to endothelial cells and cardiomyocytes from oxidants, cytokines, proteases and inflammatory cells.

  4. Delayed coronary reperfusion is ineffective at impeding the dynamic increase in cardiac efferent sympathetic nerve activity following myocardial ischemia.

    PubMed

    Hall, Timothy M; Gordon, Christina; Roy, Ranjan; Schwenke, Daryl O

    2016-05-01

    Acute myocardial infarction (MI) is associated with an adverse and sustained increase in cardiac sympathetic nerve activity (SNA), triggering potentially fatal ventricular arrhythmias. While myocardial reperfusion undoubtedly improves patient prognosis, it remains unknown whether reperfusion therapy also attenuates the dangerous increase in SNA. This study aimed to investigate the effect of time-dependent coronary reperfusion therapy on cardiac SNA following acute MI. Electrophysiological recordings of cardiac efferent SNA were performed in urethane-anaesthetized rats following ligation of the left anterior descending coronary artery (i.e., MI) for either 15 or 45 min, followed by 'early' or 'delayed' reperfusion, respectively. Another group of rats had permanent ischemia with no reperfusion. Forty-five minutes of ischemia induced a 55 % increase in efferent SNA. Subsequent 'delayed' reperfusion was ineffective at ameliorating further increases in SNA (maximal 153 % increase), so that MI-induced increases in SNA mirrored that observed in rats with permanent MI. Although SNA did not increase during 15 min of ischemia, it did significantly increase, albeit delayed, during the subsequent reperfusion period (max. 75 % increase). Importantly, however, this increase in SNA, which tended to be lower in the 'early'-reperfusion group, was matched with a lower incidence of arrhythmias and mortality rate, compared to the 'delayed'-reperfusion and permanent-MI groups. These results highlight that 'prompt' coronary reperfusion, before SNA becomes activated, may provide a crucial window of opportunity for improving outcome. Further research is essential to identify the mechanisms that underpin, not only sympathetic activation, but also importantly sympathetic deactivation as a potential therapeutic target for MI.

  5. Myocardial ischemia/reperfusion impairs neurogenesis and hippocampal-dependent learning and memory.

    PubMed

    Evonuk, Kirsten S; Prabhu, Sumanth D; Young, Martin E; DeSilva, Tara M

    2017-03-01

    The incidence of cognitive impairment in cardiovascular disease (CVD) patients has increased, adversely impacting quality of life and imposing a significant economic burden. Brain imaging of CVD patients has detected changes in the hippocampus, a brain region critical for normal learning and memory. However, it is not clear whether adverse cardiac events or other associated co-morbidities impair cognition. Here, using a murine model of acute myocardial ischemia/reperfusion (I/R), where the coronary artery was occluded for 30min followed by reperfusion, we tested the hypothesis that acute myocardial infarction triggers impairment in cognitive function. Two months following cardiac I/R, behavioral assessments specific for hippocampal cognitive function were performed. Mice subjected to cardiac I/R performed worse in the fear-conditioning paradigm as well as the object location memory behavioral test compared to sham-operated mice. Reactive gliosis was apparent in the hippocampal subregions CA1, CA3, and dentate gyrus 72h post-cardiac I/R as compared with sham, which was sustained two months post-cardiac I/R. Consistent with the inflammatory response, the abundance of doublecortin positive newborn neurons was decreased in the dentate gyrus 72h and 2months post-cardiac I/R as compared with sham. Therefore, we conclude that following acute myocardial infarction, rapid inflammatory responses negatively affect neurogenesis, which may underlie long-term changes in learning and memory.

  6. Ipratropium bromide-mediated myocardial injury in in vitro models of myocardial ischaemia/reperfusion.

    PubMed

    Harvey, Kate L; Hussain, Afthab; Maddock, Helen L

    2014-04-01

    Ipratropium bromide, a nonselective muscarinic antagonist, is widely prescribed for the treatment of chronic obstructive pulmonary disease (COPD). Analyses of COPD patients, with underlying ischaemic heart disease, receiving anticholinergics, have indicated increased risk of severity and occurrence of cardiovascular events (including myocardial infarction). The present study explored whether ipratropium bromide induces myocardial injury in nonclinical models of simulated myocardial ischaemia/reperfusion injury. Adult Sprague Dawley rat hearts/primary ventricular myocytes were exposed to simulated ischaemia/hypoxia prior to administration of ipratropium at the onset of reperfusion/reoxygenation. Infarct to risk ratio and cell viability was measured via triphenyl tetrazolium chloride staining and thiazolyl blue tetrazolium bromide (MTT) assay. The involvement of apoptosis and necrosis was evaluated by flow cytometry. Mitochondrial-associated responses were detected by tetramethylrhodamine methyl ester fluorescence and myocyte contracture. Ipratropium (1 × 10⁻¹¹ M - 1 × 10⁻⁴ M) significantly increased infarct/risk ratio and decreased cell viability in a dose-dependent manner. Increased levels of necrosis and apoptosis were observed via flow cytometry, accompanied by increased levels of cleaved caspase-3 following ipratropium treatment. Levels of endogenous myocardial acetylcholine were verified via use of an acetylcholine assay. In these experimental models, exogenous acetylcholine (1 × 10⁻⁷ M) showed protective properties, when administered alone, as well as abrogating the exacerbation of myocardial injury during ischaemia/reperfusion following ipratropium coadministration. In parallel experiments, under conditions of myocardial ischaemia/reperfusion, a similar injury was observed following atropine (1 × 10⁻⁷ M) administration. These data demonstrate for the first time in a nonclinical setting that ipratropium exacerbates ischaemia/reperfusion

  7. Activation of Poly(ADP-Ribose) Polymerase by Myocardial Ischemia and Coronary Reperfusion in Human Circulating Leukocytes

    PubMed Central

    Tóth-Zsámboki, Emese; Horváth, Eszter; Vargova, Katarina; Pankotai, Eszter; Murthy, Kanneganti; Zsengellér, Zsuzsanna; Bárány, Tamás; Pék, Tamás; Fekete, Katalin; Kiss, Róbert Gábor; Préda, István; Lacza, Zsombor; Gerö, Domokos; Szabó, Csaba

    2006-01-01

    Reactive free radical and oxidant production leads to DNA damage during myocardial ischemia/reperfusion. Consequent overactivation of poly(ADP-ribose) polymerase (PARP) promotes cellular energy deficit and necrosis. We hypothesized that PARP is activated in circulating leukocytes in patients with myocardial infarction and reperfusion during primary percutaneous coronary intervention (PCI). In 15 patients with ST segment elevation acute myocardial infarction, before and after primary PCI and 24 and 96 h later, we determined serum hydrogen peroxide concentrations, plasma levels of the oxidative DNA adduct 8-hydroxy-2′-deoxyguanosine (8OHdG), tyrosine nitration, PARP activation, and translocation of apoptosis-inducing factor (AIF) in circulating leukocytes. Plasma 8OHdG levels and leukocyte tyrosine nitration were rapidly increased by PCI. Similarly, poly(ADP-ribose) content of the leukocytes increased in cells isolated just after PCI, indicating immediate PARP activation triggered by reperfusion of the myocardium. In contrast, serum hydrogen peroxide concentrations and the translocation of AIF gradually increased over time and were most pronounced at 96 h. Reperfusion-related oxidative/nitrosative stress triggers DNA damage, which leads to PARP activation in circulating leukocytes. Translocation of AIF and lipid peroxidation occurs at a later stage. These results represent the first direct demonstration of PARP activation in human myocardial infarction. Future work is required to test whether pharmacological inhibition of PARP may offer myocardial protection during primary PCI. PMID:17225870

  8. Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary reperfusion in human circulating leukocytes.

    PubMed

    Tóth-Zsámboki, Emese; Horváth, Eszter; Vargova, Katarina; Pankotai, Eszter; Murthy, Kanneganti; Zsengellér, Zsuzsanna; Bárány, Tamás; Pék, Tamás; Fekete, Katalin; Kiss, Róbert Gábor; Préda, István; Lacza, Zsombor; Gerö, Domokos; Szabó, Csaba

    2006-01-01

    Reactive free radical and oxidant production leads to DNA damage during myocardial ischemia/reperfusion. Consequent overactivation of poly(ADP-ribose) polymerase (PARP) promotes cellular energy deficit and necrosis. We hypothesized that PARP is activated in circulating leukocytes in patients with myocardial infarction and reperfusion during primary percutaneous coronary intervention (PCI). In 15 patients with ST segment elevation acute myocardial infarction, before and after primary PCI and 24 and 96 h later, we determined serum hydrogen peroxide concentrations, plasma levels of the oxidative DNA adduct 8-hydroxy-2'-deoxyguanosine (8OHdG), tyrosine nitration, PARP activation, and translocation of apoptosis-inducing factor (AIF) in circulating leukocytes. Plasma 8OHdG levels and leukocyte tyrosine nitration were rapidly increased by PCI. Similarly, poly(ADP-ribose) content of the leukocytes increased in cells isolated just after PCI, indicating immediate PARP activation triggered by reperfusion of the myocardium. In contrast, serum hydrogen peroxide concentrations and the translocation of AIF gradually increased over time and were most pronounced at 96 h. Reperfusion-related oxidative/nitrosative stress triggers DNA damage, which leads to PARP activation in circulating leukocytes. Translocation of AIF and lipid peroxidation occurs at a later stage. These results represent the first direct demonstration of PARP activation in human myocardial infarction. Future work is required to test whether pharmacological inhibition of PARP may offer myocardial protection during primary PCI.

  9. Quality of myocardial reperfusion according to ischemic time and infarcted territory.

    PubMed

    Cura, Fernando; Albertal, Mariano; Thierer, Jorge; Escudero, Alejandro Garcia; Candiello, Alfonsina; Jozami, Samir; Baliño, Pablo Perez; Padilla, Lucio T; Trivi, Marcelo; Belardi, Jorge A

    2011-03-01

    The relationship of the ischemic time to primary angioplasty and the quality of myocardial reperfusion according to infarcted territory among patients with ST-segment elevation myocardial infarction (STEMI) is unclear. This study consisted of 140 patients with STEMI within 12 h from the symptom onset and undergoing a primary angioplasty from the Protection of Distal Embolization in High-Risk Patients with Acute ST-Segment Elevation Myocardial Infarction Trial. ST-segment resolution (STR) at 60 min was analyzed by an independent corelab using continuous ST monitoring. Patients were divided according to anterior (n=74) and nonanterior (n=64) locations and according to ischemic time in quartiles (<90, 90-148, 148-241, and 241-635 min). Although there was no significant decrement in the extent of STR with the ischemic time in the entire population (74, 51, 72, and 51%, respectively, P=not significant), patients with anterior location have a significant reduction in the extent of STR after 90 min compared with those coming after 90 min (70.6 vs. 29.2% of complete STR, P=0.003, respectively). Patients with anterior STEMI seem to have a stronger impact of ischemic time on the quality of myocardial reperfusion compared with patients with nonanterior location.

  10. Ablation of cereblon attenuates myocardial ischemia-reperfusion injury.

    PubMed

    Kim, Jooyeon; Lee, Kwang Min; Park, Chul-Seung; Park, Woo Jin

    2014-05-16

    Cereblon (CRBN) was originally identified as a target protein for a mild type of mental retardation in humans. However, recent studies showed that CRBN acts as a negative regulator of AMP-activated protein kinase (AMPK) by binding directly to the AMPK catalytic subunit. Because AMPK is implicated in myocardial ischemia-reperfusion (I-R) injury, we reasoned that CRBN might play a role in the pathology of myocardial I-R through regulation of AMPK activity. To test this hypothesis, wild-type (WT) and crbn knockout (KO) mice were subjected to I-R (complete ligation of the coronary artery for 30 min followed by 24h of reperfusion). We found significantly smaller infarct sizes and less fibrosis in the hearts of KO mice than in those of WT mice. Apoptosis was also significantly reduced in the KO mice compared with that in WT mice, as shown by the reduced numbers of TUNEL-positive cells. In parallel, AMPK activity remained at normal levels in KO mice undergoing I-R, whereas it was significantly reduced in WT mice under the same conditions. In rat neonatal cardiomyocytes, overexpression of CRBN significantly reduced AMPK activity, as demonstrated by reductions in both phosphorylation levels of AMPK and the expression of its downstream target genes. Collectively, these data demonstrate that CRBN plays an important role in myocardial I-R injury through modulation of AMPK activity.

  11. Sex Differences in Reperfusion in Young Patients With ST-Segment–Elevation Myocardial Infarction Results From the VIRGO Study

    PubMed Central

    D’Onofrio, Gail; Safdar, Basmah; Lichtman, Judith H.; Strait, Kelly M.; Dreyer, Rachel P.; Geda, Mary; Spertus, John A.; Krumholz, Harlan M.

    2015-01-01

    Background Sex disparities in reperfusion therapy for patients with acute ST-segment–elevation myocardial infarction have been documented. However, little is known about whether these patterns exist in the comparison of young women with men. Methods and Results We examined sex differences in rates, types of reperfusion therapy, and proportion of patients exceeding American Heart Association reperfusion time guidelines for ST-segment–elevation myocardial infarction in a prospective observational cohort study (2008–2012) of 1465 patients 18 to 55 years of age, as part of the US Variations in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study at 103 hospitals enrolling in a 2:1 ratio of women to men. Of the 1238 patients eligible for reperfusion, women were more likely to be untreated than men (9% versus 4%, P=0.002). There was no difference in reperfusion strategy for the 695 women and 458 men treated. Women were more likely to exceed in-hospital and transfer time guidelines for percutaneous coronary intervention than men (41% versus 29%; odds ratio, 1.65; 95% confidence interval, 1.27–2.16), more so when transferred (67% versus 44%; odds ratio, 2.63; 95% confidence interval, 1.17–4.07); and more likely to exceed door-to-needle times (67% versus 37%; odds ratio, 2.62; 95% confidence interval, 1.23–2.18). After adjustment for sociodemographic, clinical, and organizational factors, sex remained an important factor in exceeding reperfusion guidelines (odds ratio, 1.72; 95% confidence interval, 1.28–2.33). Conclusions Young women with ST-segment–elevation myocardial infarction are less likely to receive reperfusion therapy and more likely to have reperfusion delays than similarly aged men. Sex disparities are more pronounced among patients transferred to percutaneous coronary intervention institutions or who received fibrinolytic therapy. PMID:25792558

  12. Sevoflurane preconditioning during myocardial ischemia-reperfusion reduces infarct size and preserves autonomic control of circulation in rats.

    PubMed

    Pasqualin, Rubens Campana; Mostarda, Cristiano Teixeira; Souza, Leandro Ezequiel de; Vane, Matheus Fachini; Sirvente, Raquel; Otsuki, Denise Aya; Torres, Marcelo Luís Abramides; Irigoyen, Maria Cláudia Costa; Auler, José Otávio Costa

    2016-05-01

    To investigate the myocardial ischemia-reperfusion with sevoflurane anesthetic preconditioning (APC) would present beneficial effects on autonomic and cardiac function indexes after the acute phase of a myocardial ischemia-reperfusion. Twenty Wistar rats were allocated in three groups: control (CON, n=10), myocardial infarction with sevoflurane (SEV, n=5) and infarcted without sevoflurane (INF, n=5). Myocardial ischemia (60 min) and reperfusion were performed by temporary coronary occlusion. Twenty-one days later, the systolic and diastolic function were evaluated by echocardiography; spectral analysis of the systolic arterial pressure (SAPV) and heart rate variability (HRV) were assessed. After the recording period, the infarct size (IS) was evaluated. The INF group presented greater cardiac dysfunction and increased sympathetic modulation of the SAPV, as well as decreased alpha index and worse vagal modulation of the HRV. The SEV group exhibited attenuation of the systolic and diastolic dysfunction and preserved vagal modulation (square root of the mean squared differences of successive R-R intervals and high frequency) of HRV, as well as a smaller IS. Sevoflurane preconditioning better preserved the cardiac function and autonomic modulation of the heart in post-acute myocardial infarction period.

  13. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-01-01

    Background: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. Methods: In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Results: Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Conclusion: Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice. PMID:26950150

  14. Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice

    PubMed Central

    Wu, B; Meng, K; Ji, Q; Cheng, M; Yu, K; Zhao, X; Tony, H; Liu, Y; Zhou, Y; Chang, C; Zhong, Y; Zhu, Z; Zhang, W; Mao, X; Zeng, Q

    2014-01-01

    Innate immune and inflammatory responses are involved in myocardial ischaemia/reperfusion (I/R) injury. Interleukin (IL)-37 is a newly identified member of the IL-1 family, and functions as a fundamental inhibitor of innate immunity and inflammation. However, its role in myocardial I/R injury remains unknown. I/R or sham operations were performed on male C57BL/6J mice. I/R mice received an injection of recombinant human IL-37 or vehicle, immediately before reperfusion. Compared with vehicle treatment, mice treated with IL-37 showed an obvious amelioration of the I/R injury, as demonstrated by reduced infarct size, decreased cardiac troponin T level and improved cardiac function. This protective effect was associated with the ability of IL-37 to suppress production of proinflammatory cytokines, chemokines and neutrophil infiltration, which together contributed to a decrease in cardiomyocyte apoptosis and reactive oxygen species (ROS) generation. In addition, we found that IL-37 inhibited the up-regulation of Toll-like receptor (TLR)-4 expression and nuclear factor kappa B (NF-kB) activation after I/R, while increasing the anti-inflammatory IL-10 level. Moreover, the administration of anti-IL-10R antibody abolished the protective effects of IL-37 in I/R injury. In-vitro experiments further demonstrated that IL-37 protected cardiomyocytes from apoptosis under I/R condition, and suppressed the migration ability of neutrophils towards the chemokine LIX. In conclusion, IL-37 plays a protective role against mouse myocardial I/R injury, offering a promising therapeutic medium for myocardial I/R injury. PMID:24527881

  15. A Multidisciplinary Assessment of Remote Myocardial Fibrosis After Reperfused Myocardial Infarction in Swine and Patients.

    PubMed

    Hervas, Arantxa; Ruiz-Sauri, Amparo; Gavara, Jose; Monmeneu, Jose V; de Dios, Elena; Rios-Navarro, Cesar; Perez-Sole, Nerea; Perez, Itziar; Monleon, Daniel; Morales, Jose M; Minana, Gema; Nunez, Julio; Bonanad, Clara; Diaz, Ana; Vila, Jose M; Chorro, Francisco J; Bodi, Vicente

    2016-08-01

    In extensive nonreperfused myocardial infarction (MI), remote fibrosis has been documented. Early reperfusion by primary angioplasty represents the gold standard method to minimize the extension of the infarction. We aimed to ascertain whether fibrosis also affects remote regions in reperfused MI in swine and patients. Swine were subjected to a transient occlusion of the left anterior descending artery followed by 1-week or 1-month reperfusion. Collagen content in the remote area macroscopically, microscopically, by magnetic resonance microimaging, and at the molecular level was similar to controls. In patients with previous MI, samples from autopsies displayed a significant increase in collagen content only in the infarct region. In patients with previous MI submitted to cardiac magnetic resonance-T1 mapping, the extracellular volume fraction in remote segments was similar to that for controls. In all scenarios, the remote region did not show a significant increase of collagen content in comparison with controls.

  16. Rho-Kinase Activation in Leukocytes Plays a Pivotal Role in Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Kitano, Katsunori; Usui, Soichiro; Ootsuji, Hiroshi; Takashima, Shin-ichiro; Kobayashi, Daisuke; Murai, Hisayoshi; Furusho, Hiroshi; Nomura, Ayano; Kaneko, Shuichi; Takamura, Masayuki

    2014-01-01

    The Rho/Rho-kinase pathway plays an important role in many cardiovascular diseases such as hypertension, atherosclerosis, heart failure, and myocardial infarction. Although previous studies have shown that Rho-kinase inhibitors reduce ischemia/reperfusion (I/R) injury and cytokine production, the role of Rho-kinase in leukocytes during I/R injury is not well understood. Mice were subjected to 30-min ischemia and reperfusion. Rho-kinase activity was significantly greater in leukocytes subjected to myocardial I/R compared to the sham-operated mice. Administration of fasudil, a Rho-kinase inhibitor, significantly reduced the I/R-induced expression of the proinflammatory cytokines interleukin (IL)-6, C-C motif chemoattractant ligand 2 (CCL2), and tumor necrosis factor (TNF)-α, in leukocytes, compared with saline as the vehicle. Furthermore, fasudil decreased I/R-induced myocardial infarction/area at risk (IA) and I/R-induced leukocyte infiltration in the myocardium. Interestingly, IA in fasudil-administered mice with leukocyte depletion was similar to that in fasudil-administered mice. I/R also resulted in remarkable increases in the mRNA expression levels of the proinflammatory cytokines TNF-α, IL-6, and CCL2 in the heart. Inhibition of Rho-kinase activation in leukocytes has an important role in fasudil-induced cardioprotective effects. Hence, inhibition of Rho-kinase may be an additional therapeutic intervention for the treatment of acute coronary syndrome. PMID:24638037

  17. High-sensitivity troponin T predicts infarct scar characteristics and adverse left ventricular function by cardiac magnetic resonance imaging early after reperfused acute myocardial infarction.

    PubMed

    Nguyen, Tuan L; Phan, Justin A K; Hee, Leia; Moses, Daniel A; Otton, James; Terreblanche, Owen D; Xiong, Jessica; Premawardhana, Upul; Rajaratnam, Rohan; Juergens, Craig P; Dimitri, Hany R; French, John K; Richards, David A B; Thomas, Liza

    2015-10-01

    Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) is the current standard for evaluation of myocardial infarct scar size and characteristics. Because post-ST-segment elevation myocardial infarction (STEMI) troponin levels correlate with clinical outcomes, we sought to determine the sampling period for high-sensitivity troponin T (hs-TnT) that would best predict CMRI-measured infarct scar characteristics and left ventricular (LV) function. Among 201 patients with first presentation with STEMI who were prospectively recruited, we measured serial hs-TnT levels at admission, peak, 24 hours, 48 hours, and 72 hours after STEMI. Indexed LV volumes, LV ejection fraction (LVEF) and infarct scar characteristics (scar size, scar heterogeneity, myocardial salvage index, and microvascular obstruction) were evaluated by CMRI at a median of 4 days post-STEMI. Peak and serial hs-TnT levels correlated positively with early indexed LV volumes and infarct scar characteristics, and negatively correlated with myocardial salvage index and LVEF. Both 48- and 72-hour hs-TnT levels similarly predicted "large" total infarct scar size (odds ratios [ORs] 3.08 and 3.53, both P < .001), myocardial salvage index (ORs 1.68 and 2.30, both P < .001), and LVEF <40% (ORs 2.16 and 2.17, both P < .001) on univariate analyses. On multivariate analyses, 48- and 72-hour hs-TnT levels independently predicted large infarct scar size (ORs 2.05 and 2.31, both P < .001), reduced myocardial salvage index (OR 1.39 [P = .031] and OR 1.55 [P = .009]), and LVEF <40% (OR 1.47 [P = .018] and OR 1.43 [P = .026]). All measured hs-TnT levels had a modest association and similar capacity to predict microvascular obstruction. Levels of hs-TnT at 48 and 72 hours, measured during the "plateau phase" post-STEMI, predicted infarct scar size, poor myocardial salvage, and LVEF. These levels also correlated with scar heterogeneity and microvascular obstruction post-STEMI. Since ascertaining peak levels after

  18. Garlicin post-conditioning suppresses adhesion molecules in a porcine model of myocardial ischemia-reperfusion injury.

    PubMed

    Yang, Peng; Li, Jia-Hui; Li, Ai-Li; Li, Jing; Wang, Yong; Ren, Shi-Yan; Li, Xian-Lun

    2017-05-11

    To evaluate whether garlicin post-conditioning can attenuate myocardial ischemiareperfusion injury in a catheter-based porcine model of acute myocardial infarction (AMI) by affecting adhesion molecules integrin β1/CD29 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). Twenty-two swine were devided into 3 groups: 6 in a sham-operation group, and 8 each in the model and garlicin groups. AMI porcine model was established in the model and garlicin groups. The distal parts of the left anterior descending coronary artery in the animals of the model and garlicin groups were occluded by dilated balloon for 2 h, followed by reperfusion for 3 h. Garlicin (1.88 mg/kg) was injected over a period of 1 h, beginning just before reperfusion, in the garlicin group. Real-time polymerase chain reaction, immunohistochemistry and Western blot were carried out to detect mRNA and protein expressions of CD29 and CD31 3 h after reperfusion. Hematoxylin-eosin staining showed a better myocardial structure in the garlicin group after reperfusion. Compared to the model group, garlicin inhibited both the mRNA and protein expression of CD29 and CD31 in reperfusion area and no-reflflow area (P<0.05 respectively). Garlicin post-conditioning induced cardio-protection against myocardial ischemia-reperfusion injury in this catheter-based porcine model of AMI. The cardio-protective effect of garlicin is possibly owing to suppression of production of CD29 and CD31, by inhibition of the mRNA expression of CD29 and CD31.

  19. The effect of Euryale ferox (Makhana), an herb of aquatic origin, on myocardial ischemic reperfusion injury.

    PubMed

    Das, Samarjit; Der, Peter; Raychaudhuri, Utpal; Maulik, Nilanjana; Das, Dipak K

    2006-09-01

    Fox nut or gorgon nut (Euryale ferox--Family Nymphaeaceae), popularly known as Makhana, has been widely used in traditional oriental medicine to cure a variety of diseases including kidney problems, chronic diarrhea, excessive leucorrhea and hypofunction of the spleen. Based on the recent studies revealing antioxidant activities of Euryale ferox and its glucosides composition, we sought to determine if Euryale ferox seeds (Makhana) could reduce myocardial ischemic reperfusion injury. Two different models were used: acute model, where isolated rat hearts were preperfused for 15 min with Krebs Henseleit bicarbonate (KHB) buffer containing three different doses of makhana (25, 125 or 250 microg/ml) followed by 30 min of ischemia and 2 h of reperfusion; and chronic model, where rats were given two different doses of makhana (250 and 500 mg/kg/day) for 21 days, after which isolated hearts were subjected to 30 min of ischemia followed by 2 h of reperfusion. In both cases, the hearts of the Makhana treated rats were resistant to ischemic reperfusion injury as evidenced by their improved post-ischemic ventricular function and reduced myocardial infarct size. Antibody array technique was used to identify the cardioprotective proteins. The Makhana-treated hearts had increased amounts of thioredoxin-1 (Trx-1) and thioredoxin-related protein-32 (TRP32) compared to the control hearts. Western blot analysis confirmed increased expression of TRP32 and thioredoxin proteins. In vitro studies revealed that Makhana extracts had potent reactive oxygen species scavenging activities. Taken together, the results of this study demonstrate cardioprotective properties of Makhana and suggest that such cardioprotective properties may be linked with the ability of makhana to induce TRP32 and Trx-1 proteins and to scavenge ROS.

  20. The treatment of acute myocardial infarction: the Past, the Present, and the Future.

    PubMed

    Braunwald, Eugene

    2012-04-01

    Since Herrick's description of the clinical picture of acute myocardial infarction exactly one century ago (1912), there have been three phases of therapy: Phase 1 (1912-1961, bed rest and 'expectant' treatment); Phase 2 (1961-1974, the coronary care unit); and Phase 3 (1975-present, myocardial reperfusion). We are now on the cusp of Phase 4, which comprises efforts to reduce myocardial perfusion injury as well as regenerative medicine.

  1. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

    PubMed

    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-03-21

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia/reperfusion injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. Here we found that glucose uptake was remarkably diminished in myocardium following reperfusion in Sprague-Dawley rats as detected by 18F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by 3 folds and GLUT4 translocation remained unchanged compared with those of sham rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated ischemia/reperfusion injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, while its knockdown increased glucose uptake, suggesting a role of PDK4 in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial ischemia/reperfusion. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial ischemia/reperfusion injury.

  2. Cardioprotective Effects of Total Flavonoids Extracted from Xinjiang Sprig Rosa rugosa against Acute Ischemia/Reperfusion-Induced Myocardial Injury in Isolated Rat Heart.

    PubMed

    Hou, Xuejiao; Han, Jichun; Yuan, Changsheng; Ren, Huanhuan; Zhang, Ya; Zhang, Tao; Xu, Lixia; Zheng, Qiusheng; Chen, Wen

    2016-01-01

    This study evaluated the antioxidative and cardioprotective effects of total flavonoids extracted from Xinjiang sprig Rosa rugosa on ischemia/reperfusion (I/R) injury using an isolated Langendorff rat heart model. The possible mechanism of Xinjiang sprig rose total flavonoid (XSRTF) against I/R injury was also studied. XSRTF (5, 10, and 20 µg/mL) dissolved in Krebs-Henseleit buffer was administered to isolated rat heart. The XSRTF showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and superoxide anion radicals in vitro. XSRTF pretreatment improved the heart rate, increased LVDP, and decreased CK and LDH levels in coronary flow. This pretreatment also increased SOD activity and GSH/GSSG ratio but decreased MDA, TNF-α, and CRP levels and IL-8 and IL-6 activities. The infarct size and cell apoptosis in the hearts from the XSRTF-treated group were lower than those in the hearts from the I/R group. Therefore, the cardioprotective effects of XSRTF may be attributed to its antioxidant, antiapoptotic, and anti-inflammatory activities.

  3. Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury.

    PubMed

    Gorsuch, W Brian; Guikema, Benjamin J; Fritzinger, David C; Vogel, Carl-Wilhelm; Stahl, Gregory L

    2009-12-01

    Cobra venom factor (CVF) is a complement activating protein in cobra venom, which functionally resembles C3b, and has been used for decades for decomplementation of serum to investigate the role of complement in many model systems of disease. The use of CVF for clinical practice is considered impractical because of immunogenicity issues. Humanization of CVF was recently demonstrated to yield a potent CVF-like molecule. In the present study, we demonstrate that mice treated with recombinant humanized CVF (HC3-1496) are protected from myocardial ischemia-reperfusion (MI/R) injuries with resultant preservation of cardiac function. Also, C3 deposition in the myocardium following MI/R was not observed following treatment with HC3-1496. HC3-1496 led to complement activation and depletion of C3, but preserved C5 titers. These data suggest, unlike CVF, HC3-1496 does not form a C5 convertase in the mouse, similar to recent studies in human sera/plasma. These results suggest that humanized CVF (HC3-1496) protects the ischemic myocardium from reperfusion injuries induced by complement activation and represents a novel anti-complement therapy for potential clinical use.

  4. Large myocardial infarction with myocardium calcium deposits associated with reperfusion injury.

    PubMed

    Rios, Elisabete; Mancio, Jennifer; Rodrigues-Pereira, Pedro; Magalhães, Domingos; Bartosch, Carla

    2014-01-01

    The clinical and autopsy findings of a 66-year-old man with myocardial infarction complicated by reperfusion injury are described, highlighting the presence of large myocardium calcium deposits. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Pharmaco-mechanic antithrombotic strategies to reperfusion of the infarct-related artery in patients with ST-elevation acute myocardial infarctions.

    PubMed

    Kala, Petr; Miklik, Roman

    2013-06-01

    Primary percutaneous coronary intervention is the best treatment of patients with ST elevation myocardial infarction (STEMI). When managing a STEMI patient, our approach must be rapid and aggresive in order to interrupt the pathological process of thrombus formation and stabilization. The therapy must be initiated prior to angiography (pretreatment), continued during the procedure (periprocedural), recovery phase (in-hospital), and follow-up. The treatment strategies resulting in thrombus dissolution/extraction have focused on optimization of both pharmacological and interventional therapies. At present, there is no optimal evidence-based approach to all patients with STEMI, and the treatment of these patients needs to be modified with respect to the risk profile, availability of medical resources, and our experience. In this review, we summarize current pharmacological and interventional strategies used in the setting of STEMI and discuss potential benefits of novel dosing regimens and combinations of drugs and techniques.

  6. Ilexsaponin A attenuates ischemia-reperfusion-induced myocardial injury through anti-apoptotic pathway

    PubMed Central

    Wang, Fang; Qiang, Jiao; Liu, Pan; Zhang, Jun; Xu, Jin-Wen

    2017-01-01

    The protective effects of ilexsaponin A on ischemia-reperfusion-induced myocardial injury were investigated. Myocardial ischemia/reperfusion model was established in male Sprague–Dawley rats. Myocardial injury was evaluated by TTC staining and myocardial marker enzyme leakage. The in vitro protective potential of Ilexsaponin A was assessed on hypoxia/reoxygenation cellular model in neonatal rat cardiomyocytes. Cellular viability and apoptosis were evaluated by MTT and TUNEL assay. Caspase-3, cleaved caspase-3, bax, bcl-2, p-Akt and Akt protein expression levels were detected by western-blot. Ilexsaponin A treatment was able to attenuate the myocardial injury in ischemia/reperfusion model by reducing myocardial infarct size and lower the serum levels of LDH, AST and CK-MB. The in vitro study also showed that ilexsaponin A treatment could increase cellular viability and inhibit apoptosis in hypoxia/reoxygenation cardiomyocytes. Proapoptotic proteins including caspase-3, cleaved caspase-3 and bax were significantly reduced and anti-apoptotic protein bcl-2 was significantly increased by ilexsaponin A treatment in hypoxia/reoxygenation cardiomyocytes. Moreover, Ilexsaponin A treatment was able to increase the expression levels of p-Akt in hypoxia/reoxygenation cellular model and myocardial ischemia/reperfusion animal model. Coupled results from both in vivo and in vitro experiments indicate that Ilexsaponin A attenuates ischemia-reperfusion-induced myocardial injury through anti-apoptotic pathway. PMID:28182689

  7. Protective Effects of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Injury in VIVO.

    PubMed

    Di Paola, Rosanna; Cordaro, Marika; Crupi, Rosalia; Siracusa, Rosalba; Campolo, Michela; Bruschetta, Giuseppe; Fusco, Roberta; Pugliatti, Pietro; Esposito, Emanuela; Cuzzocrea, Salvatore

    2016-08-01

    Myocardial infarction is the leading cause of death, occurs after prolonged ischemia of the coronary arteries. Restore blood flow is the first intervention help against heart attack. However, reperfusion of the arteries leads to ischemia/reperfusion injury (I/R). The fatty acid amide palmitoylethanolamide (PEA) is an endogenous compound widely present in living organisms, with analgesic and anti-inflammatory properties. The present study evaluated the effect of ultramicronized palmitoylethanolamide (PEA-um) treatment on the inflammatory process associated with myocardial I/R. Myocardial ischemia reperfusion injury was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. PEA-um, was administered (10 mg/kg) 15 min after ischemia and 1 h after reperfusion. In this study, we demonstrated that PEA-um treatment reduces myocardial tissue injury, neutrophil infiltration, adhesion molecules (ICAM-1, P-selectin) expression, proinflammatory cytokines (TNF-α, IL-1β) production, nitrotyrosine and PAR formation, nuclear factor kB expression, and apoptosis (Fas-L, Bcl-2) activation. In addition to study whether the protective effect of PEA-um on myocardial ischemia reperfusion injury is also related to the activation of PPAR-α, in a separate set of experiments it has been performed myocardial I/R in PPARα mice. Genetic ablation of peroxisome proliferator activated receptor (PPAR)-α in PPAR-αKO mice exacerbated Myocardial ischemia reperfusion injury when compared with PPAR-αWT mice. PEA-um induced cardioprotection in PPAR-α wild-type mice, but the same effect cannot be observed in PPAR-αKO mice. Our results have clearly shown a modulation of the inflammatory process, associated with myocardial ischemia reperfusion injury, following administration of PEA-um.

  8. Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction.

    PubMed

    Olea, Fernanda D; De Lorenzi, Andrea; Cortés, Claudia; Cuniberti, Luis; Fazzi, Lucía; Flamenco, María del Pilar; Locatelli, Paola; Cabeza Meckert, Patricia; Bercovich, Andrés; Laguens, Rubén; Crottogini, Alberto

    2013-05-10

    In reperfused acute myocardial infarction (RAMI), cardioprotective treatments may enhance myocardial salvage and hence reduce the area of necrosis. Based on studies showing that plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic actions in animal models of AMI, we aimed to assess if their association would reduce infarct size to a larger extent than any of them individually in a large mammalian model of RAMI. Adult sheep subjected to 90-minute coronary artery occlusion received upon reperfusion intramyocardial pVEGF 3.8 mg plus intravenous EPO 1000 IU/kg (n=8), pVEGF (n=8), EPO (n=8) or placebo (n=8). Fifteen days after treatment, infarct size was smaller in the 3 treatment groups (pVEGF+EPO: 8 ± 1 %; pVEGF: 16 ± 5 %; EPO: 13 ± 4 %) compared to placebo (25 ± 7 %, p<0.001). However, in the EPO+VEGF group infarct size was significantly smaller than in the groups receiving EPO or VEGF individually (p<0.05). DNA fragmentation, a hallmark of late apoptosis, was significantly lower in sheep receiving EPO. The combined treatment, while not affecting global left ventricular performance, improved regional peri-infarct function and prevented over-time expansion of the post-infarct perfusion defect. Combined pVEGF and EPO treatment might be clinically useful to enhance the benefits of early revascularization in patients with acute myocardial infarction. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Myocardial hypoperfusion/reperfusion tolerance with exercise training in hypertension.

    PubMed

    Reger, Patricia O; Barbe, Mary F; Amin, Mamta; Renna, Brian F; Hewston, Leigh Ann; MacDonnell, Scott M; Houser, Steven R; Libonati, Joseph R

    2006-02-01

    The purpose of this study was to examine whether exercise training, superimposed on compensated-concentric hypertrophy, could increase myocardial hypoperfusion-reperfusion (H/R) tolerance. Female Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (age: 4 mo; N = 40) were placed into a sedentary (SED) or exercise training (TRD) group (treadmill running; 25 m/min, 1 h/day, 5 days/wk for 16 wk). Four groups were studied: WKY-SED (n = 10), WKY-TRD (n = 10), SHR-SED (n = 10), and SHR-TRD (n = 10). Blood pressure and heart rate were determined, and in vitro isolated heart performance was measured with a retrogradely perfused, Langendorff isovolumic preparation. The H/R protocol consisted of a 75% reduction in coronary flow for 17 min followed by 30 min of reperfusion. Although the rate-pressure product was significantly elevated in SHR relative to WKY, training-induced bradycardia reduced the rate-pressure product in SHR-TRD (P < 0.05) without an attenuation in systolic blood pressure. Heart-to-body weight ratio was greater in both groups of SHR vs. WKY-SED (P < 0.001). Absolute and relative myocardial tolerance to H/R was greater in WKY-TRD and both groups of SHR relative to WKY-SED (P < 0.05). Endurance training superimposed on hypertension-induced compensated hypertrophy conferred no further cardioprotection to H/R. Postreperfusion 72-kDa heat shock protein abundance was enhanced in WKY-TRD and both groups of SHR relative to WKY-SED (P < 0.05) and was highly correlated with absolute left ventricular functional recovery during reperfusion (R2= 0.86, P < 0.0001). These data suggest that both compensated hypertrophy associated with short-term hypertension and endurance training individually improved H/R and that increased postreperfusion 72-kDa heat shock protein abundance was, in part, associated with the cardioprotective phenotype observed in this study.

  10. Oxygen surrounding the heart during ischemic conservation determines the myocardial injury during reperfusion.

    PubMed

    Feng, Yansheng; Bopassa, Jean Chrisostome

    2015-01-01

    There is discrepancy regarding the duration of reperfusion required using 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) staining to assess myocardial infarction in an isolated, perfused heart model. Several investigators prefer long-term reperfusion (120 minutes) to determine myocardial injury, while others have used a shorter duration (30-40 minutes). We investigated whether oxygen surrounding the myocardium during ischemia plays a critical role in the installation of myocardial infarction during reperfusion. Mice hearts were perfused with a Langendorff apparatus using Krebs Henseleit (KH) buffer oxygenated with 95% O2 plus 5% CO2 at 37°C. Hearts were either immersed in KH or suspended in air during 18 minutes of global ischemia in a normothermic, water-jacketed chamber. Hearts then were reperfused for 40, 60, or 90 minutes. We found that hearts immersed in KH had decreased recovery of function and increased myocardial infarct size, reaching a steady-state level after 40 minutes of reperfusion. In contrast, hearts suspended in air approached steady-state after 90 minutes of reperfusion. Thus, mitochondrial reactive oxygen species (ROS) production was much lower in air-maintained hearts than in KH-immersed hearts. To investigate whether an increase in oxygen surrounding the myocardium during ischemia might cause further damage, we bubbled the KH solution with nitrogen (KH+N2) rather than oxygen (KH+O2). With this alteration, recovery of cardiac function was improved and myocardial infarct size and mitochondrial ROS production were reduced compared with hearts immersed in KH+O2. In conclusion, short-term (40 minutes) reperfusion is sufficient to reach steady-state myocardial infarct size when hearts are immersed in physiologic solution during ischemia; however, a longer duration of reperfusion (90 minutes) is required if hearts are suspended in air. Thus, oxygen surrounding the heart during ischemia determines the extent of myocardium injury during reperfusion.

  11. Impact of an Interleukin-1 Receptor Antagonist and Erythropoietin on Experimental Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Grothusen, Christina; Hagemann, Angelika; Attmann, Tim; Braesen, Jan; Broch, Ole; Cremer, Jochen; Schoettler, Jan

    2012-01-01

    Background. Revascularization of infarcted myocardium results in release of inflammatory cytokines mediating myocardial reperfusion injury and heart failure. Blockage of inflammatory pathways dampens myocardial injury and reduces infarct size. We compared the impact of the interleukin-1 receptor antagonist Anakinra and erythropoietin on myocardial ischemia/reperfusion injury. In contrast to others, we hypothesized that drug administration prior to reperfusion reduces myocardial damage. Methods and Results. 12–15 week-old Lewis rats were subjected to myocardial ischemia by a 1 hr occlusion of the left anterior descending coronary artery. After 15 min of ischemia, a single shot of Anakinra (2 mg/kg body weight (bw)) or erythropoietin (5000 IE/kg bw) was administered intravenously. In contrast to erythropoietin, Anakinra decreased infarct size (P < 0.05, N = 4/group) and troponin T levels (P < 0.05, N = 4/group). Conclusion. One-time intravenous administration of Anakinra prior to myocardial reperfusion reduces infarct size in experimental ischemia/reperfusion injury. Thus, Anakinra may represent a treatment option in myocardial infarction prior to revascularization. PMID:22649318

  12. Tachyarrhythmias in acute myocardial infarction.

    PubMed

    McLean, K H; Bett, J N; Saltups, A

    1975-02-01

    In 1505 patients with acute myocardial infarction (MI) serious ventricular arrhythmias were commoner in those with transmural ECG changes, and were associated with an increase in mortality and in the incidence of left ventricular failure (LVF) as well as higher peak serum lactic dehydrogenase (LDH) levels. Atrial fibrillation (AF) occurred more often in older patients and in those with LVF and clinical evidence of pericarditis.

  13. 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

  14. High-molecular-weight polyethylene glycol inhibits myocardial ischemia-reperfusion injury in vivo.

    PubMed

    Xu, Xianyao; Philip, Jennifer L; Razzaque, Md Abdur; Lloyd, James W; Muller, Charlie M; Akhter, Shahab A

    2015-02-01

    Cardiac ischemia-reperfusion (I-R) injury remains a significant problem as there are no therapies available to minimize the cell death that can lead to impaired function and heart failure. We have shown that high-molecular-weight polyethylene glycol (PEG) (15-20 kD) can protect cardiac myocytes in vitro from hypoxia-reoxygenation injury. In this study, we investigated the potential protective effects of PEG in vivo. Adult rats underwent left anterior descending artery occlusion for 60 minutes followed by 48 hours or 4 weeks of reperfusion. One milliliter of 10% PEG solution or phosphate-buffered saline (PBS) control (n = 10 per group) was administered intravenously (IV) immediately before reperfusion. Fluorescein-labeled PEG was robustly visualized in the myocardium 1 hour after IV delivery. The PEG group had significant recovery of left ventricular ejection fraction at 4 weeks versus a 25% decline in the PBS group (P < .01). There was 50% less LV fibrosis in the PEG group versus PBS with smaller peri-infarct and remote territory fibrosis (P < .01). Cell survival signaling was upregulated in the PEG group with increased Akt (3-fold, P < .01) and ERK (4-fold, P < .05) phosphorylation compared to PBS controls at 48 hours. PEG also inhibited apoptosis as measured by TUNEL-positive nuclei (56% decrease, P < .02) and caspase 3 activity (55% decrease, P < .05). High-molecular-weight PEG appears to have a significant protective effect from I-R injury in the heart when administered IV immediately before reperfusion. This may have important clinical translation in the setting of acute coronary revascularization and myocardial protection in cardiac surgery. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  15. Infant acute myocarditis mimicking acute myocardial infarction

    PubMed Central

    Tilouche, Samia; Masmoudi, Tasnim; Sahnoun, Maha; Chkirbène, Youssef; Mestiri, Sarra; Boughamoura, Lamia; Ben Dhiab, Mohamed; Souguir, Mohamed Kamel

    2016-01-01

    Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis. PMID:28210569

  16. Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation

    NASA Astrophysics Data System (ADS)

    Nakano, Yasuhiro; Matoba, Tetsuya; Tokutome, Masaki; Funamoto, Daiki; Katsuki, Shunsuke; Ikeda, Gentaro; Nagaoka, Kazuhiro; Ishikita, Ayako; Nakano, Kaku; Koga, Jun-Ichiro; Sunagawa, Kenji; Egashira, Kensuke

    2016-07-01

    Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg-1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg-1), inhibits the recruitment of inflammatory monocytes to the IR heart, and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms, and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI.

  17. Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation

    PubMed Central

    Nakano, Yasuhiro; Matoba, Tetsuya; Tokutome, Masaki; Funamoto, Daiki; Katsuki, Shunsuke; Ikeda, Gentaro; Nagaoka, Kazuhiro; Ishikita, Ayako; Nakano, Kaku; Koga, Jun-ichiro; Sunagawa, Kenji; Egashira, Kensuke

    2016-01-01

    Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg−1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg−1), inhibits the recruitment of inflammatory monocytes to the IR heart, and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms, and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI. PMID:27403534

  18. Primary coronary angioplasty in patients with acute myocardial infarction.

    PubMed Central

    Popma, J J; Chuang, Y C; Satler, L F; Kleiber, B; Leon, M B

    1994-01-01

    In some patients with acute myocardial infarction, thrombolytic therapy may be limited by its failure to reperfuse the occluded artery, by recurrent ischemia (despite initially successful reperfusion), and by major hemorrhagic complications. Primary coronary angioplasty may circumvent these limitations. This article reviews the results of primary angioplasty reported in patients with myocardial infarction and makes recommendations for its use. The review includes pertinent articles found in the English language literature from July 1987 to July 1993 on MEDLINE. Nonrandomized series of primary angioplasty in acute myocardial infarction have demonstrated high procedural success rates (86% to 99%) and infrequent recurrent ischemia (4%). Two randomized trials comparing primary angioplasty and thrombolytic therapy have shown that primary angioplasty results in lower mortality, less recurrent ischemia, shorter length of hospital stay, and improved left ventricular function. Two other randomized studies have shown little benefit from primary angioplasty on myocardial salvage, recurrent ischemia, or ventricular function. One major limitation of primary angioplasty is that it requires 24-hour availability of a catheterization laboratory and experienced surgical personnel. Primary angioplasty may be the preferred approach in patients with extensive myocardial infarction who have immediate (< 120 min) access to a cardiac catheterization laboratory with experienced personnel. Patients having 1) contraindications to thrombolytic therapy, 2) cardiogenic shock, 3) prior coronary bypass surgery, or 4) "stuttering" onset of pain may also benefit from primary angioplasty. Poor candidates for this procedure are those with a small myocardial infarction, those in whom undue delays in access to a cardiac catheterization facility would be expected, or those with complex coronary anatomy, including left main coronary artery disease. PMID:8061539

  19. Pharmacological preconditioning with hyperbaric oxygen: can this therapy attenuate myocardial ischemic reperfusion injury and induce myocardial protection via nitric oxide?

    PubMed

    Yogaratnam, Jeysen Zivan; Laden, Gerard; Guvendik, Lavent; Cowen, Mike; Cale, Alex; Griffin, Steve

    2008-09-01

    Ischemic reperfusion injury (IRI) is an inevitable part cardiac surgery such as coronary artery bypass graft (CABG). While ischemic hypoxia and the ensuing normoxic or hyperoxic reperfusion are critical to the initiation and propagation of IRI, conditioning myocardial cells to an oxidative stress prior to IRI may limit the consequences of this injury. Hyperbaric oxygen (HBO2) is a modality of treatment that is known to generate an oxidative stress. Studies have shown that treatment with HBO2 postischemia and reperfusion is useful in ameliorating myocardial IRI. Moreover, preconditioning the myocardium with HBO2 before reperfusion has demonstrated a myocardial protective effect by limiting the infarct size post ischemia and reperfusion. Current evidence suggests that HBO2 preconditioning may partly attenuate IRI by stimulating the endogenous production of nitric oxide (NO). As NO has the capacity to reduce neutrophil sequestration, adhesion and associated injury, and improve vascular flow, HBO2 preconditioning induced NO may play a role in providing myocardial protection during interventions that involve an inevitable episode of IRI. This current opinion review article attempts to suggest that HBO2 may be used to pharmacologically precondition and protect the myocardium from the effects of IRI that is known to occur during cardiac surgery.

  20. Ventricular septal rupture following acute myocardial infarction.

    PubMed

    Koh, Angela S; Loh, Yee Jim; Lim, Yeong Phang; Le Tan, Ju

    2011-04-01

    Ventricular septal rupture (VSR) is a complication of acute myocardial infarction (AMI) that is associated with significant mortality. We aim to review the clinical outcome in the current era. Patients admitted to a single tertiary centre from 1997 to 2008 with VSR post-AMI were identified from the local cardiac registry. We performed a retrospective review on 25 patients. Mean age (15 women) was 71 years. Most patients had cardiovascular risk factors (84%); the commonest was hypertension (72%). Anterior AMI (80%) and apical VSR (84%) formed the majority of the cases. Eleven patients (44%) received prior coronary reperfusion therapy either via thrombolysis or PCI. Median time to rupture was 1 day from diagnosis of infarction. More than half (60%) of the patients were in Killip class 3 or 4 at diagnosis of rupture. Mean left ventricular ejection fraction (LVEF) was 33 +/- 10%. Most patients (80%) required IABP for haemodynamic support. All patients who underwent surgery had ventricular septal repair; amongst them 47% had concomitant CABG. Those managed conservatively were older (P = 0.01). Overall mortality rate was 44%. Most died within the first four days (82%). Surgical and non-surgical survival rates were 68% and 17%, respectively (P= 0.039). Patient demographics, prior coronary reperfusion techniques, Killip class status and LVEF were not significant predictors of mortality. However, non-anterior wall AMI and non-apical VSR were significantly associated with poorer survival (P = 0.009, P = 0.026 respectively). While the occurrence ofVSR post-AMI appears to be low compared to earlier studies, it continues to be associated with significant mortality. Non-anterior wall AMI and non-apical VSR were associated with poorer survival and surgical repair conferred survival advantage over conservative management.

  1. A History of Streptokinase Use in Acute Myocardial Infarction

    PubMed Central

    Sikri, Nikhil; Bardia, Amit

    2007-01-01

    A serendipitous discovery by William Smith Tillett in 1933, followed by many years of work with his student Sol Sherry, laid a sound foundation for the use of streptokinase as a thrombolytic agent in the treatment of acute myocardial infarction. The drug found initial clinical application in combating fibrinous pleural exudates, hemothorax, and tuberculous meningitis. In 1958, Sherry and others started using streptokinase in patients with acute myocardial infarction and changed the focus of treatment from palliation to “cure.” Initial trials that used streptokinase infusion produced conflicting results. An innovative approach of intracoronary streptokinase infusion was initiated by Rentrop and colleagues in 1979. Subsequently, larger trials of intracoronary infusion achieved reperfusion rates ranging from 70% to 90%. The need for a meticulously planned and systematically executed randomized multicenter trial was fulfilled by the Gruppo Italiano per la Sperimentazione della Streptochinasi nell'Infarto Miocardico (GISSI) trial in 1986, which not only validated streptokinase as an effective therapeutic method but also established a fixed protocol for its use in acute myocardial infarction. Currently, despite the wide use of tissue plasminogen activator in developed nations, streptokinase remains essential to the management of acute myocardial infarction in developing nations. PMID:17948083

  2. Myocardial revascularisation after acute myocardial infarction.

    PubMed

    Bana, A; Yadava, O P; Ghadiok, R; Selot, N

    1999-05-15

    One hundred and twenty-three patients had coronary artery bypass grafting (CABG) within 30 days of acute myocardial infarction (AMI) from May 1992 to November 1997. Commonest infarct was anterior transmural (61.8%) and commonest indication of surgery was post-infarct persistent or recurrent angina (69.1%). Ten patients were operated within 48 h and 36 between 48 h to 2 weeks of having MI. Out of these, nine patients were having infarct extension and cardiogenic shock at the time of surgery. Pre-operatively fourteen patients were on inotropes of which six also had intra-aortic balloon pump (IABP) support. All patients had complete revascularisation with 3.8+/-1.2 distal anastomoses per patient. By multivariate analysis, we found that independent predictors of post-operative morbidity [inotropes >48 h, use of IABP, ventilation >24 h, ICU stay >5 days] and complications [re-exploration, arrhythmias, pulmonary complications, wound infection, cerebrovascular accident (CVA)] were left ventricular ejection fraction (LVEF) <30%, Q-wave MI, surgery <48 h after AMI, presence of pre-operative cardiogenic shock and age >60 years (P < or = 0.01). Mortality at 30 days was 3.3%. LVEF <30%, Q-wave MI, surgery <48 h after AMI, presence of pre-operative cardiogenic shock and age >60 years were found to be independent predictors of 30 days mortality (P < or = 0.01). Ninety patients were followed up for a mean duration of 33 months (1 to 65 months). There were three late deaths and five patients developed recurrence of angina. To conclude, CABG can be carried out with low risk following AMI in stable patients for post-infarct angina. Patients who undergo urgent or emergent surgery and who have pre-operative cardiogenic shock, IABP, poor left ventricular functions, age >60 years and Q-wave MI are at increased risk.

  3. Amelioration of myocardial ischemic reperfusion injury with Calendula officinalis.

    PubMed

    Ray, Diptarka; Mukherjee, Subhendu; Falchi, Mario; Bertelli, Aldo; Das, Dipak K

    2010-12-01

    Calendula officinalis of family Asteraceae, also known as marigold, has been widely used from time immemorial in Indian and Arabic cultures as an anti-inflammatory agent to treat minor skin wound and infections, burns, bee stings, sunburn and cancer. At a relatively high dose, calendula can lower blood pressure and cholesterol. Since inflammatory responses are behind many cardiac diseases, we sought to evaluate if calendula could be cardioprotective against ischemic heart disease Two groups of hearts were used: the treated rat hearts were perfused with calendula solution at 50 mM in KHB buffer (in mM: sodium chloride 118, potassium chloride 4.7, calcium chloride 1.7, sodium bicarbonate 25, potassium biphosphate 0.36, magnesium sulfate 1.2, and glucose 10) for 15 min prior to subjecting the heart to ischemia, while the control group was perfused with the buffer only. Calendula achieved cardioprotection by stimulating left ventricular developed pressure and aortic flow as well as by reducing myocardial infarct size and cardiomyocyte apoptosis. Cardioprotection appears to be achieved by changing ischemia reperfusion-mediated death signal into a survival signal by modulating antioxidant and anti-inflammatory pathways as evidenced by the activation of Akt and Bcl2 and depression of TNFα. The results further strengthen the concept of using natural products in degeneration diseases like ischemic heart disease.

  4. [Protective effects of SMT on myocardial ultrastructure of ischemia reperfusion injury in heart of rat].

    PubMed

    Zheng, H Z; Cai, B; Feng, Y H; Sun, H; Cai, K R

    2000-11-01

    To Investigate the myocardial ultrastructure effects of SMT on the ischemia reperfusion injury (IRI) in the rat heart. Eighteen Spraqua-Dawley rats were randomly divided into three groups: ischemia reperfusion group (IR), subjected to 60 min of o-cclusion and 20 min of reperfusion of the anterior descending branch of left coronary artery; IR + SMT group (SMT), given the selective iNOS inhibitor S-methylisothiourea sulfate (SMT, 5 mg/kg, i.v.) before reperfusion; control group (C), didn't occlude coronary artery after exposing heart and observed 80 min. Electrocardiogram (ECG) was recorded. Nitrite and nitrate content were measured in myocardium and blood serum. The changes of myocardial ultrastructure were observed with electron microscope. Ischemia reperfusion induced ST segment elevation and T waves inversion or tallness in ECG, damaged myocardial ultrastructure, increased nitrite and nitrate content in myocardium and blood serum after IR compared with before IR(P < 0.01). Administration of SMT improved the changes of ECG and the injury of myocardial ultrastructure. Nitrite and nitrate content of myocardium were lower than IR group (P < 0.05). The change of nitrite and nitrate level of blood serum in SMT group was nearly in C group. SMT can prevent myocardium injury from reperfusion following ischemia.

  5. Perflubron emulsion prevents PMN activation and improves myocardial functional recovery after cold ischemia and reperfusion.

    PubMed

    Gale, Stephen C; Gorman, Grace D; Copeland, Jack G; McDonagh, Paul F

    2007-03-01

    In cardiopulmonary bypass, extracorporeal circulation activates neutrophils, which contribute to ischemia reperfusion injury and postoperative myocardial dysfunction. Perfluorocarbons (PFCs) are compounds that dissolve oxygen and have anti-inflammatory and neutrophil-stabilizing properties. We hypothesized that perflubron emulsion (PFE), a PFC, would attenuate neutrophil activation during simulated extracorporeal circulation (SECC) and would preserve myocardial functional recovery during reperfusion after cold ischemia. In a SECC, diluted blood was circulated for 120 min and subsequently used to reperfuse isolated rat hearts after 2 h of cold (12 degrees C) ischemia. Three groups were studied: noncirculated control; SECC/no additive; and SECC/PFE added. In control and SECC/no additive groups, whole blood was diluted 1:1 with plasmalyte. SECC/PFE blood was diluted 1:1 with plasmalyte and PFE (0.075 mL/mL diluted whole blood). Blood counts and neutrophil activation experiments were performed before and after 120 min of SECC. Reperfusion was accomplished using a modified Langendorff preparation. Left ventricular developed pressure, dP/dt, and coronary flow were measured at 10, 15, and 20 min of reperfusion. After 120 min SECC, neutrophil activation was significantly reduced in the SECC/PFE group compared to the SECC/no additive group (38.1 +/- 2.3% versus 51.7 +/- 1.0%, P < 0.05). Compared to cold ischemic hearts reperfused with fresh, non-recirculated blood, left ventricular developed pressure and dP/dt were significantly impaired in the cold ischemic hearts reperfused with SECC/no additive blood (P < 0.05). In contrast, myocardial functional recovery was not impaired in the hearts reperfused with SECC/PFE blood. SECC-induced neutrophil activation was attenuated with Perflubron treatment. In addition, the progressive impairment in myocardial functional recovery after cold ischemia was significantly improved with treatment. PFE has clinical potential to limit

  6. Glaucocalyxin A Ameliorates Myocardial Ischemia-Reperfusion Injury in Mice by Suppression of Microvascular Thrombosis

    PubMed Central

    Liu, Xiaohui; Xu, Dongzhou; Wang, Yuxin; Chen, Ting; Wang, Qi; Zhang, Jian; You, Tao; Zhu, Li

    2016-01-01

    Background The aim of this study was to evaluate the cardio-protective roles of glaucocalyxin A (GLA) in myocardial ischemia-reperfusion injury and to explore the underlying mechanism. Material/Methods Myocardial ischemia-reperfusion in wild-type C57BL/6J mice was induced by transient ligation of the left anterior descending artery. GLA or vehicle (solvent) was administrated intraperitoneally to the mice before reperfusion started. After 24 h of myocardial reperfusion, ischemic size was revealed by Evans blue/TTC staining. Cardiac function was evaluated by echocardiography and microvascular thrombosis was assessed by immunofluorescence staining of affected heart tissue. We also measured the phosphorylation of AKT, ERK, P-GSK-3β, and cleaved caspase 3 in the myocardium. Results Compared to the solvent-treated control group, GLA administration significantly reduced infarct size (GLA 13.85±2.08% vs. Control 18.95±0.97%, p<0.05) and improved left ventricular ejection fraction (LVEF) (GLA 53.13±1.11% vs. Control 49.99±1.25%, p<0.05) and left ventricular fractional shortening (LVFS) (28.34±0.71% vs. Control 25.11±0.74%, p<0.05) in mice subjected to myocardial ischemia-reperfusion. GLA also attenuated microvascular thrombosis (P<0.05) and increased the phosphorylation of pro-survival kinase AKT (P<0.05) and GSK-3β (P<0.05) in the myocardium upon reperfusion injury. Conclusions Administration of GLA before reperfusion ameliorates myocardial ischemia-reperfusion injury in mice. The cardio-protective roles of GLA may be mediated through the attenuation of microvascular thrombosis. PMID:27716735

  7. Cardiomyocyte-specific overexpression of an active form of Rac predisposes the heart to increased myocardial stunning and ischemia-reperfusion injury

    PubMed Central

    Talukder, M. A. Hassan; Elnakish, Mohammad T.; Yang, Fuchun; Nishijima, Yoshinori; Alhaj, Mazin A.; Velayutham, Murugesan; Hassanain, Hamdy H.

    2013-01-01

    The GTP-binding protein Rac regulates diverse cellular functions including activation of NADPH oxidase, a major source of superoxide production (O2·−). Rac1-mediated NADPH oxidase activation is increased after myocardial infarction (MI) and heart failure both in animals and humans; however, the impact of increased myocardial Rac on impending ischemia-reperfusion (I/R) is unknown. A novel transgenic mouse model with cardiac-specific overexpression of constitutively active mutant form of Zea maize Rac D (ZmRacD) gene has been reported with increased myocardial Rac-GTPase activity and O2·− generation. The goal of the present study was to determine signaling pathways related to increased myocardial ZmRacD and to what extent hearts with increased ZmRacD proteins are susceptible to I/R injury. The effect of myocardial I/R was examined in young adult wild-type (WT) and ZmRacD transgenic (TG) mice. In vitro reversible myocardial I/R for postischemic cardiac function and in vivo regional myocardial I/R for MI were performed. Following 20-min global ischemia and 45-min reperfusion, postischemic cardiac contractile function and heart rate were significantly reduced in TG hearts compared with WT hearts. Importantly, acute regional myocardial I/R (30-min ischemia and 24-h reperfusion) caused significantly larger MI in TG mice compared with WT mice. Western blot analysis of cardiac homogenates revealed that increased myocardial ZmRacD gene expression is associated with concomitant increased levels of NADPH oxidase subunit gp91phox, O2·−, and P21-activated kinase. Thus these findings provide direct evidence that increased levels of active myocardial Rac renders the heart susceptible to increased postischemic contractile dysfunction and MI following acute I/R. PMID:23161879

  8. A Role for Photobiomodulation in the Prevention of Myocardial Ischemic Reperfusion Injury: A Systematic Review and Potential Molecular Mechanisms

    PubMed Central

    Liebert, Ann; Krause, Andrew; Goonetilleke, Neil; Bicknell, Brian; Kiat, Hosen

    2017-01-01

    Myocardial ischemia reperfusion injury is a negative pathophysiological event that may result in cardiac cell apoptosis and is a result of coronary revascularization and cardiac intervention procedures. The resulting loss of cardiomyocyte cells and the formation of scar tissue, leads to impaired heart function, a major prognostic determinant of long-term cardiac outcomes. Photobiomodulation is a novel cardiac intervention that has displayed therapeutic effects in reducing myocardial ischemia reperfusion related myocardial injury in animal models. A growing body of evidence supporting the use of photobiomodulation in myocardial infarct models has implicated multiple molecular interactions. A systematic review was conducted to identify the strength of the evidence for the therapeutic effect of photobiomodulation and to summarise the current evidence as to its mechanisms. Photobiomodulation in animal models showed consistently positive effects over a range of wavelengths and application parameters, with reductions in total infarct size (up to 76%), decreases in inflammation and scarring, and increases in tissue repair. Multiple molecular pathways were identified, including modulation of inflammatory cytokines, signalling molecules, transcription factors, enzymes and antioxidants. Current evidence regarding the use of photobiomodulation in acute and planned cardiac intervention is at an early stage but is sufficient to inform on clinical trials. PMID:28181487

  9. Guidelines for management of acute myocardial infarction.

    PubMed

    Banerjee, Amal Kumar; Kumar, Soumitra

    2011-12-01

    These Guidelines summarize and evaluate all currently available evidence on Acute Myocardial Infarction (AMI) with the aim of assisting physicians in selecting the best management strategies for a typical patient, suffering from AMI, taking into account the impact on outcome, as well as the risk/benefit ratio of particular diagnostic or therapeutic means. Rapid diagnosis and early risk stratification of patients presenting with AMI are important to identify patients in whom early interventions can improve outcome. AMI can be defined from a number of different perspectives related to clinical, electrocardiographic (ECG), biochemical, and pathological characteristics. Quantitative assessment of risk is useful for clinical decision making. For patients with the clinical presentation of AMI within 12 h after symptom onset, early mechanical (PCI) or pharmacological reperfusion should be performed. Platelet activation and subsequent aggregation play a dominant role in the propagation of arterial thrombosis and consequently are the key therapeutic targets in the management of AMI. Adjunctive therapy with antiplatelets and antithrombotics is essential. A recommendation for routine urgent PCI (within 24 h) following successful fibrinolysis seems to be most practical option. In India, pharmacoinvasive therapy is the best option.

  10. [Thrombolytic therapy of acute myocardial infarct].

    PubMed

    Murín, J; Kasper, J; Bulas, J; Uhliar, R

    1993-08-01

    In the period of two years the authors treated at the coronary care unit 146 patients inflicted by the acute myocardial infarction (AMI). In 15 of them (13 men, 2 women, 13 times Q and twice non-Q, 5 times anterior, 10 times inferior) they performed intravenous thrombolytic treatment by use of streptokinase. The success rate of the thrombolytic therapy was evaluated by noninvasive markers: 1.) rapid withdrawal of chest pain, 2.) rapid (in 6 hours) and essential improvement of ST segment elevation and 3.) presence of reperfusion arrhythmias (in 6 hours). The authors detected insufficient medicinal conciousness among their health district population as regard to their response after the AMI origin (absolute majority of patients delayed their arrival). Minor complications due to therapy (allergy and minor local hemorrhage) occurred in 4 patients. Nobody died. Only those cases were considered as being successful, in which all three success rate markers were present. This condition was fulfilled in 8 patients (i.e. in 53% of cases) and with minor insufficiencies in further two patients (which would increase the percentage of the success rate to 67%). This success rate of the thrombolytic therapy ranges within the limits given by literature. In five patients the authors evaluated the behaviour of the left ventricular asynergy (its range and index) prior to and following the thrombolytic therapy and this examination they consider to be appropriate for observance of the thrombolytic therapy success rate in patients with AMI. (Tab. 3, Ref. 20.).

  11. Assessment of inflammation with a very small iron-oxide particle in a murine model of reperfused myocardial infarction.

    PubMed

    Protti, Andrea; Dong, Xuebin; Andia, Marcelo E; Yu, Bin; Dokukina, Kate; Chaubey, Sanjay; Phinikaridou, Alkystis; Vizcay-Barrena, Gema; Taupitz, Matthias; Botnar, Rene M; Shah, Ajay M

    2014-03-01

    To investigate a very small iron-oxide particle (VSOP) in a mouse model of acute ischemia-reperfusion to access the mechanism of such particles in areas of myocardial inflammation. Animals were injected with VSOP at several time points, in a mouse model of acute myocardial infarction (MI), before and after MI. MRI was used to localize areas of VSOP enhancement, evaluate VSOP areas extension, and determine the related T2* values. Histology, electron microscopy, macrophage counting, and Evan's Blue staining were also performed. We found that areas of VSOP uptake decreased from 1 to 8 days post-MI while the related T2* values increased. T2* and VSOP areas, defined from MRI data, correlated well between 1 and 3 days post-MI but not at 7 days after injection. Histological analysis and electron microscopy showed colocalization of macrophages with areas of VSOP staining. However, there was no correlation between number of macrophages and the extension of the VSOP areas achieved by MR. We found that only areas of increased permeability (assessed by Evan's Blue staining) showed colocalization of macrophages and VSOP uptake. This study demonstrates that VSOP allows the assessment of myocardial inflammation associated with increased permeability during infarct healing in a mouse model of ischemia-reperfusion. Copyright © 2013 Wiley Periodicals, Inc.

  12. Therapeutic potential of sulindac against ischemia-reperfusion-induced myocardial infarction in diabetic and nondiabetic rats

    PubMed Central

    Annapurna, Akula; Challa, Siva Reddy; Prakash, Gomedhikam J; Viswanath, Routhu Kasi

    2008-01-01

    BACKGROUND Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state. OBJECTIVES To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats. METHODS Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically. RESULTS Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats. CONCLUSIONS The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac. PMID:19343118

  13. Therapeutic potential of sulindac against ischemia-reperfusion-induced myocardial infarction in diabetic and nondiabetic rats.

    PubMed

    Annapurna, Akula; Challa, Siva Reddy; Prakash, Gomedhikam J; Viswanath, Routhu Kasi

    2008-01-01

    Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state. To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats. Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically. Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats. The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac.

  14. Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart.

    PubMed Central

    Bani, D.; Masini, E.; Bello, M. G.; Bigazzi, M.; Sacchi, T. B.

    1998-01-01

    Myocardial injury caused by ischemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, platelet and mast cell activation, and peroxidation of cell membrane lipids, which are followed by myocardial cell alterations resulting eventually in cell necrosis. The current study was designed to test the possible cardioprotective effect of the hormone relaxin, which has been found to cause coronary vessel dilation and to inhibit platelet and mast cell activation. Ischemia (for 30 minutes) was induced in rat hearts in vivo by ligature of the left anterior descending coronary artery; reperfusion (for 60 minutes or less if the rats died before this predetermined time) was induced by removal of the ligature. Relaxin (100 ng) was given intravenously 30 minutes before ischemia. The results obtained showed that relaxin strongly reduces 1) the extension of the myocardial areas affected by ischemia-reperfusion-induced damage, 2) ventricular arrhythmias, 3) mortality, 4) myocardial neutrophil number, 5) myeloperoxidase activity, a marker of neutrophil accumulation, 6) production of malonyldialdehyde, an end product of lipid peroxidation, 7) mast cell granule release, 8) calcium overload, and 9) morphological signs of myocardial cell injury. This study shows that relaxin can be regarded as an agent with a marked cardioprotective action against ischemia-reperfusion-induced myocardial injury. Images Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:9588905

  15. Comparison between primary angioplasty and thrombolytic therapy on erectile dysfunction after acute ST elevation myocardial infarction

    PubMed Central

    Akdemir, Ramazan; Karakurt, Özlem; Orcan, Salih; Karakoyunlu, Nihat; Mucahit Balci, Mustafa; Sağnak, Levent; Ersoy, Hamit; Bulent Vatan, Mehmet; Kilic, Harun; Yeter, Ekrem

    2012-01-01

    Acute ST elevation myocardial infarction has high mortality and morbidity rates. The majority of patients with this condition face erectile dysfunction in addition to other health problems. In this study, we aimed to investigate the effects of two different reperfusion strategies, primary angioplasty and thrombolytic therapy, on the prevalence of erectile dysfunction after acute myocardial infarction. Of the 71 patients matching the selection criteria, 45 were treated with primary coronary angioplasty with stenting, and 26 were treated with thrombolytic agents. Erectile function was evaluated using the International Index of Erectile Function in the hospital to characterize each patient's sexual function before the acute myocardial infarction and 6 months after the event. The time required to restore blood flow to the artery affected by the infarct was found to be associated with the occurrence of erectile dysfunction after acute myocardial infarction. The increase in the prevalence of erectile dysfunction after acute myocardial infarction was 44.4% in the angioplasty group and 76.9% in the thrombolytic therapy group (P=0.008). In conclusion, this study has shown that reducing the time of reperfusion decreases the erectile dysfunction prevalence, and primary angioplasty is superior to thrombolytic therapy for decreasing the prevalence of erectile dysfunction after acute myocardial infarction. PMID:22796737

  16. Reperfusion therapy of myocardial infarction in Mexico: A challenge for modern cardiology.

    PubMed

    Martínez-Sánchez, Carlos; Arias-Mendoza, Alexandra; González-Pacheco, Héctor; Araiza-Garaygordobil, Diego; Marroquín-Donday, Luis Alfonso; Padilla-Ibarra, Jorge; Sierra-Fernández, Carlos; Altamirano-Castillo, Alfredo; Álvarez-Sangabriel, Amada; Azar-Manzur, Francisco Javier; Briseño-de la Cruz, José Luis; Mendoza-García, Salvador; Piña-Reyna, Yigal; Martínez-Ríos, Marco Antonio

    Mexico has been positioned as the country with the highest mortality attributed to myocardial infarction among the members of the Organization for Economic Cooperation and Development. This rate responds to multiple factors, including a low rate of reperfusion therapy and the absence of a coordinated system of care. Primary angioplasty is the reperfusion method recommended by the guidelines, but requires multiple conditions that are not reached at all times. Early pharmacological reperfusion of the culprit coronary artery and early coronary angiography (pharmacoinvasive strategy) can be the solution to the logistical problem that primary angioplasty rises. Several studies have demonstrated pharmacoinvasive strategy as effective and safe as primary angioplasty ST-elevation myocardial infarction, which is postulated as the choice to follow in communities where access to PPCI is limited. The Mexico City Government together with the National Institute of Cardiology have developed a pharmaco-invasive reperfusion treatment program to ensure effective and timely reperfusion in STEMI. The model comprises a network of care at all three levels of health, including a system for early pharmacological reperfusion in primary care centers, a digital telemedicine system, an inter-hospital transport network to ensure primary angioplasty or early percutaneous coronary intervention after fibrinolysis and a training program with certification of the health care personal. This program intends to reduce morbidity and mortality associated with myocardial infarction. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  17. Relationship of plasma neuropeptide Y with angiographic, electrocardiographic and coronary physiology indices of reperfusion during ST elevation myocardial infarction

    PubMed Central

    Cuculi, Florim; Herring, Neil; De Caterina, Alberto R; Banning, Adrian P; Prendergast, Bernard D; Forfar, John C; Choudhury, Robin P; Channon, Keith M; Kharbanda, Rajesh K

    2016-01-01

    Objectives The co-transmitter neuropeptide Y (NPY) is released during high levels of sympathetic stimulation and is a potent vasoconstrictor. We defined the release profile of plasma NPY during acute ST elevation myocardial infarction, and tested the hypothesis that levels correlate with reperfusion measures after treatment with primary percutaneous coronary intervention (PPCI). Design Prospective observational study. Setting University hospital heart centre. Patients 64 patients (62.6±11.7 years-old, 73% male) presenting throughout the 24-h cycle of clinical activity with ST elevation myocardial infarction. Interventions PPCI. Main outcome measures NPY was measured (ELISA) in peripheral blood taken before and immediately after PPCI and at 6, 24 and 48 h post-PPCI. Reperfusion was assessed by angiographic criteria, ST segment resolution, invasive measurement of coronary flow reserve and the index of microcirculatory resistance. Results Plasma NPY levels were highest before PPCI (17.4 (8.8–42.2) pg/ml, median (IQR)) and dropped significantly post-PPCI (12.4 (6.5–26.7) pg/ml, p<0.0001) and after 6 h (9.0 (2.6–21.5) pg/ml, p=0.008). Patients with admission NPY levels above the median were significantly more hypertensive and tachycardic and were more likely to have diabetes mellitus. Patients with angiographic no-reflow (less than thrombolysis in myocardial infarction 3 flow and myocardial blush grade >2, n=16) or no electrocardiographic ST resolution (<70%, n=30) following PPCI had significantly higher plasma NPY levels. Patients with a coronary flow reserve <1.5 or index of microcirculatory resistance >33 also had significantly higher plasma NPY levels pre-PPCI and post-PPCI. Conclusions Plasma NPY levels correlate with indices of reperfusion and coronary microvascular resistance. PMID:23403409

  18. Relationship of plasma neuropeptide Y with angiographic, electrocardiographic and coronary physiology indices of reperfusion during ST elevation myocardial infarction.

    PubMed

    Cuculi, Florim; Herring, Neil; De Caterina, Alberto R; Banning, Adrian P; Prendergast, Bernard D; Forfar, John C; Choudhury, Robin P; Channon, Keith M; Kharbanda, Rajesh K

    2013-08-01

    The co-transmitter neuropeptide Y (NPY) is released during high levels of sympathetic stimulation and is a potent vasoconstrictor. We defined the release profile of plasma NPY during acute ST elevation myocardial infarction, and tested the hypothesis that levels correlate with reperfusion measures after treatment with primary percutaneous coronary intervention (PPCI). Prospective observational study. University hospital heart centre. 64 patients (62.6±11.7 years-old, 73% male) presenting throughout the 24-h cycle of clinical activity with ST elevation myocardial infarction. PPCI. NPY was measured (ELISA) in peripheral blood taken before and immediately after PPCI and at 6, 24 and 48 h post-PPCI. Reperfusion was assessed by angiographic criteria, ST segment resolution, invasive measurement of coronary flow reserve and the index of microcirculatory resistance. Plasma NPY levels were highest before PPCI (17.4 (8.8-42.2) pg/ml, median (IQR)) and dropped significantly post-PPCI (12.4 (6.5-26.7) pg/ml, p<0.0001) and after 6 h (9.0 (2.6-21.5) pg/ml, p=0.008). Patients with admission NPY levels above the median were significantly more hypertensive and tachycardic and were more likely to have diabetes mellitus. Patients with angiographic no-reflow (less than thrombolysis in myocardial infarction 3 flow and myocardial blush grade >2, n=16) or no electrocardiographic ST resolution (<70%, n=30) following PPCI had significantly higher plasma NPY levels. Patients with a coronary flow reserve <1.5 or index of microcirculatory resistance >33 also had significantly higher plasma NPY levels pre-PPCI and post-PPCI. Plasma NPY levels correlate with indices of reperfusion and coronary microvascular resistance.

  19. Attenuation of interleukin-8 expression in C6-deficient rabbits after myocardial ischemia/reperfusion.

    PubMed

    Kilgore, K S; Park, J L; Tanhehco, E J; Booth, E A; Marks, R M; Lucchesi, B R

    1998-01-01

    Neutrophil accumulation and activation of the complement system with subsequent deposition of the cytolytic membrane attack complex (MAC) have been implicated in the pathogenesis of myocardial ischemia/reperfusion injury. The MAC, when present in high concentrations, promotes target cell lysis. However, relatively little is known about the potential modulatory role of sublytic concentrations of the MAC on nucleated cell function in vivo. In vitro studies demonstrated that the MAC regulates cell function by promoting the expression of pro-inflammatory mediators, including adhesion molecules and pro-inflammatory cytokines. We examined, using C6-deficient and C6-sufficient rabbits, the regulatory role of the MAC in mediating IL-8 expression and subsequent neutrophil recruitment in the setting of myocardial ischemia/reperfusion injury. C6-deficient and C6-sufficient rabbits were subjected to 30 min of regional myocardial ischemia followed by a period of reperfusion. In addition to a significant reduction in myocardial infarct size in C6-deficient animals, analysis of myocardial tissue demonstrated a decrease in neutrophil influx into the infarcted region. The reduction in neutrophil influx correlated with the decreased expression of the neutrophil chemotactic cytokine IL-8, as determined by ELISA and immunohistochemical analysis. The results derived from this study provide evidence that the MAC has an important function in mediating the recruitment of neutrophils to the reperfused myocardium through the local induction of IL-8.

  20. Neutrophil accumulation in experimental myocardial infarcts: relation with extent of injury and effect of reperfusion

    SciTech Connect

    Chatelain, P.; Latour, J.G.; Tran, D.; de Lorgeril, M.; Dupras, G.; Bourassa, M.

    1987-05-01

    The effects of reperfusion on the myocardial accumulation of neutrophils and their role in the extent of injury were investigated in a canine preparation with a 3 hr coronary occlusion followed by 21 hr of reperfusion. The left anterior descending coronary artery (LAD) was permanently occluded in group 1 and reperfused after 3 hr in four others (groups 2 to 5). All but group 5 received lidocaine (1 mg/min over 8 hr). A critical stenosis was produced and left in place at reperfusion only in group 2. In groups 1 and 2, /sup 111/In-labeled autologous neutrophils were injected at the time of coronary occlusion. Group 4 animals were rendered leukopenic 2 hr before the coronary ligature and throughout the experiment by injection of an antineutrophil rabbit serum. Quantification of the radioactivity by digitized scintigraphy of the heart slices revealed an 80% increase in neutrophil accumulation in the infarct region after reperfusion (group 2) as compared with permanent occlusion (group 1). Gamma counting of myocardial tissue samples showed that the neutrophil accumulation ratio in the subendocardial central zone of the infarct was increased five times by reperfusion, whereas no difference was evident in the subepicardium. Infarct size and myocardial area at risk were not statistically different among the five groups. However LAD flow in the leukopenic group (group 4) was significantly higher 30 min after reperfusion (40.0 +/- 5 ml/min) when compared with the preocclusion value (21.7 +/- 4 ml/min). In contrast, in a parallel experiment without leukopenia (group 3), LAD flow after reperfusion did not differ from the preocclusion value.

  1. A review of strategies for infarct size reduction during acute myocardial infarction.

    PubMed

    Parviz, Yasir; Vijayan, Sethumadhavan; Lavi, Shahar

    2017-02-08

    Advances in medical and interventional therapy over the last few decades have revolutionized the treatment of acute myocardial infarction. Despite the ability to restore epicardial coronary artery patency promptly through percutaneous coronary intervention, tissue level damage may continue. The reported 30-day mortality after all acute coronary syndromes is 2 to 3%, and around 5% following myocardial infarction. Post-infarct complications such as heart failure continue to be a major contributor to cardiovascular morbidity and mortality. Inadequate microvascular reperfusion leads to worse clinical outcomes and potentially strategies to reduce infarct size during periods of ischemia-reperfusion can improve outcomes. Many strategies have been tested, but no single strategy alone has shown a consistent result or benefit in large scale randomised clinical trials. Herein, we review the historical efforts, current strategies, and potential novel concepts that may improve myocardial protection and reduce infarct size.

  2. Effect of reperfusion and hyperemia on the myocardial distribution of technetium-99m t-butylisonitrile

    SciTech Connect

    Holman, B.L.; Campbell, C.A.; Lister-James, J.; Jones, A.G.; Davison, A.; Kloner, R.A.

    1986-07-01

    Technetium-99m t-butylisonitrile ((/sup 99m/Tc)TBI) is a promising new radiotracer for myocardial imaging. Its myocardial uptake is sufficiently high in humans to permit planar, tomographic, and gated images of excellent technical quality. We studied the behavior of (/sup 99m/Tc)TBI in the dog at rest and under conditions of hyperemia and reperfusion in order to determine the relationship between (/sup 99m/Tc)TBI myocardial concentration and blood flow. After permanent occlusion of the left anterior descending artery, the correlation between the relative myocardial concentration of (/sup 99m/Tc)TBI and regional myocardial blood flow (RMBF) measured with radiolabeled microspheres was excellent. In a dog model of transient hyperemia, the concentration of (/sup 99m/Tc)TBI was directly related to blood flow but underestimated the degree of hyperemia. Technetium-99m TBI redistributed into transiently ischemic myocardium. The myocardial concentrations of (/sup 99m/Tc)TBI and thallium-201(/sup 201/TI) in transiently ischemic myocardium were similar at 10 and 30 min following reperfusion and were significantly higher than blood flow prior to reperfusion. When (/sup 99m/Tc)TBI was injected into the left anterior descending artery, the washout was slow, falling to 78% of initial activity at 120 min after injection. In conclusion, (/sup 99m/Tc)TBI reflects regional myocardial blood flow accurately in ischemic and normal resting myocardium and underestimates blood flow at high flows. The rate of myocardial redistribution after reperfusion is similar for (/sup 99m/Tc)TBI and /sup 201/TI.

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. Protective role of intracellular zinc in myocardial ischemia/reperfusion is associated with preservation of protein kinase C isoforms.

    PubMed

    Karagulova, Gulnura; Yue, Yuankun; Moreyra, Abel; Boutjdir, Mohamed; Korichneva, Irina

    2007-05-01

    The recent discovery of zinc signals and their essential role in the redox signaling network implies that zinc homeostasis and the function of zinc-containing proteins are probably altered as a result of oxidative stress, suggesting new targets for pharmacological intervention. We hypothesized that the level of intracellular labile zinc is changed in hearts subjected to ischemia/reperfusion (I/R) and investigated whether the maintenance of myocardial zinc status protected heart functions. Using fluorescent imaging, we demonstrated decreased levels of labile zinc in the I/R hearts. Phorbol 12-myristate 13-acetate, a known trigger of zinc release, liberated zinc ions in control hearts but failed to produce any increase in zinc levels in the I/R rat hearts. Adding the zinc ionophore pyrithione at reperfusion improved myocardial recovery up to 100% and reduced the incidence of arrhythmias more than 2-fold. This effect was dose-dependent, and high concentrations of zinc were toxic. Adding membrane-impermeable zinc chloride was ineffective. Hearts from rats receiving zinc pyrithione supplements in their diet fully recovered from I/R. The recovery was associated with the prevention of degradation of the two protein kinase C isoforms, delta and epsilon, during I/R. In conclusion, our results suggest a protective role of intracellular zinc in myocardial recovery from oxidative stress imposed by I/R. The data support the potential clinical use of zinc ionophores in the settings of acute redox stress in the heart.

  6. Acute hypoxia-reperfusion triggers immunocompromise in Nile tilapia.

    PubMed

    Choi, K; Lehmann, D W; Harms, C A; Law, J M

    2007-06-01

    Inadequate dissolved oxygen in the aquatic environment is a well-established cause of fish morbidity and mortality. The specific effects of hypoxia on immune function in fish, however, are not well characterized. In this study, the effects of acute hypoxia followed by reoxygenation (rapid tissue reperfusion) as a source of immunocompromise in Nile tilapia Oreochromis niloticus were investigated. Using a precision apparatus developed in our laboratory for hypoxia exposures, a series of assays of increasing specificity for immune function were performed on acutely hypoxia-stressed Nile tilapia: tier I consisted of histopathology, tier II of hematology, plasma chemistry, and determining cortisol concentration, and tier III of determining the phagocytic index and analyzing the expression of the cytokines transforming growth factor-beta (TGF-beta) and interleukin-1beta (IL-1beta). Nile tilapia were exposed to 7% oxygen saturation for 96 h, then tank water was rapidly reoxygenated. Sampling intervals were 48 and 96 h during hypoxia and 12 and 84 h during reperfusion. Histopathology showed no remarkable microscopic abnormalities in lymphoid or other tissues. Lymphopenia and neutrophilia were observed in peripheral blood. Plasma total protein, partial pressure of oxygen, and oxygen saturation were decreased in response to hypoxia. Plasma lipase decreased in response to hypoxia but returned to normal during reperfusion. Phagocytic capability and the phagocytic index decreased during hypoxia and 12 h reperfusion, whereas these values were recovered by 84 h reperfusion. The TGF-beta transcription continued to increase during the exposures, the greatest production being at 12 h reperfusion, whereas IL-1beta transcription decreased in response to hypoxia and reperfusion. We conclude that acute hypoxia triggered an overall downregulation of the immune system in the test fish. This suggests a possible factor in the pathogenesis of disease outbreaks in fish in which repeated

  7. Acute Myocardial Infarction Quality of Care: The Strong Heart Study

    PubMed Central

    Best, Lyle G.; Butt, Amir; Conroy, Britt; Devereux, Richard B.; Galloway, James M.; Jolly, Stacey; Lee, Elisa T.; Silverman, Angela; Yeh, Jeun-Liang; Welty, Thomas K.; Kedan, Ilan

    2014-01-01

    Objectives Evaluate the quality of care provided patients with acute myocardial infarction and compare with similar national and regional data. Design Case series. Setting The Strong Heart Study has extensive population-based data related to cardiovascular events among American Indians living in three rural regions of the United States. Participants Acute myocardial infarction cases (72) occurring between 1/1/2001 and 12/31/2006 were identified from a cohort of 4549 participants. Outcome measures The proportion of cases that were provided standard quality of care therapy, as defined by the Healthcare Financing Administration and other national organizations. Results The provision of quality services, such as administration of aspirin on admission and at discharge, reperfusion therapy within 24 hours, prescription of beta blocker medication at discharge, and smoking cessation counseling were found to be 94%, 91%, 92%, 86% and 71%, respectively. The unadjusted, 30 day mortality rate was 17%. Conclusion Despite considerable challenges posed by geographic isolation and small facilities, process measures of the quality of acute myocardial infarction care for participants in this American Indian cohort were comparable to that reported for Medicare beneficiaries nationally and within the resident states of this cohort. PMID:21942161

  8. Edema is a sign of early acute myocardial infarction on post-mortem magnetic resonance imaging.

    PubMed

    Ruder, Thomas D; Ebert, Lars C; Khattab, Ahmed A; Rieben, Robert; Thali, Michael J; Kamat, Pranitha

    2013-12-01

    The aim of this study was to investigate if acute myocardial infarction can be detected by post-mortem cardiac magnetic resonance (PMMR) at an earlier stage than by traditional autopsy, i.e., within less than 4 h after onset of ischemia; and if so, to determine the characteristics of PMMR findings in early acute infarcts. Twenty-one ex vivo porcine hearts with acute myocardial infarction underwent T2-weighted cardiac PMMR imaging within 3 h of onset of iatrogenic ischemia. PMMR imaging findings were compared to macroscopic findings. Myocardial edema induced by ischemia and reperfusion was visible on PMMR in all cases. Typical findings of early acute ischemic injury on PMMR consist of a central zone of intermediate signal intensity bordered by a rim of increased signal intensity. Myocardial edema can be detected on cardiac PMMR within the first 3 h after the onset of ischemia in porcine hearts. The size of myocardial edema reflects the area of ischemic injury in early acute (per-acute) myocardial infarction. This study provides evidence that cardiac PMMR is able to detect acute myocardial infarcts at an earlier stage than traditional autopsy and routine histology.

  9. Human recombinant relaxin reduces heart injury and improves ventricular performance in a swine model of acute myocardial infarction.

    PubMed

    Perna, Avio-Maria; Masini, Emanuela; Nistri, Silvia; Bani Sacchi, Tatiana; Bigazzi, Mario; Bani, Daniele

    2005-05-01

    This study shows that relaxin can be effective in the treatment of acute myocardial infarction. In a swine model of heart ischemia-reperfusion currently used to test cardiotropic drugs because of its similarities with human myocardial infarction, human recombinant relaxin (2.5 and 5 microg/kg body weight), given at reperfusion after a 30-min ischemia, markedly reduced the main serum markers of myocardial damage (myoglobin, CK-MB, and troponin T) and the metabolic and histopathologic parameters of myocardial inflammation and cardiomyocyte injury, resulting in overall improvement of ventricular performance (increased cardiac index) compared to the controls. These results provide a background for future clinical trials with human relaxin as adjunctive therapy to catheter-based coronary angioplasty in patients with acute myocardial infarction.

  10. [Antioxidant and cardioprotective effects of N-tyrosol in myocardial ischemia with reperfusion in rats].

    PubMed

    Smol'iakova, V I; Chernyshova, G A; Plotnikov, M B; Aliev, O I; Krasnov, E A

    2010-01-01

    We demonstrated in experiments on rats with left coronary artery occlusion that intravenous administration of 20 mg/kg n-tyrosol during ischemia limited manifestations of oxidative stress in myocardial tissue during early post reperfusion period: content of diene and triene conjugates lowered 16 and 20%, respectively. This was associated with higher preservation of cardiomyocytes and reduction of the infarction zone.

  11. Endotoxin pretreatment increases endogenous myocardial catalase activity and decreases ischemia-reperfusion injury of isolated rat hearts.

    PubMed Central

    Brown, J M; Grosso, M A; Terada, L S; Whitman, G J; Banerjee, A; White, C W; Harken, A H; Repine, J E

    1989-01-01

    Hearts isolated from rats pretreated 24 hr before with endotoxin had increased myocardial catalase activity, but the same superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities, as hearts from untreated rats. Hearts isolated from rats pretreated with endotoxin 24 hr before also had increased myocardial function (decreased injury) after ischemia and reperfusion (Langendorff apparatus, 37 degrees C), as assessed by measurement of ventricular developed pressure, contractility (+dP/dt), and relaxation rate (-dP/dt), compared to control hearts. In contrast, hearts isolated from rats pretreated with endotoxin 1 hr before isolation or hearts perfused with endotoxin did not have increased catalase activity or decreased injury following ischemia and reperfusion. Aminotriazole pretreatment prevented increases in myocardial catalase activity and myocardial function after ischemia-reperfusion in hearts from endotoxin-pretreated rats. The results suggest that endotoxin pretreatment decreases cardiac ischemia-reperfusion injury and that increases in endogenous myocardial catalase activity contribute to protection. PMID:2648406

  12. Quantitative T2 mapping for detecting myocardial edema after reperfusion of myocardial infarction: validation and comparison with T2-weighted images.

    PubMed

    Park, Chul Hwan; Choi, Eui-Young; Kwon, Hyuck Moon; Hong, Bum Kee; Lee, Byoung Kwon; Yoon, Young Won; Min, Pil-Ki; Greiser, Andreas; Paek, Mun Young; Yu, Wei; Sung, Yon Mi; Hwang, Sung Ho; Hong, Yoo Jin; Kim, Tae Hoon

    2013-06-01

    This study evaluates the clinical usefulness of T2 mapping for the detection of myocardial edema in the re-perfused acute myocardial infarction (MI). Cardiac MRIs were reviewed in 20 patients who had acute MI after reperfusion therapy. The regional T2 values and T2-weighted image (T2WI) signal intensities (SI) were measured in the infarcted and remote zones of the myocardium. Patients were divided into three groups according to the signal patterns of the infarcted myocardium on the T2WIs. The T2 values of the infarcted zones were compared on the T2 maps among the three groups. Validation of the T2 values was performed in the normal myocardium of seven healthy volunteers. There were no significant differences in mean T2WI-SI or T2 values in the normal myocardium of healthy volunteers compared to the remote myocardium of acute MI patients (p > 0.05). Mean SI on the T2WIs was significantly higher in the infarcted myocardium (81.3 ± 37.6) than in the remote myocardium (63.8 ± 18.1) (p < 0.05). The T2WIs showed high SI in ten patients (group 1), iso-SI in seven (group 2), and low SI in three (group 3) in the infarcted myocardium, compared to the remote myocardium. The T2 maps showed that T2 values in the infarcted myocardium had mostly increased, regardless of group, with values of 71 ± 9 ms in group 1, 64.9 ± 7.4 ms in group 2, and 61.4 ± 8.5 ms in group 3. T2 mapping is superior to T2WI for detecting areas of high SI in the infarcted myocardium. Therefore, quantitative T2 mapping sequences may be more useful and reliable in identifying myocardial edema in the infarcted myocardium than T2WI.

  13. Cardioprotective effects of bosentan, a mixed endothelin type A and B receptor antagonist, during myocardial ischaemia and reperfusion in rats.

    PubMed

    Singh, Arya Dharamvir; Amit, Saxena; Kumar, Ojha Shreesh; Rajan, Mittal; Mukesh, Nandave

    2006-06-01

    The present study evaluated the cardioprotective potential of bosentan, a mixed endothelin type A and B receptor antagonist, in the myocardial ischaemia-reperfusion model of myocardial infarction. Adult male wistar rats (175-225 g) were divided into three groups: sham operated, non-myocardial ischaemia-reperfusion (SHAM); saline-treated myocardial ischaemia-reperfusion control (CON); bosentan-treated myocardial ischaemia-reperfusion (BOS). All animals were anaesthetized and subjected to 40 min. occlusion of left anterior descending coronary artery followed by 120 min. of reperfusion. Saline or drug was administered to the CON or BOS group, respectively, 20 min. after the left anterior descending coronary artery occlusion. Haemodynamic parameters viz. systolic arterial pressure, diastolic arterial pressure and heart rate were recorded throughout the experimental period. Hearts were subsequently excised and processed for histopathological and infarct size evaluation and for biochemical estimation of cardiac specific enzyme creatine kinase-MB (CK-MB) and myocardial malondialdehyde, a lipid peroxidation marker. Myocardial ischaemic reperfusion resulted in severe myocardial injury, depression of haemodynamic function, significant increase in malondialdehyde levels and decline in CK-MB isoenzyme activity in the heart tissue. Administration of bosentan (3 mg/kg, intravenously) slightly improved haemodynamic effects, decreased myocardial oxygen consumption, significantly (P<0.01) attenuated the rise in malondialdehyde levels and loss of myocardial CK-MB isoenzyme activity compared to the CON group, whereas bosentan administration significantly reduced the percentage area of fiber loss and infarct area. It is therefore concluded that endothelin-1 may mediate myocardial damage produced by ischaemia and reperfusion and that dual blockade of endothelinA and endothelinB receptors may have potential as a mode of therapy for myocardial infarction.

  14. Salidroside attenuates myocardial ischemia-reperfusion injury via PI3K/Akt signaling pathway.

    PubMed

    Xu, Mao-Chun; Shi, Hai-Ming; Gao, Xiu-Fang; Wang, Hao

    2013-01-01

    To investigate the cardioprotective effects of salidroside on myocardial ischemia-reperfusion injury (IRI) in rabbits and the underlying action mechanisms in PI3K/Akt signaling pathway, a rabbit ischemia/reperfusion model was created by ligating the left anterior descending coronary arterial branch for 30 min and by releasing the ligature to allow reperfusion for 120 min. Salidroside or salidroside+PI3K inhibitor (LY294002) was administered via intracoronary injections at the onset of reperfusion. Apoptosis of cardiomyocytes was assessed by terminal dUTP nick-end labeling assay, and the expression of apoptosis-related proteins was observed by immunohistochemistry. The expressions of total Akt and phosphorylated Akt (p-Akt) were detected by western blot analysis. The results showed that intracoronary injection of salidroside at the onset of reperfusion markedly reduced the apoptosis of cardiomyocytes, significantly increasing Bcl-2 and p-Akt proteins expressions and decreasing Bax and caspase-3 expressions in the hearts subjected to ischemia followed by 120-min reperfusion. However, the anti-apoptotic effect induced by salidroside was inhibited by LY294002, which blocked the activation of Akt. These results suggested that intracoronary administration of salidroside at the onset of reperfusion could significantly reduce the IRI-induced apoptosis of cardiomyocytes, and this protective mechanism seemed to be mediated by the PI3K-Akt signaling pathway.

  15. Comparative antiapoptotic effects of KB-R7943 and ischemic postconditioning during myocardial ischemia reperfusion.

    PubMed

    Ren, Yongkui; Cai, Yunfei; Jia, Dalin

    2012-11-01

    We examined whether KB-R7943 reduced infarct size by attenuating apoptosis during reperfusion and also compared antiapoptotic effects of KB-R7943 and IPost. For this purpose, isolated rat hearts underwent 30-min global ischemia and 120-min reperfusion. Ischemic postconditioning (IPost) (n = 15; three cycles of 10-s reperfusion/10-s ischemia or three cycles of 30-s reperfusion/30-s ischemia) and KB-R7943 (n = 15; 1 μM KB-R at the onset of reperfusion or before ischemia) were compared with controls (n = 12; ischemia-reperfusion only). Myocardial injury was determined by TTC staining, TUNEL assay and caspase-3 activity. AKT and eNOS phosphorylation were measured by immunoblotting. We found that IPost (10 s), Pre KB-R, and Reperf KB-R reduced infarct size (29 ± 4.1, 35 ± 5.0, 28.6 ± 3.4 %, respectively, vs. controls 46 ± 8.7 %; P < 0.05) and attenuated cell apoptosis (TUNEL-positive cardiomyocyte nuclei) in the myocardium (P < 0.01). Moreover, IPost (10 s), Pre KB-R and Reperf KB-R significantly decreased caspase-3 activation caused by myocardial ischemia-reperfusion. However, IPost (30 s) did not show any effect on necrosis and apoptosis. Akt, eNOS phosphorylation, at 30 min of reperfusion/IPost-10 s was significantly higher than other groups. In conclusion, KB-R7943 was as effective as IPost in reducing necrosis and inhibiting apoptosis and it might be an ideal pharmacological agent to provide a more amenable approach to cardioprotection.

  16. Renal oxygenation in acute renal ischemia-reperfusion injury.

    PubMed

    Abdelkader, Amany; Ho, Julie; Ow, Connie P C; Eppel, Gabriela A; Rajapakse, Niwanthi W; Schlaich, Markus P; Evans, Roger G

    2014-05-01

    Tissue hypoxia has been demonstrated, in both the renal cortex and medulla, during the acute phase of reperfusion after ischemia induced by occlusion of the aorta upstream from the kidney. However, there are also recent clinical observations indicating relatively well preserved oxygenation in the nonfunctional transplanted kidney. To test whether severe acute kidney injury can occur in the absence of widespread renal tissue hypoxia, we measured cortical and inner medullary tissue Po2 as well as total renal O2 delivery (Do2) and O2 consumption (Vo2) during the first 2 h of reperfusion after 60 min of occlusion of the renal artery in anesthetized rats. To perform this experiment, we used a new method for measuring kidney Do2 and Vo2 that relies on implantation of fluorescence optodes in the femoral artery and renal vein. We were unable to detect reductions in renal cortical or inner medullary tissue Po2 during reperfusion after ischemia localized to the kidney. This is likely explained by the observation that Vo2 (-57%) was reduced by at least as much as Do2 (-45%), due to a large reduction in glomerular filtration (-94%). However, localized tissue hypoxia, as evidence by pimonidazole adduct immunohistochemistry, was detected in kidneys subjected to ischemia and reperfusion, particularly in, but not exclusive to, the outer medulla. Thus, cellular hypoxia, particularly in the outer medulla, may still be present during reperfusion even when reductions in tissue Po2 are not detected in the cortex or inner medulla.

  17. Cyclosporin variably and inconsistently reduces infarct size in experimental models of reperfused myocardial infarction: a systematic review and meta-analysis

    PubMed Central

    Lim, WY; Messow, CM; Berry, C

    2012-01-01

    Cyclosporin is an immunosuppressant that has recently been proposed as a treatment to prevent reperfusion injury in acute myocardial infarction (MI). We aimed to determine the overall efficacy of cyclosporin in experimental studies of acute reperfused MI. We conducted a systematic review and stratified meta-analysis of published studies describing the efficacy of cyclosporin in experimental models of acute reperfused MI. We included all in vivo publications of cyclosporin where infarct size was measured. A literature search identified 29 potential studies of which 20 fulfilled the eligibility criteria. In these studies (involving four species of animals), cyclosporin reduced myocardial infarct size by a standardized mean (95% confidence interval) difference of −1.60 (−2.17, −1.03) compared with controls. Cyclosporin failed to demonstrate a convincing benefit in studies involving pigs. Despite this observation, the overall efficacy of cyclosporin did not differ across species (P= 0.358). The dose of cyclosporin given did not affect final infarct size (P= 0.203). Funnel plots of these data suggested heterogeneity among the studies. Cyclosporin had variable effects on infarct size compared with placebo. Cyclosporin had no effect on myocardial infarct size in swine, raising a question over the potential cardioprotective effects of cyclosporin in man. PMID:21950961

  18. Cyclosporin variably and inconsistently reduces infarct size in experimental models of reperfused myocardial infarction: a systematic review and meta-analysis.

    PubMed

    Lim, W Y; Messow, C M; Berry, C

    2012-04-01

    Cyclosporin is an immunosuppressant that has recently been proposed as a treatment to prevent reperfusion injury in acute myocardial infarction (MI). We aimed to determine the overall efficacy of cyclosporin in experimental studies of acute reperfused MI. We conducted a systematic review and stratified meta-analysis of published studies describing the efficacy of cyclosporin in experimental models of acute reperfused MI. We included all in vivo publications of cyclosporin where infarct size was measured. A literature search identified 29 potential studies of which 20 fulfilled the eligibility criteria. In these studies (involving four species of animals), cyclosporin reduced myocardial infarct size by a standardized mean (95% confidence interval) difference of -1.60 (-2.17, -1.03) compared with controls. Cyclosporin failed to demonstrate a convincing benefit in studies involving pigs. Despite this observation, the overall efficacy of cyclosporin did not differ across species (P= 0.358). The dose of cyclosporin given did not affect final infarct size (P= 0.203). Funnel plots of these data suggested heterogeneity among the studies. Cyclosporin had variable effects on infarct size compared with placebo. Cyclosporin had no effect on myocardial infarct size in swine, raising a question over the potential cardioprotective effects of cyclosporin in man. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  19. Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1

    PubMed Central

    Yang, Long; Xie, Peng; Wu, Jianjiang; Yu, Jin; Yu, Tian; Wang, Haiying; Wang, Jiang; Xia, Zhengyuan; Zheng, Hong

    2016-01-01

    Background: Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats. Methods: The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, postconditioning was performed using sevoflurane alone or in combination with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). The changes in hemodynamic parameters, HIF-1α protein expression levels, mitochondrial respiratory function and enzyme activity, mitochondrial reactive oxygen species (ROS) production rates, and mitochondrial ultrastructure were measured or observed. Results: Compared to the ischemia-reperfusion (I/R) group, HIF-1α expression in the SPostC group was significantly up-regulated. Additionally, cardiac function indicators, mitochondrial state 3 respiratory rate, respiratory control ratio (RCR), cytochrome C oxidase (CcO), NADH oxidase (NADHO), and succinate oxidase (SUCO) activities, mitochondrial ROS production rate, and mitochondrial ultrastructure were significantly better than those in the I/R group. However, these advantages were completely reversed by the HIF-1α specific inhibitor 2ME2 (P<0.05). Conclusion: The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1α expression. PMID:27830025

  20. Phellinus linteus Mycelium Alleviates Myocardial Ischemia-Reperfusion Injury through Autophagic Regulation.

    PubMed

    Su, Hsing-Hui; Chu, Ya-Chun; Liao, Jiuan-Miaw; Wang, Yi-Hsin; Jan, Ming-Shiou; Lin, Chia-Wei; Wu, Chiu-Yeh; Tseng, Chin-Yin; Yen, Jiin-Cherng; Huang, Shiang-Suo

    2017-01-01

    The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly increasing around the world and this disease is a major contributor to global morbidity and mortality. It is known that regulation of programmed cell death including apoptosis and autophagy reduces the impact of myocardial IR injury. In this study, the cardioprotective effects and underlying mechanisms of Phellinus linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal mushroom, were examined in rats subjected to myocardial IR injury. The left main coronary artery of rats was ligated for 1 h and reperfused for 3 h. The arrhythmia levels were monitored during the entire process and the infarct size was evaluated after myocardial IR injury. Furthermore, the expression levels of proteins in apoptotic and autophagic pathways were observed. Pretreatment with PL mycelium (PLM) significantly reduced ventricular arrhythmia and mortality due to myocardial IR injury. PLM also significantly decreased myocardial infarct size and plasma lactate dehydrogenase level after myocardial IR injury. Moreover, PLM administration resulted in decreased caspase 3 and caspase 9 activation and increased Bcl-2/Bax ratio. Phosphorylation level of AMPK was elevated while mTOR level was reduced. Becline-1 and p62 levels decreased. These findings suggest that PLM is effective in protecting the myocardium against IR injury. The mechanism involves mediation through suppressed pro-apoptotic signaling and regulation of autophagic signaling, including stimulation of AMPK-dependent pathway and inhibition of beclin-1-dependent pathway, resulting in enhancement of protective autophagy and inhibition of excessive autophagy.

  1. Phellinus linteus Mycelium Alleviates Myocardial Ischemia-Reperfusion Injury through Autophagic Regulation

    PubMed Central

    Su, Hsing-Hui; Chu, Ya-Chun; Liao, Jiuan-Miaw; Wang, Yi-Hsin; Jan, Ming-Shiou; Lin, Chia-Wei; Wu, Chiu-Yeh; Tseng, Chin-Yin; Yen, Jiin-Cherng; Huang, Shiang-Suo

    2017-01-01

    The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly increasing around the world and this disease is a major contributor to global morbidity and mortality. It is known that regulation of programmed cell death including apoptosis and autophagy reduces the impact of myocardial IR injury. In this study, the cardioprotective effects and underlying mechanisms of Phellinus linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal mushroom, were examined in rats subjected to myocardial IR injury. The left main coronary artery of rats was ligated for 1 h and reperfused for 3 h. The arrhythmia levels were monitored during the entire process and the infarct size was evaluated after myocardial IR injury. Furthermore, the expression levels of proteins in apoptotic and autophagic pathways were observed. Pretreatment with PL mycelium (PLM) significantly reduced ventricular arrhythmia and mortality due to myocardial IR injury. PLM also significantly decreased myocardial infarct size and plasma lactate dehydrogenase level after myocardial IR injury. Moreover, PLM administration resulted in decreased caspase 3 and caspase 9 activation and increased Bcl-2/Bax ratio. Phosphorylation level of AMPK was elevated while mTOR level was reduced. Becline-1 and p62 levels decreased. These findings suggest that PLM is effective in protecting the myocardium against IR injury. The mechanism involves mediation through suppressed pro-apoptotic signaling and regulation of autophagic signaling, including stimulation of AMPK-dependent pathway and inhibition of beclin-1-dependent pathway, resulting in enhancement of protective autophagy and inhibition of excessive autophagy. PMID:28420993

  2. Stromal cell derived factor-1 (SDF-1) targeting reperfusion reduces myocardial infarction in isolated rat hearts.

    PubMed

    Jang, Young-Ho; Kim, June-Hong; Ban, Changill; Ahn, Kyohan; Cheong, Jae-Hun; Kim, Hyung-Hoi; Kim, Jung-Soo; Park, Yong-Hyun; Kim, Jun; Chun, Kook-Jin; Lee, Gyeong-Ho; Kim, Miju; Kim, Cheolmin; Xu, Zhelong

    2012-10-01

    Recent studies have shown that stromal cell derived factor-1 (SDF-1), first known as a cytokine involved in recruiting stem cells into injured organs, confers myocardial protection in myocardial infarction, which is not dependent on stem cell recruitment but related with modulation of ischemia-reperfusion (I/R) injury. However, the effect of SDF has been studied only in a preischemic exposure model, which is not clinically relevant if SDF is to be used as a therapeutic agent. Our study was aimed at evaluating whether or not SDF-1 confers cardioprotection during the reperfusion period. Hearts from SD rats were isolated and perfused with the Langendorff system. Proximal left coronary artery ligation, reperfusion, and SDF perfusion in KH buffer was done according to study protocol. Area of necrosis (AN) relative to area at risk (AR) was the primary endpoint of the study. Significant reduction of AN/AR by SDF in an almost dose-dependent manner was noted during both the preischemic exposure and reperfusion periods. In particular, infusion of a high concentration of SDF (25 nM/L) resulted in a dramatic reduction of infarct size, which was greater than that achieved with ischemic pre- or postconditioning. SDF perfusion during reperfusion was associated with a similar significant reduction of infarct size as preischemic SDF exposure. Further studies are warranted to assess the potential of SDF as a therapeutic agent for reducing I/R injury in clinical practice.

  3. Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Herzog, Christine; Schmitz, Martina; Levkau, Bodo; Herrgott, Ilka; Mersmann, Jan; Larmann, Jan; Johanning, Kai; Winterhalter, Michael; Chun, Jerold; Müller, Frank Ulrich; Echtermeyer, Frank; Hildebrand, Reinhard; Theilmeier, Gregor

    2010-01-01

    HDL, through sphingosine-1-phosphate (S1P), exerts direct cardioprotective effects on ischemic myocardium. It remains unclear whether other HDL-associated sphingophospholipids have similar effects. We therefore examined if HDL-associated sphingosylphosphorylcholine (SPC) reduces infarct size in a mouse model of transient myocardial ischemia/reperfusion. Intravenously administered SPC dose-dependently reduced infarct size after 30 minutes of myocardial ischemia and 24 hours reperfusion compared to controls. Infarct size was also reduced by postischemic, therapeutical administration of SPC. Immunohistochemistry revealed reduced polymorphonuclear neutrophil recruitment to the infarcted area after SPC treatment, and apoptosis was attenuated as measured by TUNEL. In vitro, SPC inhibited leukocyte adhesion to TNFα-activated endothelial cells and protected rat neonatal cardiomyocytes from apoptosis. S1P3 was identified as the lysophospholipid receptor mediating the cardioprotection by SPC, since its effect was completely absent in S1P3-deficient mice. We conclude that HDL-associated SPC directly protects against myocardial reperfusion injury in vivo via the S1P3 receptor. PMID:21274265

  4. Blockage of transient receptor potential vanilloid 4 alleviates myocardial ischemia/reperfusion injury in mice

    PubMed Central

    Dong, Qian; Li, Jing; Wu, Qiong-feng; Zhao, Ning; Qian, Cheng; Ding, Dan; Wang, Bin-bin; Chen, Lei; Guo, Ke-Fang; Fu, Dehao; Han, Bing; Liao, Yu-Hua; Du, Yi-Mei

    2017-01-01

    Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 can alleviate myocardial I/R injury in mice. TRPV4 expression began to increase at 1 h, reached statistically at 4 h, and peaked at 24–72 h. Treatment with the selective TRPV4 antagonist HC-067047 or TRPV4 knockout markedly ameliorated myocardial I/R injury as demonstrated by reduced infarct size, decreased troponin T levels and improved cardiac function at 24 h after reperfusion. Importantly, the therapeutic window for HC-067047 lasts for at least 12 h following reperfusion. Furthermore, treatment with HC-067047 reduced apoptosis, as evidenced by the decrease in TUNEL-positive myocytes, Bax/Bcl-2 ratio, and caspase-3 activation. Meanwhile, treatment with HC-067047 attenuated the decrease in the activation of reperfusion injury salvage kinase (RISK) pathway (phosphorylation of Akt, ERK1/2, and GSK-3β), while the activation of survival activating factor enhancement (SAFE) pathway (phosphorylation of STAT3) remained unchanged. In addition, the anti-apoptotic effects of HC-067047 were abolished by the RISK pathway inhibitors. We conclude that blockade of TRPV4 reduces apoptosis via the activation of RISK pathway, and therefore might be a promising strategy to prevent myocardial I/R injury. PMID:28205608

  5. Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion.

    PubMed

    Okere, Isidore C; McElfresh, Tracy A; Brunengraber, Daniel Z; Martini, Wenjun; Sterk, Joseph P; Huang, Hazel; Chandler, Margaret P; Brunengraber, Henri; Stanley, William C

    2006-01-01

    In the normal heart, there is loss of citric acid cycle (CAC) intermediates that is matched by the entry of intermediates from outside the cycle, a process termed anaplerosis. Previous in vitro studies suggest that supplementation with anaplerotic substrates improves cardiac function during myocardial ischemia and/or reperfusion. The present investigation assessed whether treatment with the anaplerotic medium-chain fatty acid heptanoate improves contractile function during ischemia and reperfusion. The left anterior descending coronary artery of anesthetized pigs was subjected to 60 min of 60% flow reduction and 30 min of reperfusion. Three treatment groups were studied: saline control, heptanoate (0.4 mM), or hexanoate as a negative control (0.4 mM). Treatment was initiated after 30 min of ischemia and continued through reperfusion. Myocardial CAC intermediate content was not affected by ischemia-reperfusion; however, treatment with heptanoate resulted in a more than twofold increase in fumarate and malate, with no change in citrate and succinate, while treatment with hexanoate did not increase fumarate or malate but increased succinate by 1.8-fold. There were no differences among groups in lactate exchange, glucose oxidation, oxygen consumption, and contractile power. In conclusion, despite a significant increase in the content of carbon-4 CAC intermediates, treatment with heptanoate did not result in improved mechanical function of the heart in this model of reversible ischemia-reperfusion. This suggests that reduced anaplerosis and CAC dysfunction do not play a major role in contractile and metabolic derangements observed with a 60% decrease in coronary flow followed by reperfusion.

  6. Short-term fasting reduces the extent of myocardial infarction and incidence of reperfusion arrhythmias in rats.

    PubMed

    Snorek, M; Hodyc, D; Sedivý, V; Durišová, J; Skoumalová, A; Wilhelm, J; Neckář, J; Kolář, F; Herget, J

    2012-01-01

    The effect of three-day fasting on cardiac ischemic tolerance was investigated in adult male Wistar rats. Anesthetized open-chest animals (pentobarbitone 60 mg/kg, i.p.) were subjected to 20-min left anterior descending coronary artery occlusion and 3-h reperfusion for infarct size determination. Ventricular arrhythmias were monitored during ischemia and at the beginning (3 min) of reperfusion. Myocardial concentrations of beta-hydroxybutyrate and acetoacetate were measured to assess mitochondrial redox state. Short-term fasting limited the infarct size (48.5+/-3.3 % of the area at risk) compared to controls (74.3+/-2.2 %) and reduced the total number of premature ventricular complexes (12.5+/-5.8) compared to controls (194.9+/-21.9) as well as the duration of ventricular tachycardia (0.6+/-0.4 s vs. 18.8+/-2.5 s) occurring at early reperfusion. Additionally, fasting increased the concentration of beta-hydroxybutyrate and beta-hydroxybutyrate/acetoacetate ratio (87.8+/-27.0) compared to controls (7.9+/-1.7), reflecting altered mitochondrial redox state. It is concluded that three-day fasting effectively protected rat hearts against major endpoints of acute I/R injury. Further studies are needed to find out whether these beneficial effects can be linked to altered mitochondrial redox state resulting from increased ketogenesis.

  7. Real time measurement of myocardial oxygen dynamics during cardiac ischemia-reperfusion of rats.

    PubMed

    Lee, Gi-Ja; Kim, Seung Ki; Kang, Sung Wook; Kim, Ok-Kyun; Chae, Su-Jin; Choi, Samjin; Shin, Jae Ho; Park, Hun-Kuk; Chung, Joo-Ho

    2012-11-21

    Because oxygen plays a critical role in the pathophysiology of myocardial injury during subsequent reperfusion, as well as ischemia, the accurate measurement of myocardial oxygen tension is crucial for the assessment of myocardial viability by ischemia-reperfusion (IR) injury. Therefore, we utilized a sol-gel derived electrochemical oxygen microsensor to monitor changes in oxygen tension during myocardial ischemia-reperfusion. We also analyzed differences in oxygen tension recovery in post-ischemic myocardium depending on ischemic time to investigate the correlation between recovery parameters for oxygen tension and the severity of IR injury. An oxygen sensor was built using a xerogel-modified platinum microsensor and a coiled Ag/AgCl reference electrode. Rat hearts were randomly divided into 5 groups: control (0 min ischemia), I-10 (10 min ischemia), I-20 (20 min ischemia), I-30 (30 min ischemia), and I-40 (40 min ischemia) groups (n = 3 per group, respectively). After the induction of ischemia, reperfusion was performed for 60 min. As soon as the ischemia was initiated, oxygen tension rapidly declined to near zero levels. When reperfusion was initiated, the changes in oxygen tension depended on ischemic time. The normalized peak level of oxygen tension during the reperfusion episode was 188 ± 27 in group I-10, 120 ± 24 in group I-20, 12.5 ± 10.6 in group I-30, and 1.24 ± 1.09 in group I-40 (p < 0.001, n = 3, respectively). After 60 min of reperfusion, the normalized restoration level was 129 ± 30 in group I-10, 88 ± 4 in group I-20, 3.40 ± 4.82 in group I-30, and 0.99 ± 0.94 in group I-40 (p < 0.001, n = 3, respectively). The maximum and restoration values of oxygen tension in groups I-30 and I-40 after reperfusion were lower than pre-ischemic values. In particular, oxygen tension in the I-40 group was not recovered at all. These results were also demonstrated by TTC staining. We suggest that these recovery parameters could be utilized as an index of

  8. Selective Localization of a Novel Dendrimer Nanoparticle in Myocardial Ischemia-Reperfusion Injury.

    PubMed

    Magruder, J Trent; Crawford, Todd C; Lin, Yi-An; Zhang, Fan; Grimm, Joshua C; Kannan, Rangaramanujam M; Kannan, Sujatha; Sciortino, Christopher M

    2017-09-01

    Dendrimer nanoparticle therapies represent promising new approaches to drug delivery, particularly in diseases associated with inflammatory injury. However, their application has not been fully explored in models of acute myocardial ischemia (MI) and reperfusion injury. White male New Zealand rabbits underwent left thoracotomy with 30-minute temporary left anterior descending artery occlusion and MI confirmed by electrocardiography and histology (MI rabbits, n = 9), or left thoracotomy and pericardial opening for 30 minutes but no left anterior descending artery occlusion (control [C] rabbits, n = 9) rabbits. Following the 30-minute period, a dendrimer (generation 6 dendrimer conjugated to cyanine-5 fluorescent dye [G6-Cy5], 6.7 nm diameter) was administered intravenously and the chest closed in layers. Animals were sacrificed at 3 hours (3 MI, 3 C), 24 hours (3 MI, 3 C), or 48 hours (3 MI, 3 C) postsurgery. As compared to controls, MI rabbits had twofold G6-Cy5 uptake in the myocardial anterior wall as compared to the same region in nonischemic control rabbits at 24 hours postsurgery (6.01 ± 0.57 μg/g versus 2.85 ± 0.85 μg/g; p = 0.04). This trend was also present at 48 hours (6.38 ± 1.53 μg/g versus 3.95 ± 0.60 μg/g, p = 0.21) and was qualitatively evident on confocal microscopy. G6-Cy5 half-life in serum was approximately 12 hours, with 22% of the injected G6-Cy5 dose remaining at 48 hours. This study demonstrates for the first time that dendrimer nanodevices selectively localize in ischemic as compared to healthy myocardium. This indicates that dendrimer nanodevices are promising agents to deliver drugs specifically to the ischemic myocardium to attenuate the injury. Subsequent studies will assess the efficacy of a dendrimer-drug conjugate in ameliorating reperfusion injury following MI. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Cardioprotective activity of chalcones in ischemia/reperfusion-induced myocardial infarction in albino rats

    PubMed Central

    Annapurna, Akula; Mudagal, Manjunatha P; Ansari, Asif; Rao A, Srinivasa

    2012-01-01

    BACKGROUND: There is a comprehensive body of experimental and clinical evidence suggesting that exogenous supplementation of natural antioxidants or augmentation of endogenous antioxidants attenuates the damage caused by myocardial infarction. OBJECTIVE: To evaluate the cardioprotective effects of Cl-chalcone and F-chalcone against ischemia/reperfusion (I/R)-induced myocardial infarction in rats. METHODS: Myocardial infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. Malondialdehyde was measured in serum and heart tissue, and superoxide dismutase and catalase in heart tissue were measured spectrophotometrically. RESULTS: I/R resulted in significant cardiac necrosis, indicated by a rise in the end products of myocardial lipid peroxidation (malondialdehydes). A loss of antioxidative enzymes (superoxide dismutase and catalase) in heart tissue was also observed in animals subjected to in vivo myocardial I/R injury. DISCUSSION: The present study demonstrated that treatment with Cl-chalcone and F-chalcone significantly limited infarct size, partially but significantly attenuated the level of lipid peroxidation and moderated the loss of antioxidant reserves in rats subjected to 30 min coronary artery occlusion followed by a 4 h reperfusion in comparison with I/R groups. CONCLUSIONS: The results of the present study suggest that chalcones have cardioprotective activity against I/R-induced myocardial infarction in rats. PMID:23620697

  10. Cardioprotective activity of chalcones in ischemia/reperfusion-induced myocardial infarction in albino rats.

    PubMed

    Annapurna, Akula; Mudagal, Manjunatha P; Ansari, Asif; Rao A, Srinivasa

    2012-09-01

    There is a comprehensive body of experimental and clinical evidence suggesting that exogenous supplementation of natural antioxidants or augmentation of endogenous antioxidants attenuates the damage caused by myocardial infarction. To evaluate the cardioprotective effects of Cl-chalcone and F-chalcone against ischemia/reperfusion (I/R)-induced myocardial infarction in rats. Myocardial infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. Malondialdehyde was measured in serum and heart tissue, and superoxide dismutase and catalase in heart tissue were measured spectrophotometrically. I/R resulted in significant cardiac necrosis, indicated by a rise in the end products of myocardial lipid peroxidation (malondialdehydes). A loss of antioxidative enzymes (superoxide dismutase and catalase) in heart tissue was also observed in animals subjected to in vivo myocardial I/R injury. The present study demonstrated that treatment with Cl-chalcone and F-chalcone significantly limited infarct size, partially but significantly attenuated the level of lipid peroxidation and moderated the loss of antioxidant reserves in rats subjected to 30 min coronary artery occlusion followed by a 4 h reperfusion in comparison with I/R groups. The results of the present study suggest that chalcones have cardioprotective activity against I/R-induced myocardial infarction in rats.

  11. Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury.

    PubMed

    Chen, Gangbin; Yang, Li; Zhong, Lintao; Kutty, Shelby; Wang, Yuegang; Cui, Kai; Xiu, Jiancheng; Cao, Shiping; Huang, Qiaobing; Liao, Wangjun; Liao, Yulin; Wu, Juefei; Zhang, Wenzhu; Bin, Jianping

    2016-07-29

    Hydrogen sulfide (H2S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H2S may cause unwanted side effects. Ultrasound targeted microbubble destruction has become a promising tool for organ specific delivery of bioactive substance. We hypothesized that delivery of H2S by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury and could avoid unwanted side effects. We prepared microbubbles carrying hydrogen sulfide (hs-MB) with different H2S/C3F8 ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H2S triggered by ultrasound was investigated. The cardioprotective effect of ultrasound targeted hs-MB destruction was investigated in a rodent model of myocardial ischemia-reperfusion injury. The H2S/C3F8 ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H2S loading capability. Ultrasound targeted hs-MB destruction triggered H2S release and increased the concentration of H2S in the myocardium and lung. Ultrasound targeted hs-MB destruction limited myocardial infarct size, preserved left ventricular function and had no influence on haemodynamics and respiratory. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. Delivery of H2S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects.

  12. Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury

    PubMed Central

    Chen, Gangbin; Yang, Li; Zhong, Lintao; Kutty, Shelby; Wang, Yuegang; Cui, Kai; Xiu, Jiancheng; Cao, Shiping; Huang, Qiaobing; Liao, Wangjun; Liao, Yulin; Wu, Juefei; Zhang, Wenzhu; Bin, Jianping

    2016-01-01

    Hydrogen sulfide (H2S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H2S may cause unwanted side effects. Ultrasound targeted microbubble destruction has become a promising tool for organ specific delivery of bioactive substance. We hypothesized that delivery of H2S by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury and could avoid unwanted side effects. We prepared microbubbles carrying hydrogen sulfide (hs-MB) with different H2S/C3F8 ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H2S triggered by ultrasound was investigated. The cardioprotective effect of ultrasound targeted hs-MB destruction was investigated in a rodent model of myocardial ischemia-reperfusion injury. The H2S/C3F8 ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H2S loading capability. Ultrasound targeted hs-MB destruction triggered H2S release and increased the concentration of H2S in the myocardium and lung. Ultrasound targeted hs-MB destruction limited myocardial infarct size, preserved left ventricular function and had no influence on haemodynamics and respiratory. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. Delivery of H2S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects. PMID:27469291

  13. Impact of active smoking on myocardial infarction severity in reperfused ST-segment elevation myocardial infarction patients: the smoker's paradox revisited.

    PubMed

    Symons, Rolf; Masci, Pier Giorgio; Francone, Marco; Claus, Piet; Barison, Andrea; Carbone, Iacopo; Agati, Luciano; Galea, Nicola; Janssens, Stefan; Bogaert, Jan

    2016-09-21

    To investigate the influence of cardiovascular risk factors (CV-RFs) on infarct severity and post-infarction left ventricular (LV) remodelling in acutely reperfused ST-segment elevation myocardial infarction (STEMI) patients studied with cardiovascular magnetic resonance (CMR). Four-hundred seventy-one patients were included in the study. Baseline CMR was performed at 4 ± 1 days after STEMI to assess area-at-risk, infarct size (IS), myocardial salvage index (MSI), microvascular obstruction (MVO), intramyocardial haemorrhage (IMH), LV volumes, and function. Cardiovascular magnetic resonance was repeated 4 months after STEMI (n = 383) to assess adverse LV remodelling (increase of LV end-diastolic volume >20% between baseline and follow-up). Smoking was associated with IMH at baseline even after correction for other factors associated with ischaemia-reperfusion injury including MVO, IS, and MSI (OR: 2.17, 95% CI: 1.17-4.00, P = 0.01). Unexpectedly, smoking was an independent protective predictor against adverse LV remodelling (OR: 0.43, 95% CI: 0.24-0.77, P = 0.005), consistent with the 'smoker's paradox'. However, the presence of IMH at baseline abolished the paradoxical, beneficial effects of smoking with respect to IS, baseline LV function, and post-infarction LV remodelling. No association between other CV-RFs, infarct severity, or post-infarction LV remodelling was observed. In patients with reperfused STEMI, smoking is strongly and independently associated with IMH at baseline. Nonetheless, consistent with the 'smoker's paradox', smoking was an independent predictor of more favourable post-infarction LV remodelling. However, the paradoxical beneficial effects of smoking were lost in patients with IMH. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  14. Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the erythropoietin in myocardial infarction trial.

    PubMed

    Prunier, Fabrice; Bière, Loïc; Gilard, Martine; Boschat, Jacques; Mouquet, Frédéric; Bauchart, Jean-Jacques; Charbonnier, Bernard; Genée, Olivier; Guérin, Patrice; Warin-Fresse, Karine; Durand, Eric; Lafont, Antoine; Christiaens, Luc; Abi-Khalil, Wissam; Delépine, Stéphane; Benard, Thomas; Furber, Alain

    2012-02-01

    Preclinical studies and pilot clinical trials have shown that high-dose erythropoietin (EPO) reduces infarct size in acute myocardial infarction. We investigated whether a single high-dose of EPO administered immediately after reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) would limit infarct size. A total of 110 patients undergoing successful primary coronary intervention for a first STEMI was randomized to receive standard care either alone (n = 57) or combined with intravenous administration of 1,000 U/kg of epoetin β immediately after reperfusion (n = 53). The primary end point was infarct size assessed by gadolinium-enhanced cardiac magnetic resonance after 3 months. Secondary end points included left ventricular (LV) volume and function at 5-day and 3-month follow-up, incidence of microvascular obstruction (MVO), and safety. Erythropoietin significantly decreased the incidence of MVO (43.4% vs 65.3% in the control group, P = .03) and reduced LV volume, mass, and function impairment at 5-day follow-up (all P < .05). After 3 months, median infarct size (interquartile range) was 17.5 g (7.6-26.1 g) in the EPO group and 16.0 g (9.4-28.2 g) in the control group (P = .64); LV mass, volume, and function were not significantly different between the 2 groups. The same number of major adverse cardiac events occurred in both groups. Single high-dose EPO administered immediately after successful reperfusion in patients with STEMI did not reduce infarct size at 3-month follow-up. However, this regimen decreased the incidence of MVO and was associated with transient favorable effects on LV volume and function. Copyright © 2012 Mosby, Inc. All rights reserved.

  15. Thallium-201 myocardial scintigraphy in acute myocardial infarction and ischemia

    SciTech Connect

    Wackers, F.J.

    1982-04-01

    Thallium-201 scintigraphy provides a sensitive and reliable method of detecting acute myocardial infarction and ischemia when imaging is performed with understanding of the temporal characteristics and accuracy of the technique. The results of scintigraphy are related to the time interval between onset of symptoms and time of imaging. During the first 6 hr after chest pain almost all patients with acute myocardial infarction and approximately 50% of the patients with unstable angina will demonstrate /sup 201/TI pefusion defects. Delayed imaging at 2-4 hr will permit distinction between ischemia and infarction. In patients with acute myocardial infarction, the size of the perfusion defect accurately reflects the extent of the infarcted and/or jeopardized myocardium, which may be used for prognostic stratification. In view of the characteristics of /sup 201/TI scintigraphy, the most practical application of this technique is in patients in whom myocardial infarction has to be ruled out, and for early recognition of patients at high risk for complications.

  16. [Impact of comorbidities on in-hospital mortality from acute myocardial infarction, 2003-2009].

    PubMed

    Gili, Miguel; Sala, José; López, Julio; Carrión, Ana; Béjar, Luís; Moreno, Julio; Rosales, Angela; Sánchez, Gabriel

    2011-12-01

    Treatment of acute myocardial infarction has changed notably in recent years. The objective of this study was to analyze trends in in-hospital mortality during the period 2003-2009 and to examine how changes in comorbidity indices affected mortality prediction models for acute myocardial infarction using the minimum basic data set. During the study period, 5275 cases of acute myocardial infarction were admitted. Mortality rates were calculated by age and sex and Charlson and Elixhauser comorbidity index scores were obtained on admission for every patient. Trends were analyzed and their validity studied. Multivariate models predictive of mortality were derived and compared. Mean age and comorbidities increased in all patients over the period 2003-2009. In spite of these trends, acute myocardial infarction mortality decreased. Comorbidity indices remained valid when the criterion "present on admission" was applied. Multivariate predictive models included age, sex, medical treatment, coronary revascularization and a comorbidity index or specific comorbidities. The model with specific comorbidities showed the best predictive ability. All models found that age and comorbidities increased the risk of death, and that coronary revascularization and treatment with anticoagulants, fibrinolytics, and platelet antiaggregants were protective factors. Despite the fact that the mean age and number of comorbidities in acute myocardial infarction patients has increased year over year, acute myocardial infarction mortality has decreased, probably because of more frequent reperfusion and revascularization therapy and better medical treatment. Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  17. Detecting Acute Myocardial Infarction by Diffusion-Weighted versus T2-Weighted Imaging and Myocardial Necrosis Markers

    PubMed Central

    Chen, Min; Li, Yongjun; Wang, YaLing; Zhang, Shijun; Wang, Zhen; Wang, Lin; Ju, Shenghong

    2016-01-01

    We used a porcine model of acute myocardial infarction to study the signal evolution of ischemic myocardium on diffusion-weighted magnetic resonance images (DWI). Eight Chinese miniature pigs underwent percutaneous left anterior descending or left circumflex coronary artery occlusion for 90 minutes followed by reperfusion, which induced acute myocardial infarction. We used DWI preprocedurally and hourly for 4 hours postprocedurally. We acquired turbo inversion recovery magnitude T2-weighted images (TIRM T2WI) and late gadolinium enhancement images from the DWI slices. We measured the serum myocardial necrosis markers myoglobin, creatine kinase-MB isoenzyme, and cardiac troponin I at the same time points as the magnetic resonance scanning. We used histochemical staining to confirm injury. All images were analyzed qualitatively. Contrast-to-noise ratio (the contrast between infarcted and healthy myocardium) and relative signal index were used in quantitative image analysis. We found that DWI identified myocardial signal abnormity early (<4 hr) after acute myocardial infarction and identified the infarct-related high signal more often than did TIRM T2WI: 7 of 8 pigs (87.5%) versus 3 of 8 (37.5%) (P=0.046). Quantitative image analysis yielded a significant difference in contrast-to-noise ratio and relative signal index between infarcted and normal myocardium on DWI. However, within 4 hours after infarction, the serologic myocardial injury markers were not significantly positive. We conclude that DWI can be used to detect myocardial signal abnormalities early after acute myocardial infarction—identifying the infarction earlier than TIRM T2WI and widely used clinical serologic biomarkers. PMID:27777517

  18. Detecting Acute Myocardial Infarction by Diffusion-Weighted versus T2-Weighted Imaging and Myocardial Necrosis Markers.

    PubMed

    Jin, Jiyang; Chen, Min; Li, Yongjun; Wang, YaLing; Zhang, Shijun; Wang, Zhen; Wang, Lin; Ju, Shenghong

    2016-10-01

    We used a porcine model of acute myocardial infarction to study the signal evolution of ischemic myocardium on diffusion-weighted magnetic resonance images (DWI). Eight Chinese miniature pigs underwent percutaneous left anterior descending or left circumflex coronary artery occlusion for 90 minutes followed by reperfusion, which induced acute myocardial infarction. We used DWI preprocedurally and hourly for 4 hours postprocedurally. We acquired turbo inversion recovery magnitude T2-weighted images (TIRM T2WI) and late gadolinium enhancement images from the DWI slices. We measured the serum myocardial necrosis markers myoglobin, creatine kinase-MB isoenzyme, and cardiac troponin I at the same time points as the magnetic resonance scanning. We used histochemical staining to confirm injury. All images were analyzed qualitatively. Contrast-to-noise ratio (the contrast between infarcted and healthy myocardium) and relative signal index were used in quantitative image analysis. We found that DWI identified myocardial signal abnormity early (<4 hr) after acute myocardial infarction and identified the infarct-related high signal more often than did TIRM T2WI: 7 of 8 pigs (87.5%) versus 3 of 8 (37.5%) (P=0.046). Quantitative image analysis yielded a significant difference in contrast-to-noise ratio and relative signal index between infarcted and normal myocardium on DWI. However, within 4 hours after infarction, the serologic myocardial injury markers were not significantly positive. We conclude that DWI can be used to detect myocardial signal abnormalities early after acute myocardial infarction-identifying the infarction earlier than TIRM T2WI and widely used clinical serologic biomarkers.

  19. [ln-hospital mortality after ST-segment elevation myocardial infarction according to reperfusion therapy].

    PubMed

    Prieto, Juan Carlos; Sanhueza, Consuelo; Martínez, Nicolás; Nazzal, Carolina; Corbalán, Ramón; Cavada, Gabriel; Lanas, Fernando; Bartolucci, Jorge; Campos, Pabla

    2008-02-01

    Primary angioplasty is considered the best reperfusion therapy in the treatment of ST-segment elevation myocardial infarction (STEMI). However, thrombolysis is the reperfusion method most commonly used, due to its wide availability, reduced costs and ease of administration. To compare in-hospital mortality in STEMI patients according to reperfusion therapy. Patients admitted to Chilean hospitals participating in the GEMI network, from 2001 to 2005, with STEMI were included. They were divided in three groups: a) treated with thrombolytics, b) treated with primary angioplasty, c) without reperfusion procedure. In-hospital mortality according to gender, was analyzed in each group, using a logistic regression method, to assess risk factors associated with mortality. We included 3,255 patients. Global mortality was 9.9% (7.5% in men and 16.7% in women, p<0.001). Mortality in patients treated with thrombolytics, was 10.2% (7.6% in men and 18.7% in women, p<0.01). The figure for patients treated with primary angioplasty, was 4.7% (2.5% in men and 13% in women, p<0.01), and in patients without reperfusion, was 11.6% (9.8% in men and in 15.4% women, p<0.01). In each group women were older, had a higher prevalence of hypertension and a higher percentage of Killip 3-4 infarctions. Logistic regression showed that angioplasty, compared with no reperfusion, was associated with a reduced mortality only in men. The use of thrombolytics in women was associated with a higher mortality. Primary angioplasty was the reperfusion therapy associated to the lower mortality in STEMI. Use of thrombolytics in women was associated with a higher mortality rate than in non reperfused women.

  20. Amifostine Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Apoptosis and Oxidative Stress

    PubMed Central

    Wu, Shao-ze; Tao, Lu-yuan; Wang, Jiao-ni; Xu, Zhi-qiang; Wang, Jie; Xue, Yang-jing; Huang, Kai-yu; Lin, Jia-feng; Li, Lei

    2017-01-01

    The present study was aimed at investigating the effect of amifostine on myocardial ischemia/reperfusion (I/R) injury of mice and H9c2 cells cultured with TBHP (tert-butyl hydroperoxide). The results showed that pretreatment with amifostine significantly attenuated cell apoptosis and death, accompanied by decreased reactive oxygen species (ROS) production and lower mitochondrial potential (ΔΨm). In vivo, amifostine pretreatment alleviated I/R injury and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase (SOD) and reduced malondialdehyde (MDA) in myocardial tissues, increased Bcl2 expression, decreased Bax expression, lower cleaved caspase-3 level, fewer TUNEL positive cells, and fewer DHE-positive cells in heart. Our results indicate that amifostine pretreatment has a protective effect against myocardial I/R injury via scavenging ROS. PMID:28392886

  1. Balance of nitric oxide and reactive oxygen species in myocardial reperfusion injury and protection.

    PubMed

    Folino, Anna; Losano, Gianni; Rastaldo, Raffaella

    2013-12-01

    Depending on their concentrations, both nitric oxide (NO) and reactive oxygen species (ROS) take part either in myocardial ischemia reperfusion injury or in protection by ischemic and pharmacological preconditioning (Ipre) and postconditioning (Ipost). At the beginning of reperfusion, a transient release of NO is promptly scavenged by ROS to form the highly toxic peroxynitrite, which is responsible for a further increase of ROS through endothelial nitric oxide synthase uncoupling. The protective role of NO has suggested the use of NO donors to mimic Ipre and Ipost. However, NO donors have not always given the expected protection, possibly because they are responsible for the production of different amounts of ROS that depend on the amount of released NO. This review is focused on the role of the balance of NO and ROS in myocardial injury and its prevention by Ipre and Ipost and after the use of NO donors given with or without antioxidant compounds to mimic Ipre and Ipost.

  2. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

    PubMed Central

    Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

    2016-01-01

    Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

  3. Molecular Characterization of Reactive Oxygen Species in Myocardial Ischemia-Reperfusion Injury.

    PubMed

    Zhou, Tingyang; Chuang, Chia-Chen; Zuo, Li

    2015-01-01

    Myocardial ischemia-reperfusion (I/R) injury is experienced by individuals suffering from cardiovascular diseases such as coronary heart diseases and subsequently undergoing reperfusion treatments in order to manage the conditions. The occlusion of blood flow to the tissue, termed ischemia, can be especially detrimental to the heart due to its high energy demand. Several cellular alterations have been observed upon the onset of ischemia. The danger created by cardiac ischemia is somewhat paradoxical in that a return of blood to the tissue can result in further damage. Reactive oxygen species (ROS) have been studied intensively to reveal their role in myocardial I/R injury. Under normal conditions, ROS function as a mediator in many cell signaling pathways. However, stressful environments significantly induce the generation of ROS which causes the level to exceed body's antioxidant defense system. Such altered redox homeostasis is implicated in myocardial I/R injury. Despite the detrimental effects from ROS, low levels of ROS have been shown to exert a protective effect in the ischemic preconditioning. In this review, we will summarize the detrimental role of ROS in myocardial I/R injury, the protective mechanism induced by ROS, and potential treatments for ROS-related myocardial injury.

  4. Antioxidants decrease reperfusion induced arrhythmias in myocardial infarction with ST-elevation.

    PubMed

    Hicks, Juan J; Montes-Cortes, Daniel H; Cruz-Dominguez, Maria P; Medina-Santillan, Roberto; Olivares-Corichi, Ivonne M

    2007-01-01

    In myocardial infarctions with ST-segment elevation, ischemia followed by reperfusion (IR) leads to arrhythmia, myocardial stunning and endothelial dysfunction injury by reactive oxygen species (ROS). To determine the impact of ROS, we examined the effect of antioxidant vitamins on biochemical changes and arrhythmias induced by reperfusion before and after therapeutic thrombolysis (Actilyse). As compared with those receiving placebo, in individuals who received antioxidants, there was a significant decrease in premature ventricular beats (100% vs 38%), atrial fibrillation (44% vs 6%), ventricular tachycardia (31% vs 0%), first-degree atrial-ventricular block (44% vs 6%), plasma malondialdehyde at the first hour after initiation of thrombolysis (1.07 +/- 0.10 vs 0.53 +/- 0.10 nmols plasma malondialdehyde/mg protein) and circulating neutrophils after 24 hr after reperfusion. The antioxidant capacity of plasma was increased from 1.89 +/- 0.15 to 3.00 +/- 0.31 units/mg protein and paraoxonase-1 rose from 0.77 +/- 0.08 to 1.27 +/- 0.11 nmol/min/mg protein. These findings suggest that antioxidants might be useful as adjuvants in controlling reperfusion induced arrhythmias following therapeutic alteplase thrombolysis.

  5. Effect of pre- and posttreatment of losartan in feline model of myocardial ischemic-reperfusion injury.

    PubMed

    Kumari, R; Manchanda, S C; Maulik, S K

    2004-01-01

    This study investigated the differential effect of losartan, an AT1 receptor blocker, when administered in pre- and postischemic phases, on the biochemical, hemodynamic and oxidative stress associated with regional ischemic-reperfusion injury in cat. Losartan (5 microg/kg/min) or normal saline was administered intravenously in open chest barbiturate anesthetized cats, 15 min before and 10 min after the occlusion of the left anterior descending (LAD) coronary artery. The LAD was occluded for 15 min followed by 60 min reperfusion. In the saline treated group, there was significant depression of hemodynamic functions, i.e., mean arterial pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP) and left ventricular (LV) peak (+/-) dP/dt, along with depletion of adenosine triphosphate (ATP) of the affected myocardium. Oxidative stress during reperfusion injury was evidenced by significant increase in plasma thiobarbituric acid reactive substances (TBARS) accompanied by significant reduction in myocardial superoxide dismutase (SOD) activities. In both treatment groups, losartan caused recovery of all the hemodynamic parameters and repletion of ATP along with no significant change in plasma TBARS and myocardial SOD activity. There was no effect on catalase activity. Results from the study suggest that the effects of pre- and posttreatment of losartan are comparable in functional recovery of the heart from ischemic-reperfusion injury. (c) 2004 Prous Science. All rights reserved.

  6. [Protective effect of total glycosides of Ranunculus japonicus on myocardial ischemic-reperfusion injury in isolated rat hearts].

    PubMed

    Gao, Xiao-Wei; Liu, Yuan; Yang, Zhi-Cheng; Tan, Yu-Zhi

    2014-08-01

    To study the protective effect of total glycosides of Ranunculus japonicus (TGRJ) on myocardial ischemic-reperfusion injury in isolated rat hearts. The SD rats were randomly divided into normal control group, ischemia-reperfusion group, and TGRJ in 0.05, 0.10 and 0.20 mg/mL groups. The ischemia-reperfusion injury model was built using Langendroff isolated rats hearts perfusion system. The indexes of heart function such as heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular systolic pressure maximum rate of rise (+ dp/dt(max)), left ventricular diastolic pressure maximum rate of descent (-dp/dt(max)) and coronary flow (CF) before ischemia and later at 1, 5, 10, 20, 30 and 40 min after reperfusion were recorded. The activity of Lactate dehydrogenase (LDH) and creatine kinase (CK) at 20 and 40 min after reperfusion were determined. The myocardial tissues were stained with Triphenyltetrazolium chloride (TTC) and the percentage of myocardial infarction area was calculated. HR, LVDP, +dp/dt(max) and CF of the I/R group were significantly decreased after reperfusion, LDH and CK levels were increased and the area of myocardial infraction was 58.78%. TGRJ had improving effect on all above indexes. TGRJ has protective effet on the myo- cardial ischemic-reperfusion injury.

  7. Influence of acute glycaemic level on measures of myocardial infarction in non-diabetic pigs.

    PubMed

    Diemar, Sarah S; Sejling, Anne-Sophie; Iversen, Kasper K; Engstrøm, Thomas; Honge, Jesper L; Tønder, Niels; Vejlstrup, Niels; Idorn, Manja; Ekström, Kathrine; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger; Dalsgaard, Morten

    2015-01-01

    Patients with diabetes are at increased risk of experiencing myocardial infarction. The influence of the prevailing plasma glucose level on infarction and mortality after acute ischaemia is however unknown. The aim was to study the effect of the acute plasma glucose level on the myocardial infarction size in a closed-chest pig model. 38 non-diabetic pigs were randomised to hypoglycaemic (1.8-2.2 mmol/l; n = 15), normoglycaemic (5-7 mmol/l; n = 12) or hyperglycaemic glucose clamping (22-23 mmol/l; n = 11). After 30 min within glucose target myocardial infarction was induced for 30 min followed by reperfusion for 120 min. Hereafter the heart was double-stained to delineate infarction from viable tissue within the area at risk. Mean infarction size was 201 ± 35 mm(2) (mean ± SEM) in the hypoglycaemic group, 154 ± 40 mm(2) in the normoglycaemic group and 134 ± 40 mm(2) in the hyperglycaemic group, with no differences in infarction size, infarct/area at risk ratio or troponin T levels between the groups. There was no difference in incidence of ventricular fibrillation or mortality between the groups. No statistically significant associations were observed between the acute glycaemic level and measures of myocardial infarction, rates of ventricular fibrillation and subsequent premature death in the setting of acute ischaemia and reperfusion.

  8. Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction

    PubMed Central

    de Couto, Geoffrey; Liu, Weixin; Tseliou, Eleni; Sun, Baiming; Makkar, Nupur; Kanazawa, Hideaki; Arditi, Moshe; Marbán, Eduardo

    2015-01-01

    Ischemic injury in the heart induces an inflammatory cascade that both repairs damage and exacerbates scar tissue formation. Cardiosphere-derived cells (CDCs) are a stem-like population that is derived ex vivo from cardiac biopsies; they confer both cardioprotection and regeneration in acute myocardial infarction (MI). While the regenerative effects of CDCs in chronic settings have been studied extensively, little is known about how CDCs confer the cardioprotective process known as cellular postconditioning. Here, we used an in vivo rat model of ischemia/reperfusion (IR) injury–induced MI and in vitro coculture assays to investigate how CDCs protect stressed cardiomyocytes. Compared with control animals, animals that received CDCs 20 minutes after IR had reduced infarct size when measured at 48 hours. CDCs modified the myocardial leukocyte population after ischemic injury. Specifically, introduction of CDCs reduced the number of CD68+ macrophages, and these CDCs secreted factors that polarized macrophages toward a distinctive cardioprotective phenotype that was not M1 or M2. Systemic depletion of macrophages with clodronate abolished CDC-mediated cardioprotection. Using both in vitro coculture assays and a rat model of adoptive transfer after IR, we determined that CDC-conditioned macrophages attenuated cardiomyocyte apoptosis and reduced infarct size, thereby recapitulating the beneficial effects of CDC therapy. Together, our data indicate that CDCs limit acute injury by polarizing an effector macrophage population within the heart. PMID:26214527

  9. Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction.

    PubMed

    de Couto, Geoffrey; Liu, Weixin; Tseliou, Eleni; Sun, Baiming; Makkar, Nupur; Kanazawa, Hideaki; Arditi, Moshe; Marbán, Eduardo

    2015-08-03

    Ischemic injury in the heart induces an inflammatory cascade that both repairs damage and exacerbates scar tissue formation. Cardiosphere-derived cells (CDCs) are a stem-like population that is derived ex vivo from cardiac biopsies; they confer both cardioprotection and regeneration in acute myocardial infarction (MI). While the regenerative effects of CDCs in chronic settings have been studied extensively, little is known about how CDCs confer the cardioprotective process known as cellular postconditioning. Here, we used an in vivo rat model of ischemia/reperfusion (IR) injury-induced MI and in vitro coculture assays to investigate how CDCs protect stressed cardiomyocytes. Compared with control animals, animals that received CDCs 20 minutes after IR had reduced infarct size when measured at 48 hours. CDCs modified the myocardial leukocyte population after ischemic injury. Specifically, introduction of CDCs reduced the number of CD68+ macrophages, and these CDCs secreted factors that polarized macrophages toward a distinctive cardioprotective phenotype that was not M1 or M2. Systemic depletion of macrophages with clodronate abolished CDC-mediated cardioprotection. Using both in vitro coculture assays and a rat model of adoptive transfer after IR, we determined that CDC-conditioned macrophages attenuated cardiomyocyte apoptosis and reduced infarct size, thereby recapitulating the beneficial effects of CDC therapy. Together, our data indicate that CDCs limit acute injury by polarizing an effector macrophage population within the heart.

  10. Concomitant Phosphodiesterase 5 Inhibition Enhances Myocardial Protection by Inhaled Nitric Oxide in Ischemia-Reperfusion Injury.

    PubMed

    Lux, Arpad; Pokreisz, Peter; Swinnen, Melissa; Caluwe, Ellen; Gillijns, Hilde; Szelid, Zsolt; Merkely, Bela; Janssens, Stefan P

    2016-02-01

    Enhanced cyclic guanosine monophosphate (cGMP) signaling may attenuate myocardial ischemia-reperfusion injury (I/R) and improve left ventricular (LV) functional recovery after myocardial infarction (MI). We investigated the cardioprotection afforded by inhaled NO (iNO), the phosphodiesterase 5 (PDE5)-specific inhibitor tadalafil (TAD), or their combination (iNO+TAD) in C57Bl6J mice subjected to 6-minute left anterior descending artery ligation followed by reperfusion. We measured plasma and cardiac concentrations of cGMP during early reperfusion, quantified myocardial necrosis and inflammation by serial troponin-I (TnI) and myeloperoxidase-positive cell infiltration at day 3, and evaluated LV function and remodeling after 4 weeks using echocardiography and pressure-conductance catheterization. Administration of iNO, TAD, or both during I/R was safe and hemodynamically well tolerated. Compared with untreated mice (CON), only iNO+TAD increased plasma and cardiac-cGMP levels during early reperfusion (80 ± 12 versus 36 ± 6 pmol/ml and 0.15 ± 0.02 versus 0.05 ± 0.01 pmol/mg protein, P < 0.05 for both). Moreover, iNO+TAD reduced TnI at 4 hours to a greater extent (P < 0.001 versus CON) than either alone (P < 0.05 versus CON) and was associated with significantly less myocardial inflammatory cell infiltration at day 3. After 4 weeks and compared with CON, iNO+TAD was associated with increased fractional shortening (43 ± 1 versus 33 ± 2%, P < 0.01), larger stroke volumes (14.9 ± 1.2 versus 10.2 ± 0.9 μl, P < 0.05), enhanced septal and posterior wall thickening (P < 0.05 and P < 0.001, respectively), and attenuated LV dilatation (P < 0.001), whereas iNO or TAD alone conferred less benefit. Thus, iNO+TAD has superior efficacy to limit early reperfusion injury and attenuate adverse LV remodeling. Combination of inhaled NO with a long-acting PDE5 inhibitor may represent a promising strategy to reduce ischemic damage following reperfusion and better preserve LV

  11. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    PubMed Central

    Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gülay; Erdem, Özlem; Alkan, Metin; Arslan, Mustafa; Özer, Abdullah; Şivgin, Volkan; Çomu, Faruk Metin

    2015-01-01

    Objective Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion Taken together, our data indicate that

  12. Protective Effects of L-Malate against Myocardial Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Ding, Shiao; Yang, Yang; Mei, Ju

    2016-01-01

    Objective. To investigate the protective effects of L-malate against myocardial ischemia/reperfusion (I/R) injury in rats. Methods. Male Sprague-Dawley rats were randomly assigned to the following groups: sham (sham), an ischemia/reperfusion (I/R) model group (model), an DMF pretreated group (DMF), and 5 L-malate pretreated groups (15, 60, 120, 240, or 480 mg/kg, gavage) before inducing myocardial ischemia. Plasma LDH, cTn-I, TNF-α, hs-CRP, SOD, and GSH-PX were measured 3 h later I/R. Areas of myocardial infarction were measured; hemodynamic parameters during I/R were recorded. Hearts were harvested and Western blot was used to quantify Nrf2, Keap1, HO-1, and NQO-1 expression in the myocardium. Results. L-malate significantly reduced LDH and cTn-I release, reduced myocardial infarct size, inhibited expression of inflammatory cytokines, and partially preserved heart function, as well as increasing antioxidant activity after myocardial I/R injury. Western blot confirmed that L-malate reduced Kelch-like ECH-associated protein 1 in ischemic myocardial tissue, upregulated expression of Nrf2 and Nrf2 nuclear translocation, and increased expression of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1, which are major targets of Nrf2. Conclusions. L-malate may protect against myocardial I/R injury in rats and this may be associated with activation of the Nrf2/Keap1 antioxidant pathway. PMID:26941825

  13. Role of adenosine as adjunctive therapy in acute myocardial infarction.

    PubMed

    Forman, Mervyn B; Stone, Gregg W; Jackson, Edwin K

    2006-01-01

    Although early reperfusion and maintained patency is the mainstay therapy for ST elevation myocardial infarction, experimental studies demonstrate that reperfusion per se induces deleterious effects on viable ischemic cells. Thus "myocardial reperfusion injury" may compromise the full potential of reperfusion therapy and may account for unfavorable outcomes in high-risk patients. Although the mechanisms of reperfusion injury are complex and multifactorial, neutrophil-mediated microvascular injury resulting in a progressive decrease in blood flow ("no-reflow" phenomenon) likely plays an important role. Adenosine is an endogenous nucleoside found in large quantities in myocardial and endothelial cells. It activates four well-characterized receptors producing various physiological effects that attenuate many of the proposed mechanisms of reperfusion injury. The cardio-protective effects of adenosine are supported by its role as a mediator of pre- and post-conditioning. In experimental models, administration of adenosine in the peri-reperfusion period results in a marked reduction in infarct size and improvement in ventricular function. The cardioprotective effects in the canine model have a narrow time window with the drug losing its effect following three hours of ischemia. Several small clinical studies have demonstrated that administration of adenosine with reperfusion therapy reduces infarct size and improves ventricular function. In the larger AMISTAD and AMISTAD II trials a 3-h infusion of adenosine as an adjunct to reperfusion resulted in a striking reduction in infarct size (55-65%). Post hoc analysis of AMISTAD II showed that this was associated with significantly improved early and late mortality in patients treated within 3.17 h of symptoms. An intravenous infusion of adenosine for 3 h should be considered as adjunctive therapy in high risk-patients undergoing reperfusion therapy.

  14. Prostaglandin E2 reduces swine myocardial ischemia reperfusion injury via increased endothelial nitric oxide synthase and vascular endothelial growth factor expression levels

    PubMed Central

    Zhou, Ying; Yang, Peng; Li, Aili; Ye, Xiaojun; Ren, Shiyan; Li, Xianlun

    2017-01-01

    Prostaglandin E2 (PGE2) has been demonstrated to attenuate cardiac ischemia-reperfusion (I/R) injury. However, the underlying mechanism of PGE2 in cardiac I/R injury remains unknown. Upregulated expression levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) were reported in acute myocardial infarction (AMI), and were demonstrated to diminish I/R injury. In the current study the involvement of VEGF and eNOS in the myocardial protective effect of PGE2 were investigated in a catheter-based porcine model of AMI. Twenty-two Chinese miniature pigs were randomized into sham-surgery (n=6), control (n=8) and PGE2 (n=8) groups. PGE2 (1 µg/kg) was injected from 10 min prior to left anterior descending occlusion up to 1 h after reperfusion in the PGE2 group. Subsequently, the hemodynamic parameters were evaluated. Thioflavin-S and Evans Blue double staining were performed to evaluate the extent of the myocardial reperfusion area (RA) and no-reflow area (NRA). Immunohistochemical and western blot analysis were used to evaluate protein expression levels of VEGF and eNOS. Left ventricular (LV) systolic pressure significantly improved and LV end-diastolic pressure significantly decreased in the PGE2 group when compared with the control group 2 h after occlusion and 3 h after reperfusion (P<0.05, respectively). The RA and NRA were smaller in the PGE2 group than in the control group (P<0.05, respectively). Furthermore, PGE2 treatment increased the myocardial content of VEGF and eNOS when compared with the control group (P<0.05, respectively). Thus, the results of the present study demonstrate the cardio-protective mechanisms of PGE2, which may protect the heart from I/R injury via enhancement of VEGF and eNOS expression levels. PMID:28357071

  15. N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy

    PubMed Central

    Wang, Sheng; Yan, Fuxia; Wang, Tingting; He, Yi

    2017-01-01

    Background. Excessive autophagy is a major mechanism of myocardial ischemia reperfusion injury (I/RI) in diabetes with enhanced oxidative stress. Antioxidant N-acetylcysteine (NAC) reduces myocardial I/RI. It is unknown if inhibition of autophagy may represent a mechanism whereby NAC confers cardioprotection in diabetes. Methods and Results. Diabetes was induced in Sprague-Dawley rats with streptozotocin and they were treated without or with NAC (1.5 g/kg/day) for four weeks before being subjected to 30-minute coronary occlusion and 2-hour reperfusion. The results showed that cardiac levels of 15-F2t-Isoprostane were increased and that autophagy was evidenced as increases in ratio of LC3 II/I and protein P62 and AMPK and mTOR expressions were significantly increased in diabetic compared to nondiabetic rats, concomitant with increased postischemic myocardial infarct size and CK-MB release but decreased Akt and eNOS activation. Diabetes was also associated with increased postischemic apoptotic cell death manifested as increases in TUNEL positive cells, cleaved-caspase-3, and ratio of Bax/Bcl-2 protein expression. NAC significantly attenuated I/RI-induced increases in oxidative stress and cardiac apoptosis, prevented postischemic autophagy formation in diabetes, and reduced postischemic myocardial infarction (all p < 0.05). Conclusions. NAC confers cardioprotection against diabetic heart I/RI primarily through inhibiting excessive autophagy which might be a major mechanism why diabetic hearts are less tolerant to I/RI. PMID:28265179

  16. The protective effects of dexmedetomidine on liver injury-induced myocardial ischemia reperfusion.

    PubMed

    Erer, D; Ozer, A; Arslan, M; Oktar, G L; Iriz, E; Elmas, C; Zor, M H; Tatar, T; Goktas, G

    2014-01-01

    The aim of this study was to evaluate the effect of dexmedetomidine (100 µg/kg-ip) on liver injury-induced myocardial ischemia and reperfusion (IR) in rats. Twenty-four Wistar Albino rats were separated into four groups. There were four experimental groups (Group C (Control; n = 6), Group IR (ischemia-reperfusion, n = 6), Group D (Dexmedetomidine; n = 6) that underwent left thoracotomy and received ip dexmedetomidine without IR administered via 100 µg/kg ip route 30 minutes before ligating the left coronary artery, and Group IR-D (IR-Dexmedetomidine; n = 6). A small plastic snare was threaded through the ligature and placed in contact with the heart. To produce IR, a branch of the left coronary artery was occluded for 30 min followed by two hours of reperfusion. However, after the above procedure, the coronary artery was not occluded or reperfused in the control rats. At the end of the study, liver tissue was obtained for histochemical and immunohistochemical determination.Some part of tissue samples were stained with Masson-trichrome for the evaluation of ultrastructural changes and inducible nitric oxide synthase (iNOS) expression was evaluated in other part of samples for immunohistochemical examination. Histopathological changes were detected in Group IR when compared with Group C. iNOS expression was found to be increased and stronger particularly in the vascular wall, perisinusoidal space and hepatocytes around vena centralis in this group compared to the control group. Perivascular oedema was detected to be decreased in Group IR-D compared to Group IR. It was also observed that the impairment in the radial arrangement of hepatocytes significantly recovered in Group IR-D. The immunoreactivity was found to be significantly decreased in the assessment of iNOS expression in the same group when compared with Group IR. Administration of dexmedetomidine ameliorates liver injury induced by myocardial ischemia and reperfusion (Fig. 8, Ref. 33).

  17. Acute Administration of n-3 Rich Triglyceride Emulsions Provides Cardioprotection in Murine Models after Ischemia-Reperfusion

    PubMed Central

    Zirpoli, Hylde; Abdillahi, Mariane; Quadri, Nosirudeen; Ananthakrishnan, Radha; Wang, Lingjie; Rosario, Rosa; Zhu, Zhengbin; Deckelbaum, Richard J.; Ramasamy, Ravichandran

    2015-01-01

    Dietary n-3 fatty acids (FAs) may reduce cardiovascular disease risk. We questioned whether acute administration of n-3 rich triglyceride (TG) emulsions could preserve cardiac function and decrease injury after ischemia/reperfusion (I/R) insult. We used two different experimental models: in vivo, C57BL/6 mice were exposed to acute occlusion of the left anterior descending coronary artery (LAD), and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff technique (LT). In the LAD model, mice treated with n-3 TG emulsion (1.5g/kg body weight), immediately after ischemia and 1h later during reperfusion, significantly reduced infarct size and maintained cardiac function (p<0.05). In the LT model, administration of n-3 TG emulsion (300mgTG/100ml) during reperfusion significantly improved functional recovery (p<0.05). In both models, lactate dehydrogenase (LDH) levels, as a marker of injury, were significantly reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs protects hearts from I/R injury, we investigated changes in key pathways linked to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased phosphorylation of AKT and GSK3β proteins (p<0.05). Acute n-3 TG emulsion treatment also increased Bcl-2 protein level and reduced an autophagy marker, Beclin-1 (p<0.05). Additionally, cardioprotection by n-3 TG emulsion was linked to changes in PPARγ protein expression (p<0.05). Rosiglitazone and p-AKT inhibitor counteracted the positive effect of n-3 TG; GSK3β inhibitor plus n-3 TG significantly inhibited LDH release. We conclude that acute n-3 TG injection during reperfusion provides cardioprotection. This may prove to be a novel acute adjunctive reperfusion therapy after treating patients with myocardial infarction. PMID:25559887

  18. Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury.

    PubMed

    Hurt, Carl M; Lu, Yao; Stary, Creed M; Piplani, Honit; Small, Bryce A; Urban, Travis J; Qvit, Nir; Gross, Garrett J; Mochly-Rosen, Daria; Gross, Eric R

    2016-09-26

    The transient receptor potential vanilloid 1 (TRPV1) mediates cellular responses to pain, heat, or noxious stimuli by calcium influx; however, the cellular localization and function of TRPV1 in the cardiomyocyte is largely unknown. We studied whether myocardial injury is regulated by TRPV1 and whether we could mitigate reperfusion injury by limiting the calcineurin interaction with TRPV1. In primary cardiomyocytes, confocal and electron microscopy demonstrates that TRPV1 is localized to the mitochondria. Capsaicin, the specific TRPV1 agonist, dose-dependently reduced mitochondrial membrane potential and was blocked by the TRPV1 antagonist capsazepine or the calcineurin inhibitor cyclosporine. Using in silico analysis, we discovered an interaction site for TRPV1 with calcineurin. We synthesized a peptide, V1-cal, to inhibit the interaction between TRPV1 and calcineurin. In an in vivo rat myocardial infarction model, V1-cal given just prior to reperfusion substantially mitigated myocardial infarct size compared with vehicle, capsaicin, or cyclosporine (24±3% versus 61±2%, 45±1%, and 49±2%, respectively; n=6 per group; P<0.01 versus all groups). Infarct size reduction by V1-cal was also not seen in TRPV1 knockout rats. TRPV1 is localized at the mitochondria in cardiomyocytes and regulates mitochondrial membrane potential through an interaction with calcineurin. We developed a novel therapeutic, V1-cal, that substantially reduces reperfusion injury by inhibiting the interaction of calcineurin with TRPV1. These data suggest that TRPV1 is an end-effector of cardioprotection and that modulating the TRPV1 protein interaction with calcineurin limits reperfusion injury. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  19. Endovascular reperfusion therapies for acute ischemic stroke: dissecting the evidence.

    PubMed

    Tsivgoulis, Georgios; Safouris, Apostolos; Krogias, Christos; Arthur, Adam S; Alexandrov, Andrei V

    2016-05-01

    Ischemic stroke is a major cause of death and disability and intravenous thrombolysis has been the only approved acute reperfusion therapy (RT) for many years. Seven randomized-controlled clinical trials (RCTs) evaluating the safety and efficacy of endovascular therapy in patients with acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) have been recently published. These studies have changed the treatment paradigm by establishing mechanical thrombectomy (MT) as the most effective acute stroke therapy for improving functional outcome in anterior circulation ELVO with a NNT of 6. The present review will critically evaluate the results of these RCTs and of the existing meta-analyses investigating the safety and efficacy of endovascular therapy for AIS. Points of debate such as acute stroke imaging, posterior circulation stroke and general anesthesia will be addressed. We will also discuss health policies aiming to increase the availability of endovascular treatment for stroke patients.

  20. Thrombolytic Therapy, Reperfusion Phenomena, and Myocardial Recovery: Influence of Gender

    DTIC Science & Technology

    1994-05-01

    improve ventricular function, and decrease morbidity and mortality ( Braunwald , 1987). The use of thrombolytic agents, while promising to be a potential...115, 256-265. Braunwald ,E. (1987). The path to myocardial salvage by thrombolytic therapy. Circulation, 76(Suppl II), 112- 117. Brewer-Senerchia, C...A., Braunwald , E., Basta, L., Brown, E. J., Cuddy, T. E., Dagenais, G. R., Flaker, G. C., Geltman, E. M., Gersh, B. J., Goldman, S., Lamas, G. A

  1. Blood PGC-1α Concentration Predicts Myocardial Salvage and Ventricular Remodeling After ST-segment Elevation Acute Myocardial Infarction.

    PubMed

    Fabregat-Andrés, Óscar; Ridocci-Soriano, Francisco; Estornell-Erill, Jordi; Corbí-Pascual, Miguel; Valle-Muñoz, Alfonso; Berenguer-Jofresa, Alberto; Barrabés, José A; Mata, Manuel; Monsalve, María

    2015-05-01

    Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) is a metabolic regulator induced during ischemia that prevents cardiac remodeling in animal models. The activity of PGC-1α can be estimated in patients with ST-segment elevation acute myocardial infarction. The aim of the present study was to evaluate the value of blood PGC-1α levels in predicting the extent of necrosis and ventricular remodeling after infarction. In this prospective study of 31 patients with a first myocardial infarction in an anterior location and successful reperfusion, PGC-1α expression in peripheral blood on admission and at 72 hours was correlated with myocardial injury, ventricular volume, and systolic function at 6 months. Edema and myocardial necrosis were estimated using cardiac magnetic resonance imaging during the first week. At 6 months, infarct size and ventricular remodeling, defined as an increase > 10% of the left ventricular end-diastolic volume, was evaluated by follow-up magnetic resonance imaging. Myocardial salvage was defined as the difference between the edema and necrosis areas. Greater myocardial salvage was seen in patients with detectable PGC-1α levels at admission (mean [standard deviation (SD)], 18.3% [5.3%] vs 4.5% [3.9%]; P = .04). Induction of PGC-1α at 72 hours correlated with greater ventricular remodeling (change in left ventricular end-diastolic volume at 6 months, 29.7% [11.2%] vs 1.2% [5.8%]; P = .04). Baseline PGC-1α expression and an attenuated systemic response after acute myocardial infarction are associated with greater myocardial salvage and predict less ventricular remodeling. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Effects and Mechanisms of Chinese Herbal Medicine in Ameliorating Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Liu, Qing; Li, Jiqiang; Wang, Jing; Li, Jianping; Janicki, Joseph S.

    2013-01-01

    Myocardial ischemia-reperfusion (MIR) injury is a major contributor to the morbidity and mortality associated with coronary artery disease, which accounts for approximately 450,000 deaths a year in the United States alone. Chinese herbal medicine, especially combined herbal formulations, has been widely used in traditional Chinese medicine for the treatment of myocardial infarction for hundreds of years. While the efficacy of Chinese herbal medicine is well documented, the underlying molecular mechanisms remain elusive. In this review, we highlight recent studies which are focused on elucidating the cellular and molecular mechanisms using extracted compounds, single herbs, or herbal formulations in experimental settings. These studies represent recent efforts to bridge the gap between the enigma of ancient Chinese herbal medicine and the concepts of modern cell and molecular biology in the treatment of myocardial infarction. PMID:24288571

  3. Impact of microvascular obstruction on left ventricular local remodeling after reperfused myocardial infarction.

    PubMed

    Zhang, Lin; Mandry, Damien; Chen, Bailiang; Huttin, Olivier; Hossu, Gabriela; Wang, Hairong; Beaumont, Marine; Girerd, Nicolas; Felblinger, Jacques; Odille, Freddy

    2017-06-05

    To evaluate by cardiac magnetic resonance imaging (MRI) the impact of microvascular obstruction (MVO) on regional left ventricular (LV) wall characteristics and local remodeling after acute myocardial infarction (AMI). In all, 114 AMI patients underwent cardiac MRI at 3T within 2-4 days (baseline) and at 6 months (follow-up) after reperfusion. Late gadolinium enhancement and cine sequences were performed. The impact of MVO (ie, presence and extent) on regional wall thickening (WT, %), end-diastolic wall thickness (EDWT, mm), and local cavity change (mm) of LV were quantitatively analyzed. Local cavity change, calculated as surface-to-surface distance from registered endocardial surface meshes of cine imaging datasets acquired initially and at follow-up, was used to assess local remodeling. MVO was detected in 69 patients (60.5%). WT was significantly lower when MVO was present (P < 0.05); and it was inversely related to MVO transmural extent (P < 0.0001). WT improvement was significantly worsened when MVO was present in segments with infarct transmural extent exceeding 50%. Significant wall thinning occurred at follow-up in segments with infarct transmural extent >75% with further thinning by MVO presence; and EDWT decreased with increasing MVO transmural extent (P < 0.0001). LV cavity shrank in patients without MVO, whereas it dilated in those with MVO. Local cavity changes were not significantly different by a region-to-region analysis throughout the LV within each group (P = 0.57 and 0.74, respectively). MVO has a significant adverse effect on LV wall characteristics and LV remodeling. Postinfarct remodeling seems to be globally mediated rather than locally mediated during the first 6 months. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

  4. Clinical review: mechanical circulatory support for cardiogenic shock complicating acute myocardial infarction

    PubMed Central

    2010-01-01

    Acute myocardial infarction is one of the 10 leading reasons for admission to adult critical care units. In-hospital mortality for this condition has remained static in recent years, and this is related primarily to the development of cardiogenic shock. Recent advances in reperfusion therapies have had little impact on the mortality of cardiogenic shock. This may be attributable to the underutilization of life support technology that may assist or completely supplant the patient's own cardiac output until adequate myocardial recovery is established or long-term therapy can be initiated. Clinicians working in the intensive care environment are increasingly likely to be exposed to these technologies. The purpose of this review is to outline the various techniques of mechanical circulatory support and discuss the latest evidence for their use in cardiogenic shock complicating acute myocardial infarction. PMID:21067535

  5. [Primary angioplasty in acute myocardial infarct. A report on 304 consecutive patients].

    PubMed

    García y Otero, J M; Frutos Rangel, E; García García, R; Fernández Valadez, E; Zúñiga Sedano, J; Orendain González, V M; Briseño Ramírez, H

    1998-01-01

    The purpose of this study is to describe a single-center experience in primary coronary angioplasty in 304 consecutive patients with acute myocardial infarction. Sixty-seven percent were men and 33% women, the mean age was 69 years. The time from onset to treatment was 3.5 hours, 14% had previous bypass surgery and 23% prior myocardial infarction, 11% arrived in cardiogenic shock. Coronary angiography showed multivessel disease in 56% of patients, 73% had TIMI 0-1 flow. Successful PTCA occurred in 95% and in hospital mortality was 6.5%. Primary coronary angioplasty is a successful reperfusion method in acute myocardial infarction and it is associated with low mortality even in high risk groups. The rates of success and major complications in this series are similar to other publications.

  6. Ginsenoside Rg3 Improves Cardiac Function after Myocardial Ischemia/Reperfusion via Attenuating Apoptosis and Inflammation

    PubMed Central

    Zhang, Li-ping; Jiang, Yi-chuan; Yu, Xiao-feng; Xu, Hua-li; Li, Min

    2016-01-01

    Objectives. Ginsenoside Rg3 is one of the ginsenosides which are the main constituents isolated from Panax ginseng. Previous study demonstrated that ginsenoside Rg3 had a protective effect against myocardial ischemia/reperfusion- (I/R-) induced injury. Objective. This study was designed to evaluate the effect of ginsenoside Rg3 on cardiac function impairment induced by myocardial I/R in rats. Methods. Sprague-Dawley rats were subjected to myocardial I/R. Echocardiographic and hemodynamic parameters and histopathological examination were carried out. The expressions of P53, Bcl-2, Bax, and cleaved caspase-3 and the levels of TNF-α and IL-1β in the left ventricles were measured. Results. Ginsenoside Rg3 increased a left ventricular fractional shortening and left ventricular ejection fraction. Treatment with ginsenoside Rg3 also alleviated increases of left ventricular end diastolic pressure and decreases of left ventricular systolic pressure and ±dp/dt in myocardial I/R-rats. Ginsenoside Rg3 decreased apoptosis cells through inhibiting the activation of caspase-3. Ginsenoside Rg3 also caused significant reductions of the contents of TNF-α and IL-1β in left ventricles of myocardial I/R-rats. Conclusion. The findings suggested that ginsenoside Rg3 possessed the effect of improving myocardial I/R-induced cardiac function impairment and that the mechanism of pharmacological action of ginsenoside Rg3 was related to its properties of antiapoptosis and anti-inflammation. PMID:28105061

  7. Circulating NOS3 Modulates Left Ventricular Remodeling following Reperfused Myocardial Infarction

    PubMed Central

    Cortese-Krott, Miriam M.; Ohlig, Jan; Rassaf, Tienush; Gödecke, Axel; Fischer, Jens W.; Heusch, Gerd; Merx, Marc W.; Kelm, Malte

    2015-01-01

    Purpose Nitric oxide (NO) is constitutively produced and released from the endothelium and several blood cell types by the isoform 3 of the NO synthase (NOS3). We have shown that NO protects against myocardial ischemia/reperfusion (I/R) injury and that depletion of circulating NOS3 increases within 24h of ischemia/reperfusion the size of myocardial infarction (MI) in chimeric mice devoid of circulating NOS3. In the current study we hypothesized that circulating NOS3 also affects remodeling of the left ventricle following reperfused MI. Methods To analyze the role of circulating NOS3 we transplanted bone marrow of NOS3−/− and wild type (WT) mice into WT mice, producing chimerae expressing NOS3 only in vascular endothelium (BC−/EC+) or in both, blood cells and vascular endothelium (BC+/EC+). Both groups underwent 60 min of coronary occlusion in a closed-chest model of reperfused MI. During the 3 weeks post MI, structural and functional LV remodeling was serially assessed (24h, 4d, 1w, 2w and 3w) by echocardiography. At 72 hours post MI, gene expression of several extracellular matrix (ECM) modifying molecules was determined by quantitative RT-PCR analysis. At 3 weeks post MI, hemodynamics were obtained by pressure catheter, scar size and collagen content were quantified post mortem by Gomori’s One-step trichrome staining. Results Three weeks post MI, LV end-systolic (53.2±5.9μl;***p≤0.001;n = 5) and end-diastolic volumes (82.7±5.6μl;*p<0.05;n = 5) were significantly increased in BC−/EC+, along with decreased LV developed pressure (67.5±1.8mmHg;n = 18;***p≤0.001) and increased scar size/left ventricle (19.5±1.5%;n = 13;**p≤0.01) compared to BC+/EC+ (ESV:35.6±2.2μl; EDV:69.1±2.6μl n = 8; LVDP:83.2±3.2mmHg;n = 24;scar size/LV13.8±0.7%;n = 16). Myocardial scar of BC−/EC+ was characterized by increased total collagen content (20.2±0.8%;n = 13;***p≤0.001) compared to BC+/EC+ (15.9±0.5;n = 16), and increased collagen type I and III subtypes

  8. Circulating NOS3 modulates left ventricular remodeling following reperfused myocardial infarction.

    PubMed

    Gorressen, Simone; Stern, Manuel; van de Sandt, Annette M; Cortese-Krott, Miriam M; Ohlig, Jan; Rassaf, Tienush; Gödecke, Axel; Fischer, Jens W; Heusch, Gerd; Merx, Marc W; Kelm, Malte

    2015-01-01

    Nitric oxide (NO) is constitutively produced and released from the endothelium and several blood cell types by the isoform 3 of the NO synthase (NOS3). We have shown that NO protects against myocardial ischemia/reperfusion (I/R) injury and that depletion of circulating NOS3 increases within 24 h of ischemia/reperfusion the size of myocardial infarction (MI) in chimeric mice devoid of circulating NOS3. In the current study we hypothesized that circulating NOS3 also affects remodeling of the left ventricle following reperfused MI. To analyze the role of circulating NOS3 we transplanted bone marrow of NOS3-/- and wild type (WT) mice into WT mice, producing chimerae expressing NOS3 only in vascular endothelium (BC-/EC+) or in both, blood cells and vascular endothelium (BC+/EC+). Both groups underwent 60 min of coronary occlusion in a closed-chest model of reperfused MI. During the 3 weeks post MI, structural and functional LV remodeling was serially assessed (24 h, 4 d, 1 w, 2 w and 3 w) by echocardiography. At 72 hours post MI, gene expression of several extracellular matrix (ECM) modifying molecules was determined by quantitative RT-PCR analysis. At 3 weeks post MI, hemodynamics were obtained by pressure catheter, scar size and collagen content were quantified post mortem by Gomori's One-step trichrome staining. Three weeks post MI, LV end-systolic (53.2±5.9 μl; ***p≤0.001; n = 5) and end-diastolic volumes (82.7±5.6 μl; *p<0.05; n = 5) were significantly increased in BC-/EC+, along with decreased LV developed pressure (67.5±1.8 mm Hg; n = 18; ***p≤0.001) and increased scar size/left ventricle (19.5±1.5%; n = 13; **p≤0.01) compared to BC+/EC+ (ESV: 35.6±2.2 μl; EDV: 69.1±2.6 μl n = 8; LVDP: 83.2±3.2 mm Hg; n = 24; scar size/LV13.8±0.7%; n = 16). Myocardial scar of BC-/EC+ was characterized by increased total collagen content (20.2±0.8%; n = 13; ***p≤0.001) compared to BC+/EC+ (15.9±0.5; n = 16), and increased collagen type I and III subtypes

  9. Protective effect of bradykinin antagonist Hoe-140 during in vivo myocardial ischemic-reperfusion injury in the cat.

    PubMed

    Kumari, Rashmi; Maulik, Mohua; Manchanda, Subhash Chandra; Maulik, Subir Kumar

    2003-10-15

    The effect of icatibant (Hoe-140), a selective bradykinin receptor (B(2)) antagonist on myocardial ischemic-reperfusion injury was studied in open chest barbiturate anaesthetized cats. The left anterior descending coronary artery was occluded for 15 min, followed by 60 min of reperfusion. Saline or icatibant (200 microg/kg) was administered intravenously slowly over 2 min, 5 min before reperfusion. In the saline-treated group, myocardial ischemic-reperfusion injury was evidenced by depressed MAP, depressed peak positive and negative dP/dt and elevated left ventricular end-diastolic pressure and enhanced oxidative stress [elevated plasma thiobarbituric acid reactive substances (TBARS; a marker for lipid peroxidation), depressed myocardial GSH (reduced glutathione), superoxide dismutase (SOD), catalase] and depletion of adenosine triphosphate (ATP) along with rise in plasma creatine phosphokinase (CPK). Administration of icatibant resulted in complete hemodynamic recovery together with repletion of ATP and reduction in plasma TBARS without any significant change in myocardial SOD, catalase and GSH. The results of the present study suggest a protective role of icatibant in myocardial ischemic-reperfusion injury.

  10. Reduction of myocardial ischemia reperfusion injury with regular consumption of grapes.

    PubMed

    Cui, Jianhua; Cordis, Gerald A; Tosaki, Arpad; Maulik, Nilanjana; Das, Dipak K

    2002-05-01

    Recently several polyphenolic antioxidants derived from grape seeds and skins have been implicated in cardioprotection. This study was undertaken to determine if the grapes were equally cardioprotective. Sprague Dawley male rats were given (orally) standardized grape extract (SGE) for a period of three weeks. Time-matched control experiments were performed by feeding the animals 45 microg/100 of glucose plus 45 microg/100 g fructose per day for three weeks. After 30 days, rats were sacrificed, hearts excised and perfused via working-mode. Hearts were made ischemic for 30 min followed by two hours of reperfusion. At 100 mg/kg and at 200 mg/kg, SGE provided significant cardioprotection as evidenced by improved post-ischemic ventricular recovery and reduced amount of myocardial infarction. No cardioprotection was apparent when rats were given grape samples at a dose of 50 mg/100 g/day. In vitro studies demonstrated that the SGE could directly scavenge superoxide and hydroxyl radicals which are formed in the ischemic reperfused myocardium. The results demonstrate that the heats of the rats fed SGE reduced myocardial ischemia reperfusion injury by functioning as in vivo antioxidant.

  11. Myocardial contrast echocardiography to assess perfusion in a mouse model of ischemia/reperfusion injury

    NASA Astrophysics Data System (ADS)

    Hossack, John A.; Li, Yinbo; Christensen, Jonathan P.; Yang, Zequan; French, Brent A.

    2004-04-01

    Noninvasive approaches for measuring anatomical and physiological changes resulting from myocardial ischemia / reperfusion injury in the mouse heart have significant value since the mouse provides a practical, low-cost model for modeling human heart disease. In this work, perfusion was assessed before, during and after an induced closed- chest, coronary ischemic event. Ultrasound contrast agent, similar to MP1950, in a saline suspension, was injected via cannulated carotid artery as a bolus and imaged using a Siemens Sequoia 512 scanner and a 15L8 intraoperative transducer operating in second harmonic imaging mode. Image sequences were transferred from the scanner to a PC for analysis. Regions of interest were defined in septal and anterior segments of the myocardium. During the ischemic event, when perfusion was diminished in the anterior segment, mean video intensity in the affected segment was reduced by one half. Furthermore, following reperfusion, hyperemia (enhanced blood flow) was observed in the anterior segment. Specifically, the mean video intensity in the affected segment was increased by approximately 50% over the original baseline level prior to ischemia. Following the approach of Kaul et al., [1], gamma variate curves were fitted to the time varying level of mean video intensity. This foundation suggests the possibility of quantifying myocardial blood flow in ischemic regions of a mouse heart using automated analysis of contrast image data sets. An improved approach to perfusion assessment using the destruction-reperfusion approach [2] is also presented.

  12. Evaluation of TRPM (transient receptor potential melastatin) genes expressions in myocardial ischemia and reperfusion.

    PubMed

    Demir, Tuncer; Yumrutas, Onder; Cengiz, Beyhan; Demiryurek, Seniz; Unverdi, Hatice; Kaplan, Davut Sinan; Bayraktar, Recep; Ozkul, Nadide; Bagcı, Cahit

    2014-05-01

    In the present study, the expression levels of TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, and TRPM8 genes were evaluated in heart tissues after ischemia/reperfusion (IR). For this study, 30 albino male Wistar rats were equally divided into three groups as follows: Group 1: control group (n:10), Group II: ischemia group (ischemia for 60 min) (n:10) and Group III: IR (reperfusion 48 h after ischemia for 60 min and reperfusion for 48 h). The expression levels of the TRPM genes were analyzed by semi-quantitative reverse transcriptase-PCR. When compared to the ischemia control, the expression levels of TRPM2, TRPM4, and TRPM6 did not change, whereas that of TRPM7 increased. However, TRPM1, TRPM3, TRPM5, and TRPM8 were not expressed in heart tissue. Histopathological analysis of the myocardial tissues showed that the structures that were most damaged were those exposed to IR. The findings showed that there is a positive relationship between TRPM7 expression and myocardial IR injury.

  13. GUSTO V: combination drug treatment of acute myocardial infarction. Global Use of Strategies to Open Occluded Coronary Arteries.

    PubMed

    Askari, Arman T; Lincoff, A Michael

    2002-07-01

    The combination of abciximab in full doses and reteplase in half doses did not significantly reduce the rate of mortality at 30 days in patients with acute ST-segment elevation myocardial infarction (MI) when compared with reteplase in full doses in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO V) trial. However, subgroup analysis indicates that the combined regimen reduced the complications of acute MI, representing an important alternative strategy for pharmacologic reperfusion.

  14. Efficacy of an Embolic Protection Stent as a Function of Delay to Reperfusion in ST-Segment Elevation Myocardial Infarction (from the MASTER Trial).

    PubMed

    Dudek, Dariusz; Brener, Sorin J; Rakowski, Tomasz; Dziewierz, Artur; Abizaid, Alexandre; Silber, Sigmund; Yaacoby, Elad; Dizon, José M; Costa, Ricardo A; Maehara, Akiko; Dressler, Ovidiu; Stone, Gregg W

    2014-11-15

    The ability of stent implantation to improve indexes of reperfusion may depend on the time to reperfusion in acute ST-segment elevation myocardial infarction (STEMI) and may also vary with stent type. The purpose of this prespecified analysis from the randomized MGUARD for Acute ST Elevation Reperfusion trial was to evaluate the impact of delay to reperfusion on outcomes in patients with STEMI undergoing primary percutaneous coronary intervention with the MGuard embolic protection stent or standard metallic stents. A total of 431 patients were divided according to symptom-onset-to-balloon time (SBT) into 2 groups: SBT ≤3 hours (167 patients; 39%) and SBT >3 hours (264 patients; 61%). Complete ST-segment resolution (STR) after percutaneous coronary intervention was more often achieved in patients with shorter SBT (58.6% vs 47%, p = 0.02). At 1 year, the all-cause mortality rate was lower in patients with shorter SBT (0% vs 3.5%, p = 0.02). STR was achieved in 58% of MGuard patients and in 45% of the control stent patients (p = 0.008). STR was 57% in the MGuard group versus 38% in the control group (p = 0.002 for SBT >3 hours) and 60% versus 57% (p = 0.72), respectively, for SBT ≤3 hours (p for interaction = 0.11). In conclusion, longer delay to mechanical reperfusion remains an important factor negatively influencing outcomes in patients with STEMI. Use of the MGuard embolic protection stent compared with conventional metallic stents resulted in superior rates of complete STR, even in patients with longer delays to reperfusion.

  15. Decreased selenium levels in acute myocardial infarction

    SciTech Connect

    Kok, F.J.; Hofman, A.; Witteman, J.C.M.; de Bruijn, A.M.; Kruyssen, D.H.C.M.; de Bruin, M.; Valkenburg, H.A. )

    1989-02-24

    To study the association between selenium status and the risk of myocardial infarction, the authors compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls. Because toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event.

  16. [Methylphenidate induced ST elevation acute myocardial infarction].

    PubMed

    Ruwald, Martin Huth; Ruwald, Anne-Christine Huth; Tønder, Niels

    2012-03-05

    Adult attention deficit and hyperkinetic disorder (ADHD) is increasingly diagnosed and treated with methylphenidate. We present the case of an 20 year-old man, who was diagnosed with ADHD and suffered a ST elevation acute myocardial infarction due to coronary vasospasm related to an overdose, and subsequent episodes of myocardial injury due to the use and misuse of methylphenidate over a period of two years. We recommend an increased attention to the subscription of methylphenidate to patients, who are at risk of misuse and patients, who have a cardiovascular history.

  17. Aspergillus coronary embolization causing acute myocardial infarction.

    PubMed

    Laszewski, M; Trigg, M; de Alarcon, P; Giller, R

    1988-05-01

    An increased frequency of disseminated aspergillosis has been observed in the last decade, mostly occurring in immunocompromised patients including the bone marrow transplant population. Cardiac involvement by Aspergillus remains rare. We report the clinical and postmortem findings of an unusual case of Aspergillus pancarditis in a 7-year-old bone marrow transplant patient with Aspergillus embolization to the coronary arteries leading to a massive acute myocardial infarction. This case suggests that myocardial injury secondary to disseminated aspergillosis should be included in the differential diagnosis of chest pain in the immunocompromised pediatric patient.

  18. [Frovatriptan possibly causing acute myocardial infarction].

    PubMed

    Møller-Helgestad, Ole Kristian; Kaltoft, Anne Kjer; Kasch, Helge

    2015-03-23

    Globally migraine affects more than 10% of the adult population and it is treated with simple analgesics, combined with a triptan for a stronger treatment effect. Triptans cause arterial vasoconstriction, and this is a case report of vasospasm-induced acute myocardial infarction in a 61-year-old woman with frequent episodic migraine attacks treated with triptans. She was possibly also suffering from medication overuse headache. We suggest that regular frovatriptan use may have contributed to the myocardial infarction and that long-term triptan use may have caused the medication overuse headache.

  19. Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI).

    PubMed

    Siddiqi, Nishat; Neil, Christopher; Bruce, Margaret; MacLennan, Graeme; Cotton, Seonaidh; Papadopoulou, Sofia; Feelisch, Martin; Bunce, Nicholas; Lim, Pitt O; Hildick-Smith, David; Horowitz, John; Madhani, Melanie; Boon, Nicholas; Dawson, Dana; Kaski, Juan Carlos; Frenneaux, Michael

    2014-05-14

    Despite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this double-blind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI). A total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6-8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6-8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size -0.7% 95% CI: -2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6-8 days and at 6 months and final infarct size (FIS) measured at 6 months. Sodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

  20. Protein methionine oxidation augments reperfusion injury in acute ischemic stroke

    PubMed Central

    Gu, Sean X.; Blokhin, Ilya O.; Wilson, Katina M.; Dhanesha, Nirav; Doddapattar, Prakash; Grumbach, Isabella M.; Chauhan, Anil K.; Lentz, Steven R.

    2016-01-01

    Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII). In a murine model, MsrA deficiency resulted in increased NF-κB activation and neutrophil infiltration, larger infarct volumes, and more severe neurological impairment after transient cerebral ischemia/reperfusion injury. This phenotype was prevented by inhibition of NF-κB or CaMKII. MsrA-deficient mice also exhibited enhanced leukocyte rolling and upregulation of E-selectin, an endothelial NF-κB–dependent adhesion molecule known to contribute to neurovascular inflammation in ischemic stroke. Finally, bone marrow transplantation experiments demonstrated that the neuroprotective effect was mediated by MsrA expressed in nonhematopoietic cells. These findings suggest that protein methionine oxidation in nonmyeloid cells is a key mechanism of postischemic oxidative injury mediated by NF-κB activation, leading to neutrophil recruitment and neurovascular inflammation in acute ischemic stroke. PMID:27294204

  1. Clinical value of delayed thallium-201 myocardial imaging in suspected acute myocardial infarction.

    PubMed Central

    McKillop, J H; Turner, J G; Gray, H W; Bessent, R G; Greig, W R

    1978-01-01

    Fifty patients with acute chest pain had thallium-201 myocardial imaging performed three to six days after emergency admission to hospital. The image was abnormal in 20 out of 22 patients with acute transmural myocardial infarcts but in only 1 of 5 with acute subendocardial infarcts. Indistinguishable scan abnormalities caused by old infarcts were seen in 7 patients, and caused by myocardial ischaemia in 1 patient. A single thallium-201 myocardial scan some days after the onset of symptoms appears to be of little value in the clinical assessment of patients with suspected acute myocardial infarction. Images PMID:687488

  2. Febuxostat pretreatment attenuates myocardial ischemia/reperfusion injury via mitochondrial apoptosis.

    PubMed

    Wang, Shulin; Li, Yunpeng; Song, Xudong; Wang, Xianbao; Zhao, Cong; Chen, Aihua; Yang, Pingzhen

    2015-07-02

    Febuxostat is a selective inhibitor of xanthine oxidase (XO). XO is a critical source of reactive oxygen species (ROS) during myocardial ischemia/reperfusion (I/R) injury. Inhibition of XO is therapeutically effective in I/R injury. Evidence suggests that febuxostat exerts antioxidant effects by directly scavenging ROS. The present study was performed to investigate the effects of febuxostat on myocardial I/R injury and its underlying mechanisms. We utilized an in vivo mouse model of myocardial I/R injury and an in vitro neonatal rat cardiomyocyte (NRC) model of hypoxia/reoxygenation (H/R) injury. Mice were randomized into five groups: Sham, I/R (I/R + Vehicle), I/R + FEB (I/R + febuxostat), AL + I/R (I/R + allopurinol) and FEB (febuxostat), respectively. The I/R + FEB mice were pretreated with febuxostat (5 mg/kg; i.p.) 24 and 1 h prior to I/R. NRCs received febuxostat (1 and 10 µM) at 24 and 1 h before exposure to hypoxia for 3 h followed by reoxygenation for 3 h. Cardiac function, myocardial infarct size, serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), and myocardial apoptotic index (AI) were measured in order to ascertain the effects of febuxostat on myocardial I/R injury. Hypoxia/reperfusion (H/R) injury in NRCs was examined using MTT, LDH leakage assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The underlying mechanisms were determined by measuring ROS production, mitochondrial membrane potential (ΔΨm), and expression of cytochrome c, cleaved caspases as well as Bcl-2 protein levels. Myocardial I/R led to an elevation in the myocardial infarct size, serum levels of CK and LDH, cell death and AI. Furthermore, I/R reduced cardiac function. These changes were significantly attenuated by pretreatment with febuxostat and allopurinol, especially by febuxostat. Febuxostat also protected the mitochondrial structure following myocardial I/R, inhibited H/R-induced ROS generation, stabilized the

  3. Hypercholesterolemia aggravates myocardial ischemia reperfusion injury via activating endoplasmic reticulum stress-mediated apoptosis.

    PubMed

    Wu, Nan; Zhang, Xiaowen; Jia, Pengyu; Jia, Dalin

    2015-12-01

    The effect of hypercholesterolemia on myocardial ischemia reperfusion injury (MIRI) is in controversy and the underlying mechanism is still not well understood. In the present study, we firstly detected the effects of hypercholesterolemia on MIRI and the role of endoplasmic reticulum (ER) stress-mediated apoptosis pathway in this process. The infarct size was determined by TTC staining, and apoptosis was measured by the TUNEL method. The marker proteins of ER stress response and ER stress-mediated apoptosis pathway were detected by Western blot. The results showed that high cholesterol diet-induced hypercholesterolemia significantly increased the myocardial infarct size, the release of myocardium enzyme and the ratio of apoptosis, but did not affect the recovery of cardiac function. Moreover, hypercholesterolemia also remarkably up-regulated the expressions of ER stress markers (glucose-regulated protein 78 and calreticulin) and critical molecules in ER stress-mediated apoptosis pathway (CHOP, caspase 12, phospho-JNK). In conclusion, our study demonstrated that hypercholesterolemia enhanced myocardial vulnerability/sensitivity to ischemia reperfusion injury involved in aggravation the ER stress and activation of ER stress-mediated apoptosis pathway and it gave us a new insight into the underlying mechanisms associated with hypercholesterolemia-induced exaggerated MIRI and also provided a novel target for preventing MIRI in the presence of hypercholesterolemia. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Ginsenoside Rd mitigates myocardial ischemia-reperfusion injury via Nrf2/HO-1 signaling pathway

    PubMed Central

    Zeng, Xiaofeng; Li, Juan; Li, Zhen

    2015-01-01

    Ginsenoside Rd (GsRd) reportedly protects the heart against ischemia-reperfusion (I/R) injury. Nrf2/HO-1 signaling plays a key role in attenuating oxidative stress. However, it remains unclear whether GsRd protects against myocardial I/R injury via Nrf2/HO-1 signaling. This study aimed to investigate the role of Nrf2/HO-1 signaling in the cardioprotective effect of GsRd. Rats received 30 min ischemia followed by 2 h reperfusion. Cardiac function, infarct size and serum CK, LDH, cTnI levels were detected. The expression of Nrf2 and HO-1 was detected by western blot. The results suggested that GsRd attenuated myocardial I/R injury as evidenced by improved cardiac function, decreased infarct size and decreased levels of serum CK, LDH and cTnI. In addition, GsRd administration enhanced the expression of Nrf2 and HO-1. In conclusion, the present study shows that GsRd protects against myocardial I/R injury via Nrf2/HO-1 signaling. PMID:26550440

  5. Myocardial ischemia-reperfusion enhances transcriptional expression of endothelin-1 and vasoconstrictor ETB receptors via the protein kinase MEK-ERK1/2 signaling pathway in rat

    PubMed Central

    Kruse, Lars Schack; Berchtold, Lukas Adrian; Grell, Anne-Sofie; Warfvinge, Karin; Edvinsson, Lars

    2017-01-01

    Background Coronary artery remodelling and vasospasm is a complication of acute myocardial ischemia and reperfusion. The underlying mechanisms are complex, but the vasoconstrictor peptide endothelin-1 is suggested to have an important role. This study aimed to determine whether the expression of endothelin-1 and its receptors are regulated in the myocardium and in coronary arteries after experimental ischemia-reperfusion. Furthermore, we evaluated whether treatment with a specific MEK1/2 inhibitor, U0126, modified the expression and function of these proteins. Methods and findings Sprague-Dawley rats were randomly divided into three groups: sham-operated, ischemia-reperfusion with vehicle treatment and ischemia-reperfusion with U0126 treatment. Ischemia was induced by ligating the left anterior descending coronary artery for 30 minutes followed by reperfusion. U0126 was administered before ischemia and repeated 6 hours after start of reperfusion. The contractile properties of isolated coronary arteries to endothelin-1 and sarafotoxin 6c were evaluated using wire-myography. The gene expression of endothelin-1 and endothelin receptors were measured using qPCR. Distribution and localization of proteins (pERK1/2, prepro-endothelin-1, endothelin-1, and endothelin ETA and ETB receptors) were analysed by Western blot and immunohistochemistry. We found that pERK1/2 was significantly augmented in the ischemic area 3 hours after ischemia-reperfusion; this correlated with increased ETB receptor and ET-1 gene expressions in ischemic myocardium and in coronary arteries. ETB receptor-mediated vasoconstriction was observed to be increased in coronary arteries 24 hours after ischemia-reperfusion. Treatment with U0126 reduced pERK1/2, expression of ET-1 and ETB receptor, and ETB receptor-mediated vasoconstriction. Conclusions These findings suggest that the MEK-ERK1/2 signaling pathway is important for regulating endothelin-1 and ETB receptors in myocardium and coronary arteries

  6. Neuroendocrine activation after acute myocardial infarction.

    PubMed Central

    McAlpine, H M; Morton, J J; Leckie, B; Rumley, A; Gillen, G; Dargie, H J

    1988-01-01

    The extent of neuroendocrine activation, its time course, and relation to left ventricular dysfunction and arrhythmias were investigated in 78 consecutive patients with suspected acute myocardial infarction. High concentrations of arginine vasopressin were found within six hours of symptoms, even in the absence of myocardial infarction (n = 18). Plasma catecholamine concentrations also were highest on admission, whereas renin and angiotensin II concentrations rose progressively over the first three days, not only in those with heart failure but also in patients with no clinical complications. Heart failure, ventricular tachycardia, and deaths were associated with extensive myocardial infarction, low left ventricular ejection fraction, and persistently high concentrations of catecholamines, renin, and angiotensin II up to 10 days after admission, whereas in uncomplicated cases concentrations had already returned to normal. PMID:3415870

  7. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury.

    PubMed

    Kawaguchi, Masanori; Takahashi, Masafumi; Hata, Takeki; Kashima, Yuichiro; Usui, Fumitake; Morimoto, Hajime; Izawa, Atsushi; Takahashi, Yasuko; Masumoto, Junya; Koyama, Jun; Hongo, Minoru; Noda, Tetsuo; Nakayama, Jun; Sagara, Junji; Taniguchi, Shun'ichiro; Ikeda, Uichi

    2011-02-15

    Background- Inflammation plays a key role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury; however, the mechanism by which myocardial I/R induces inflammation remains unclear. Recent evidence indicates that a sterile inflammatory response triggered by tissue damage is mediated through a multiple-protein complex called the inflammasome. Therefore, we hypothesized that the inflammasome is an initial sensor for danger signal(s) in myocardial I/R injury. Methods and Results- We demonstrate that inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, is crucially involved in the initial inflammatory response after myocardial I/R injury. We found that inflammasomes are formed by I/R and that its subsequent activation of inflammasomes leads to interleukin-1β production, resulting in inflammatory responses such as inflammatory cell infiltration and cytokine expression in the heart. In mice deficient for apoptosis-associated speck-like adaptor protein and caspase-1, these inflammatory responses and subsequent injuries, including infarct development and myocardial fibrosis and dysfunction, were markedly diminished. Bone marrow transplantation experiments with apoptosis-associated speck-like adaptor protein-deficient mice revealed that inflammasome activation in bone marrow cells and myocardial resident cells such as cardiomyocytes or cardiac fibroblasts plays an important role in myocardial I/R injury. In vitro experiments revealed that hypoxia/reoxygenation stimulated inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, and that hypoxia/reoxygenation-induced activation was mediated through reactive oxygen species production and potassium efflux. Conclusions- Our results demonstrate the molecular basis for the initial inflammatory response after I/R and suggest that the inflammasome is a potential novel therapeutic target for preventing myocardial I/R injury.

  8. Importance of tissue perfusion in ST segment elevation myocardial infarction patients undergoing reperfusion strategies: role of adenosine.

    PubMed

    Forman, Mervyn B; Jackson, Edwin K

    2007-11-01

    High risk ST segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy continue to exhibit significant morbidity and mortality due in part to myocardial reperfusion injury. Importantly, preclinical studies demonstrate that progressive microcirculatory failure (the "no-reflow" phenomenon) contributes significantly to myocardial reperfusion injury. Diagnostic techniques to measure tissue perfusion have validated this concept in humans, and it is now clear that abnormal tissue perfusion occurs frequently in STEMI patients undergoing reperfusion therapy. Moreover, because tissue perfusion correlates poorly with epicardial blood flow (TIMI flow grade), clinical studies show that tissue perfusion is an independent predictor of early and late mortality in STEMI patients and is associated with infarct size, ventricular function, CHF and ventricular arrhythmias. The mechanisms responsible for abnormal tissue perfusion are multifactorial and include both mechanical obstruction and vasoconstrictor humoral factors. Adenosine, an endogenous nucleoside, maintains microcirculatory flow following reperfusion by activating four well-characterized extracellular receptors. Because activation of adenosine receptors attenuates the mechanical and functional mechanisms leading to the "no reflow" phenomenon and activates other cardioprotective pathways as well, it is not surprising that both experimental and clinical studies show striking myocardial salvage with intravenous infusions of adenosine administered in the peri-reperfusion period. For example, a post hoc analysis of the AMISTAD II trial indicates a significant reduction in 1 and 6-month mortality in STEMI patients undergoing reperfusion therapy who are treated with adenosine within 3 hours of symptoms. In conclusion, adenosine's numerous cardioprotective effects, including attenuation of the "no-reflow" phenomenon, support its use in high risk STEMI undergoing reperfusion.

  9. Effects of propofol on myocardial ischemia-reperfusion injury in rats with type-2 diabetes mellitus

    PubMed Central

    Wang, Ying; Qi, Xiuru; Wang, Chunliang; Zhao, Danning; Wang, Hongjie; Zhang, Jianxin

    2017-01-01

    The current study aimed to examine the effects of propofol on myocardial ischemia-reperfusion injury (MIRI) in rats with type-2 diabetes mellitus (T2DM) and to assess the role of inflammatory mediators. Fifty healthy male adult Sprague-Dawley rats were randomly divided into the sham, ischemia-reperfusion (IR), IR plus low, middle and high-dose (6, 12 and 24 mg/kg/h, intravenous) propofol groups. The rats of all the groups were fed a high-sugar and high-fat diet for 8 weeks and streptozotocin (30 mg/kg, intraperitoneally) was used to establish the T2DM model. Apart from the sham group rats, MIRI was induced by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 2 h. Heart rate (HR), left ventricular systolic pressure (LVSP), and the rate of left ventricular pressure increase in early systole (± dp/dtmax) were recorded. Levels of cardiac troponin T (cTnT), nitric oxide (NO), endothelin-1 (ET-1), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured. Myocardial lesions were observed under light microscopy and scanning electron microscopy. Compared with levels prior to arterial occlusion, HR, LVSP, and ± dp/dtmax were significantly reduced (P<0.05) following occlusion for 30 min and reperfusion for 2 h. The administration of propofol ameliorated the cardiac function of rats as reflected by the increase in HR, LVSP and ± dp/dtmax. In addition, the administration of propofol increased the serum NO concentration, and reduced ET-1 and cTnT levels, as well as levels of inflammatory mediators including IL-1β, IL-6 and TNF-α. Thus, propofol exerts protective effects against MIRI in T2DM rats by increasing NO and reducing ET-1 and the inflammatory mediators. PMID:28123710

  10. Effects of propofol on myocardial ischemia-reperfusion injury in rats with type-2 diabetes mellitus.

    PubMed

    Wang, Ying; Qi, Xiuru; Wang, Chunliang; Zhao, Danning; Wang, Hongjie; Zhang, Jianxin

    2017-01-01

    The current study aimed to examine the effects of propofol on myocardial ischemia-reperfusion injury (MIRI) in rats with type-2 diabetes mellitus (T2DM) and to assess the role of inflammatory mediators. Fifty healthy male adult Sprague-Dawley rats were randomly divided into the sham, ischemia-reperfusion (IR), IR plus low, middle and high-dose (6, 12 and 24 mg/kg/h, intravenous) propofol groups. The rats of all the groups were fed a high-sugar and high-fat diet for 8 weeks and streptozotocin (30 mg/kg, intraperitoneally) was used to establish the T2DM model. Apart from the sham group rats, MIRI was induced by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 2 h. Heart rate (HR), left ventricular systolic pressure (LVSP), and the rate of left ventricular pressure increase in early systole (± dp/dtmax) were recorded. Levels of cardiac troponin T (cTnT), nitric oxide (NO), endothelin-1 (ET-1), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured. Myocardial lesions were observed under light microscopy and scanning electron microscopy. Compared with levels prior to arterial occlusion, HR, LVSP, and ± dp/dtmax were significantly reduced (P<0.05) following occlusion for 30 min and reperfusion for 2 h. The administration of propofol ameliorated the cardiac function of rats as reflected by the increase in HR, LVSP and ± dp/dtmax. In addition, the administration of propofol increased the serum NO concentration, and reduced ET-1 and cTnT levels, as well as levels of inflammatory mediators including IL-1β, IL-6 and TNF-α. Thus, propofol exerts protective effects against MIRI in T2DM rats by increasing NO and reducing ET-1 and the inflammatory mediators.

  11. Association Between Acidosis Soon After Reperfusion and Contrast-Induced Nephropathy in Patients With a First-Time ST-Segment Elevation Myocardial Infarction.

    PubMed

    Gohbara, Masaomi; Hayakawa, Azusa; Akazawa, Yusuke; Furihata, Shuta; Kondo, Ai; Fukushima, Yusuke; Tomari, Sakie; Endo, Tsutomu; Kimura, Kazuo; Tamura, Kouichi

    2017-08-23

    Contrast-induced nephropathy (CIN) is associated with poor outcomes in patients with acute myocardial infarction. However, the predictors of CIN have yet to be fully elucidated. The study included 273 consecutive patients with a first-time ST-segment elevation myocardial infarction who underwent reperfusion within 12 hours of symptom onset. The exclusion criteria were hemodialysis, mechanical ventilation, or previous coronary artery bypass grafting. All patients underwent arterial blood gas analysis soon after reperfusion. CIN was defined as an increase of 0.5 mg/dL in serum creatinine or a 25% increase from baseline between 48 and 72 hours after contrast medium exposure. Acidosis was defined as an arterial blood pH <7.35. CIN was observed in 35 patients (12.8%). Multivariable logistic regression analysis with forward stepwise algorithm revealed a significant association between CIN and the following: reperfusion time, the prevalence of hypertension, peak creatine kinase-MB, high-sensitivity C-reactive protein on admission, and the incidence of acidosis (P<0.05). Multivariable logistic regression analysis revealed that the incidence of acidosis was associated with CIN when adjusted for age, male sex, body mass index, amount of contrast medium used, estimated glomerular filtration rate on admission, glucose level on admission, high-sensitivity C-reactive protein on admission, and left ventricular ejection fraction (P<0.05). Moreover, the incidence of acidosis was associated with CIN when adjusted for the Mehran CIN risk score (odds ratio: 2.229, P=0.049). The incidence of acidosis soon after reperfusion was associated with CIN in patients with a first-time ST-segment elevation myocardial infarction. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  12. Myocardial ischemia, reperfusion, and infarction in chronically instrumented, intact, conscious, and unrestrained mice

    PubMed Central

    Lujan, Heidi L.; Janbaih, Hussein; Feng, Han-Zhong; Jin, Jian-Ping

    2012-01-01

    In the United States alone, the National Heart, Lung, and Blood Institute (NHLBI) has invested several hundred million dollars in pursuit of myocardial infarct-sparing therapies. However, due largely to methodological limitations, this investment has not produced any notable clinical application or cardioprotective therapy. Among the major methodological limitations is the reliance on animal models that do not mimic the clinical situation. In this context, the limited use of conscious animal models is of major concern. In fact, whenever possible, studies of cardiovascular physiology and pathophysiology should be conducted in conscious, complex models to avoid the complications associated with the use of anesthesia and surgical trauma. The mouse has significant advantages over other experimental models for the investigation of infarct-sparing therapies. The mouse is inexpensive, has a high throughput, and presents the ability of one to create genetically modified models. However, successful infarct-sparing therapies in anesthetized mice or isolated mouse hearts may not be successful in more complex models, including conscious mice. Accordingly, a conscious mouse model of myocardial ischemia and reperfusion has the potential to be of major importance for advancing the concepts and methods that drive the development of infarct-sparing therapies. Therefore, we describe, for the first time, the use of an intact, conscious, and unrestrained mouse model of myocardial ischemia-reperfusion and infarction. The conscious mouse model permits occlusion and reperfusion of the left anterior descending coronary artery in an intact, complex model free of the confounding influences of anesthetics and surgical trauma. This methodology may be adopted for advancing the concepts and ideas that drive cardiovascular research. PMID:22538514

  13. Myocardial ischemia, reperfusion, and infarction in chronically instrumented, intact, conscious, and unrestrained mice.

    PubMed

    Lujan, Heidi L; Janbaih, Hussein; Feng, Han-Zhong; Jin, Jian-Ping; DiCarlo, Stephen E

    2012-06-15

    In the United States alone, the National Heart, Lung, and Blood Institute (NHLBI) has invested several hundred million dollars in pursuit of myocardial infarct-sparing therapies. However, due largely to methodological limitations, this investment has not produced any notable clinical application or cardioprotective therapy. Among the major methodological limitations is the reliance on animal models that do not mimic the clinical situation. In this context, the limited use of conscious animal models is of major concern. In fact, whenever possible, studies of cardiovascular physiology and pathophysiology should be conducted in conscious, complex models to avoid the complications associated with the use of anesthesia and surgical trauma. The mouse has significant advantages over other experimental models for the investigation of infarct-sparing therapies. The mouse is inexpensive, has a high throughput, and presents the ability of one to create genetically modified models. However, successful infarct-sparing therapies in anesthetized mice or isolated mouse hearts may not be successful in more complex models, including conscious mice. Accordingly, a conscious mouse model of myocardial ischemia and reperfusion has the potential to be of major importance for advancing the concepts and methods that drive the development of infarct-sparing therapies. Therefore, we describe, for the first time, the use of an intact, conscious, and unrestrained mouse model of myocardial ischemia-reperfusion and infarction. The conscious mouse model permits occlusion and reperfusion of the left anterior descending coronary artery in an intact, complex model free of the confounding influences of anesthetics and surgical trauma. This methodology may be adopted for advancing the concepts and ideas that drive cardiovascular research.

  14. Effect of Curcuma longa and Ocimum sanctum on myocardial apoptosis in experimentally induced myocardial ischemic-reperfusion injury

    PubMed Central

    Mohanty, Ipseeta; Arya, Dharamvir Singh; Gupta, Suresh Kumar

    2006-01-01

    Background In the present investigation, the effect of Curcuma longa (Cl) and Ocimum sanctum (Os) on myocardial apoptosis and cardiac function was studied in an ischemia and reperfusion (I-R) model of myocardial injury. Methods Wistar albino rats were divided into four groups and orally fed saline once daily (sham, control IR) or Cl (100 mg/kg; Cl-IR) or Os (75 mg/kg; Os-IR) respectively for 1 month. On the 31st day, in the rats of the control IR, Cl-IR and Os-IR groups LAD occlusion was undertaken for 45 min, and reperfusion was allowed for 1 h. The hemodynamic parameters{mean arterial pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak positive (+) LVdP/dt (rate of pressure development) and negative (-) LVdP/dt (rate of pressure decline)} were monitored at pre-set points throughout the experimental duration and subsequently, the animals were sacrificed for immunohistopathological (Bax, Bcl-2 protein expression & TUNEL positivity) and histopathological studies. Results Chronic treatment with Cl significantly reduced TUNEL positivity (p < 0.05), Bax protein (p < 0.001) and upregulated Bcl-2 (p < 0.001) expression in comparison to control IR group. In addition, Cl demonstrated mitigating effects on several myocardial injury induced hemodynamic {(+)LVdP/dt, (-) LVdP/dt & LVEDP} and histopathological perturbations. Chronic Os treatment resulted in modest modulation of the hemodynamic alterations (MAP, LVEDP) but failed to demonstrate any significant antiapoptotic effects and prevent the histopathological alterations as compared to control IR group. Conclusion In the present study, significant cardioprotection and functional recovery demonstrated by Cl may be attributed to its anti-apoptotic property. In contrast to Os, Cl may attenuate cell death due to apoptosis and prevent the impairment of cardiac performance. PMID:16504000

  15. Intracoronary hypothermia for acute myocardial infarction in the isolated beating pig heart

    PubMed Central

    Otterspoor, Luuk C; van Nunen, Lokien X; Rosalina, Tilaï T; Veer, Marcel van’t; Tuijl, Sjoerd Van; Stijnen, Marco; Rutten, Marcel CM; van de Vosse, Frans N; Pijls, Nico HJ

    2017-01-01

    Hypothermia may attenuate reperfusion injury and thereby improve acute myocardial infarction therapy. Systemic cooling trials failed to reduce infarct size, perhaps because the target temperature was not reached fast enough. The use of selective intracoronary hypothermia combined with intracoronary temperature monitoring allows for titrating to target temperature and optimizing the cooling rate. We aimed to the test the feasibility of intracoronary cooling for controlled, selective myocardial hypothermia in an isolated beating pig heart. In five porcine hearts the left anterior descending artery (LAD) was occluded by an over-the-wire balloon (OTWB). After occlusion, saline at 22°C was infused through the OTWB lumen for 5 minutes into the infarct area at a rate of 30 ml/min. Thereafter the balloon was deflated but infusion continued with saline at 4°C for 5 minutes. Distal coronary temperature was continuously monitored by a pressure/temperature guidewire. Myocardial temperature at several locations in the infarct and control areas was recorded using needle thermistors. In the occlusion phase, coronary temperature decreased by 11.4°C (range 9.4-12.5°C). Myocardial temperature throughout the infarct area decreased by 5.1°C (range 1.8-8.1°C) within three minutes. During the reperfusion phase, coronary temperature decreased by 6.2°C (range 4.1-10.3°C) and myocardial temperature decreased by 4.5°C (range 1.5-7.4°C). Myocardial temperature outside the infarct area was not affected. In the isolated beating pig heart with acute occlusion of the LAD, we were able to rapidly “induce, maintain, and control” a stable intracoronary and myocardial target temperature of at least 4°C below body temperature without side effects and using standard PCI equipment, justifying further studies of this technique in humans. PMID:28337283

  16. Biphasic modulation of the mitochondrial electron transport chain in myocardial ischemia and reperfusion.

    PubMed

    Lee, Hsin-Ling; Chen, Chwen-Lih; Yeh, Steve T; Zweier, Jay L; Chen, Yeong-Renn

    2012-04-01

    Mitochondrial electron transport chain (ETC) is the major source of reactive oxygen species during myocardial ischemia-reperfusion (I/R) injury. Ischemic defect and reperfusion-induced injury to ETC are critical in the disease pathogenesis of postischemic heart. The properties of ETC were investigated in an isolated heart model of global I/R. Rat hearts were subjected to ischemia for 30 min followed by reperfusion for 1 h. Studies of mitochondrial function indicated a biphasic modulation of electron transfer activity (ETA) and ETC protein expression during I/R. Analysis of ETAs in the isolated mitochondria indicated that complexes I, II, III, and IV activities were diminished after 30 min of ischemia but increased upon restoration of flow. Immunoblotting analysis and ultrastructural analysis with transmission electron microscopy further revealed marked downregulation of ETC in the ischemic heart and then upregulation of ETC upon reperfusion. No significant difference in the mRNA expression level of ETC was detected between ischemic and postischemic hearts. However, reperfusion-induced ETC biosynthesis in myocardium can be inhibited by cycloheximide, indicating the involvement of translational control. Immunoblotting analysis of tissue homogenates revealed a similar profile in peroxisome proliferator-activated receptor-γ coactivator-1α expression, suggesting its essential role as an upstream regulator in controlling ETC biosynthesis during I/R. Significant impairment caused by ischemic and postischemic injury was observed in the complexes I- III. Analysis of NADH ferricyanide reductase activity indicated that injury of flavoprotein subcomplex accounts for 50% decline of intact complex I activity from ischemic heart. Taken together, our findings provide a new insight into the molecular mechanism of I/R-induced mitochondrial dysfunction.

  17. Cardioprotective effects of lixisenatide in rat myocardial ischemia-reperfusion injury studies

    PubMed Central

    2013-01-01

    Background Lixisenatide is a glucagon-like peptide-1 analog which stimulates insulin secretion and inhibits glucagon secretion and gastric emptying. We investigated cardioprotective effects of lixisenatide in rodent models reflecting the clinical situation. Methods The acute cardiac effects of lixisenatide were investigated in isolated rat hearts subjected to brief ischemia and reperfusion. Effects of chronic treatment with lixisenatide on cardiac function were assessed in a modified rat heart failure model after only transient coronary occlusion followed by long-term reperfusion. Freshly isolated cardiomyocytes were used to investigate cell-type specific mechanisms of lixisenatide action. Results In the acute setting of ischemia-reperfusion, lixisenatide reduced the infarct-size/area at risk by 36% ratio without changes on coronary flow, left-ventricular pressure and heart rate. Treatment with lixisenatide for 10 weeks, starting after cardiac ischemia and reperfusion, improved left ventricular end-diastolic pressure and relaxation time and prevented lung congestion in comparison to placebo. No anti-fibrotic effect was observed. Gene expression analysis revealed a change in remodeling genes comparable to the ACE inhibitor ramipril. In isolated cardiomyocytes lixisenatide reduced apoptosis and increased fractional shortening. Glucagon-like peptide-1 receptor (GLP1R) mRNA expression could not be detected in rat heart samples or isolated cardiomyocytes. Surprisingly, cardiomyocytes isolated from GLP-1 receptor knockout mice still responded to lixisenatide. Conclusions In rodent models, lixisenatide reduced in an acute setting infarct-size and improved cardiac function when administered long-term after ischemia-reperfusion injury. GLP-1 receptor independent mechanisms contribute to the described cardioprotective effect of lixisenatide. Based in part on these preclinical findings patients with cardiac dysfunction are currently being recruited for a randomized, double

  18. c-Jun DNAzymes inhibit myocardial inflammation, ROS generation, infarct size, and improve cardiac function after ischemia-reperfusion injury.

    PubMed

    Luo, Xiao; Cai, Hong; Ni, Jun; Bhindi, Ravinay; Lowe, Harry C; Chesterman, Colin N; Khachigian, Levon M

    2009-11-01

    Coronary reperfusion has been the mainstay therapy for reduced infarct size after a heart attack. However, this intervention also results in myocardial injury by initiating a marked inflammatory reaction, and new treatments are keenly sought. The basic-region leucine zipper protein, c-Jun is poorly expressed in the normal myocardium and is induced within 24 hours after myocardial ischemia-reperfusion injury. Synthetic catalytic DNA molecules (DNAzymes) targeting c-Jun (Dz13) reduce infarct size in the area-at-risk (AAR) regardless of whether it is delivered intramyocardially at the initiation of ischemia or at the time of reperfusion. Dz13 attenuates neutrophil infiltration, c-Jun and ICAM-1 expression in vascular endothelium, cardiomyocyte apoptosis, and the generation of reactive oxygen species in the reperfused myocardium. It inhibits infiltration into the AAR of complement 3 (C3), C3a receptor (C3aR), membrane attack complex-1 (Mac-1), or matrix metalloproteinase-2 (MMP-2) positive inflammatory cells. Dz13 also improves cardiac function without influencing myocardial vascularity or fibrosis. These findings demonstrate the regulatory role of c-Jun in the pathogenesis of myocardial inflammation and infarction following ischemia-reperfusion injury, and inhibition of this process using catalytic DNA.

  19. Red propolis ameliorates ischemic-reperfusion acute kidney injury.

    PubMed

    da Costa, Marcus Felipe Bezerra; Libório, Alexandre Braga; Teles, Flávio; Martins, Conceição da Silva; Soares, Pedro Marcos Gomes; Meneses, Gdayllon C; Rodrigues, Francisco Adelvane de Paulo; Leal, Luzia Kalyne Almeida Moreira; Miron, Diogo; Silva, Aline Holanda; Martins, Alice Maria Costa

    2015-08-15

    Acute kidney injury (AKI) remains a great problem in clinical practice. Renal ischemia/reperfusion (I/R) injury is a complex pathophysiological process. Propolis is a natural polyphenol-rich resinous substance collected by honeybees from a variety of plant sources that has anti-inflammatory and anti-oxidative properties. Red propolis (RP) protection in renal I/R injury was investigated. Male Wistar rats underwent unilateral nephrectomy and contralateral renal I/R (60 min). Rats were divided into four groups: (1) sham group, (2) RP group (sham-operated rats treated with RP), 3) IR group (rats submitted to ischemia) and (4) IR-RP (rats treated with RP before ischemia). At 48 h after reperfusion, renal function was assessed and kidneys were removed for analysis. I/R increased plasma levels of creatinine and reduced creatinine clearance (CrCl), and RP provided protection against this renal injury. Red propolis significantly improves oxidative stress parameters when compared with the IR group. Semiquantitative assessment of the histological lesions showed marked structural damage in I/R rats compared with the IR-RP rats. RP attenuates I/R-induced endothelial nitric oxide-synthase down regulation and increased heme-oxygenase expression in renal tissue. Red propolis protects kidney against acute ischemic renal failure and this protection is associated with reduced oxidative stress and eNOS and heme-oxygenase up regulation. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. [Analysis with the propensity score of the association between likelihood of treatment and event of interest in observational studies. An example with myocardial reperfusion].

    PubMed

    Martí, Helena; Pérez-Bárcena, Jon; Fiol, Miquel; Marrugat, Jaume; Navarro, Carmen; Aldasoro, Elena; Cabadés, Adolfo; Segura, Antonio; Masiá, Rafael; Turumbay, Javier; Cirera, Lluís; Arteagoitia, José M; Tomás, Carlos A; Vega, Gema; Sala, Joan; de Los Arcos, Enrique; Tormo, María J; Hurtado-de-Saracho, Iraida; Francés-Sempere, Mercedes; Elosua, Roberto

    2005-02-01

    Analysis of the effect of treatment in observational studies is complex due to differences between treated and nontreated patients. Calculating the probability of receiving treatment conditioned on relevant covariates (propensity score [PS]) has been proposed as a method to control for these differences. We report an application of PS to assess the association between reperfusion treatment and 28-day case fatality in patients with acute myocardial infarction (AMI). We describe the procedure used to calculate PS for receiving reperfusion treatment, and different strategies to analyze the association between PS and case fatality with regression modeling and matching. Data were from a population-based registry of 6307 patients with AMI in Spain during 1997-98. The PS for reperfusion was calculated in 5622 patients. In the multivariate analysis, reperfusion was associated with lower case fatality (OR = 0.59; 95% confidence interval [95% CI]: 0.46-0.77). When PS was included as a covariate, this association became non- significant (OR = 0.76; 95% CI: 0.57-1.01). In the subgroup of matched patients with a similar PS (n = 3138), treatment was not associated with case fatality (OR = 0.95; 95% CI: 0.72-1.26). When the influence of cases with missing data on PS was controlled for, reperfusion treatment was associated with lower fatality (OR = 0.66; 95% CI: 0.55-0.80). Calculating propensity score is a method that controls for differences between treated and nontreated patients. This score has limitations when matching is incomplete and when data are missing. Results of the present example suggest that reperfusion treatment reduces AMI case fatality.

  1. Aldehyde Dehydrogenase 2 Has Cardioprotective Effects on Myocardial Ischaemia/Reperfusion Injury via Suppressing Mitophagy

    PubMed Central

    Ji, Wenqing; Wei, Shujian; Hao, Panpan; Xing, Junhui; Yuan, Qiuhuan; Wang, Jiali; Xu, Feng; Chen, Yuguo

    2016-01-01

    Mitophagy, a selective form of autophagy, is excessively activated in myocardial ischemia/reperfusion (I/R). The study investigated whether aldehyde dehydrogenase 2 (ALDH2) exerted its cardioprotective effect by regulating mitophagy. Myocardial infarct size and apoptosis after I/R in rats were ameliorated by Alda-1, an ALDH2 activator, and aggravated by ALDH2 inhibition. Both in I/R rats and hypoxia/reoxygenation H9C2 cells, ALDH2 activation suppressed phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/Parkin expression, regulating mitophagy, by preventing 4-hydroxynonenal, reactive oxygen species and mitochondrial superoxide accumulation. Furthermore, the effect was enhanced by ALDH2 inhibition. Thus, ALDH2 may protect hearts against I/R injury by suppressing PINK1/Parkin–dependent mitophagy. PMID:27148058

  2. The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited

    PubMed Central

    Kurian, Gino A.; Rajagopal, Rashmi; Vedantham, Srinivasan; Rajesh, Mohanraj

    2016-01-01

    Oxidative and reductive stress are dual dynamic phases experienced by the cells undergoing adaptation towards endogenous or exogenous noxious stimulus. The former arises due to the imbalance between the reactive oxygen species production and antioxidant defenses, while the latter is due to the aberrant increase in the reducing equivalents. Mitochondrial malfunction is the common denominator arising from the aberrant functioning of the rheostat that maintains the homeostasis between oxidative and reductive stress. Recent experimental evidences suggest that the maladaptation during oxidative stress could play a pivotal role in the pathophysiology of major cardiovascular diseases such as myocardial infraction, atherosclerosis, and diabetic cardiovascular complications. In this review we have discussed the role of oxidative and reductive stress pathways in the pathogenesis of myocardial ischemia/reperfusion injury and diabetic cardiomyopathy (DCM). Furthermore, we have provided impetus for the development of subcellular organelle targeted antioxidant drug therapy for thwarting the deterioration of the failing myocardium in the aforementioned cardiovascular conditions. PMID:27313825

  3. Ginkgolide B Reduces the Degradation of Membrane Phospholipids to Prevent Ischemia/Reperfusion Myocardial Injury in Rats.

    PubMed

    Pei, Hong-Xia; Hua, Rong; Guan, Cha-Xiang; Fang, Xiang

    2015-01-01

    Platelet-activating factor (PAF), a bioactive phospholipid, plays an important role in the integrity of the cellular membrane structure, and is involved in the pathogenesis of myocardial ischemia/reperfusion (IR) injuries. In this study, we tested the hypothesis that blockage of PAF receptor by BN 52021 (Ginkgolide B) can prevent IR-induced degradation of the myocardial membrane phospholipid, and deterioration of the cardiac function. Rat hearts in situ were subjected to 5 min ischemia and followed by 10 min reperfusion. Cardiac performances during periods of ischemia and reperfusion were monitored, and the amount of membrane phospholipids was analyzed. Myocardial total phospholipids, phosphatidylcholine, and phosphatidylethanolamine were decreased significantly in ischemia-reperfusion rat hearts compared with those of sham-operated rat hearts. Degradation of the membrane phospholipid was accompanied by the deterioration of cardiac functions and increase in serum lactate dehydrogenase (LDH) activity. BN 52021 (15 mg/kg), given by intravenous infusion 10 min prior to the left anterior descending coronary artery occlusion, reduced IR-related degradation of the myocardial phospholipids, the activity of serum LDH, and was concomitant with improvement of cardiac function. Furthermore, we demonstrated that the production of PAF was increased and BN 52021 decreased cellular damage in cultured anoxic cardiomyocytes. These results indicated that PAF antagonist BN 52021 has a protective effect against IR-induced myocardial dysfunction and degradation of the membrane phospholipids. © 2015 S. Karger AG, Basel.

  4. The effect of reperfusion and hyperemia on the biodistribution of the myocardial imaging agent, Tc-99m TBI

    SciTech Connect

    Holman, B.L.; Campbell, C.I.; Lister-James, J.; Jones, A.G.; Kloner, R.A.

    1985-05-01

    The behavior of Tc-99m t-butylisonitrile (TBI) was studied in the dog at rest and under conditions of hyperemia and reperfusion. After permanent occlusion of the left anterior descending artery (LAD), the correlation between the relative myocardial concentration of Tc-99m TBI and regional myocardial blood flow (MBF) was excellent (y=0.97x-1.03 (r=0.98)). In a dog model of transient hyperemia, Tc-99m TBI underestimated MBF (53 +- 10% at 3.0 +- 0.2 times normal flow and 41 +- 10% at 6.1 +- 4 times normal flow). When Tc-99m TBI was injected 3 min before reperfusion of the LAD in dogs sacrificed 10, 30 and 60 min after reperfusion, TBI and T1-201 concentrations (as a percentage of concentration in normal tissue) were 75% and 65% at 10 min after reperfusion; 79% and 73% at 30 min; and 38% and 31% at 60 min in regions where flow was reduced to 38%, 15% and 10% of normal MBF prior to reperfusion. There was no significant reduction in the rate of reperfusion when Tc-99m TBI was injected 10 min prior to reperfusion. When TBI was injected directly into the canine LAD, washout was slow (86% of maximum at 50 min and 79% at 120 min after injection. The authors conclude that Tc-99m TBI reflects regional MBF accurately in ischemic and normal resting myocardium and underestimates MBF at high values. The rate of myocardial redistribution for Tc-99m TBI after reperfusion in the animal model is similar to that for T1-201.

  5. Registry of "early latecomer" patients with acute ST-segment elevation myocardial infarction at the Instituto Nacional Cardiovascular INCOR - Peru.

    PubMed

    Chacón-Diaz, Manuel Alberto; Barrios-Escalante, Jorge Alonso; Espinoza-Alva, Daniel

    2016-01-01

    To assess the features of asymptomatic patients with acute ST segment elevation myocardial infarction who presents to the emergency with more than 12h of evolution, and if there is a benefit of an invasive versus medical therapy. Retrospective, cohort study from January 2012 to December 2014, we compare the outcomes at 6 and 12 months of follow up of the invasive group versus the conservative group. There were no differences in outcomes at 12 months between an invasive versus a conventional strategy; but, looking at the reperfusion state, we found more risk of death and heart failure at 12 months in the no-reperfused group versus the reperfused group (40% versus 0%, OR: 2, CI: 1.2-3.1, p=0.028 for mortality and 53% versus 0%, OR: 2.2, CI: 1.3-3.98, p=0.007 for heart failure). In patients with ST elevation acute myocardial infarction with more than 12h of evolution, the invasive strategy with optimal reperfusion is better than the conservative management or no reperfusion in terms of less mortality and heart failure at 12 months of follow up. Copyright © 2015 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  6. [Acute myocardial infarction in the elderly. The FAST-MI registry].

    PubMed

    Puymirat, Etienne; Aissaoui, Nadia; Simon, Tabassome; Bataille, Vincent; Drouet, Elodie; Mulak, Geneviève; Ferrières, Jean; Danchin, Nicolas

    2013-11-01

    The FAST-MI 2010 registry collected information on characteristics and management of patients hospitalized for acute myocardial infraction during a one-month period in 213 centers across France, at the end of 2010. Among the 3079 patients included, 31% were aged 75 years or over (25% of those with ST-elevation myocardial infarction, and 38% of those with non-ST-elevation myocardial infarction). The clinical profile and risk factors differ in elderly patients, but chest pain remains the most common presenting symptom, although a substantial percentage of patients also present with signs of heart failure. Elderly individuals receive less recommended medications, including reperfusion therapy for STEMI, with the largest difference observed beyond 85 years of age. In-hospital mortality increases with age, particularly after 85 years, but has decreased compared with previous French surveys. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Clinic Predictive Factors for Insufficient Myocardial Reperfusion in ST-Segment Elevation Myocardial Infarction Patients Treated with Selective Aspiration Thrombectomy during Primary Percutaneous Coronary Intervention.

    PubMed

    Tian, Jinfan; Liu, Yue; Song, Xiantao; Zhang, Min; Xu, Feng; Yuan, Fei; Lyu, Shuzheng

    2016-01-01

    Background. Insufficient data are available on the potential benefit of selective aspiration and clinical predictors for no-reflow in STEMI patients undergoing primary percutaneous coronary intervention (PPCI) adjunct with aspiration thrombectomy. Objective. The aim of our study was to investigate clinical predictors for insufficient reperfusion in patients with high thrombus burden treated with PPCI and manual aspiration thrombectomy. Methods. From January 2011 till December 2015, 277 STEMI patients undergoing manual aspiration thrombectomy and PPCI were selected and 202 patients with a Thrombolysis in Myocardial Infarction (TIMI) thrombus grade 4~5 were eventually involved in our study. According to a cTFC value, patients were divided into Group I (cTFC > 40), namely, insufficient reperfusion group; Group II (cTFC ≤ 40), namely, sufficient reperfusion group. Results. Univariate analysis showed that hypertension, multivessel disease, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were negative predictors for insufficient reperfusion. After multivariate adjustment, age ≧ 60 years, hypertension, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were independently associated with insufficient reperfusion in STEMI patients treated with manual aspiration thrombectomy. Upfront intracoronary GP IIb/IIIa inhibitor (Tirofiban) was positively associated with improved myocardial reperfusion. Conclusion. Fully identifying risk factors will help to improve the effectiveness of selective thrombus aspiration.

  8. Clinic Predictive Factors for Insufficient Myocardial Reperfusion in ST-Segment Elevation Myocardial Infarction Patients Treated with Selective Aspiration Thrombectomy during Primary Percutaneous Coronary Intervention

    PubMed Central

    Song, Xiantao; Zhang, Min; Xu, Feng; Yuan, Fei

    2016-01-01

    Background. Insufficient data are available on the potential benefit of selective aspiration and clinical predictors for no-reflow in STEMI patients undergoing primary percutaneous coronary intervention (PPCI) adjunct with aspiration thrombectomy. Objective. The aim of our study was to investigate clinical predictors for insufficient reperfusion in patients with high thrombus burden treated with PPCI and manual aspiration thrombectomy. Methods. From January 2011 till December 2015, 277 STEMI patients undergoing manual aspiration thrombectomy and PPCI were selected and 202 patients with a Thrombolysis in Myocardial Infarction (TIMI) thrombus grade 4~5 were eventually involved in our study. According to a cTFC value, patients were divided into Group I (cTFC > 40), namely, insufficient reperfusion group; Group II (cTFC ≤ 40), namely, sufficient reperfusion group. Results. Univariate analysis showed that hypertension, multivessel disease, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were negative predictors for insufficient reperfusion. After multivariate adjustment, age ≧ 60 years, hypertension, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were independently associated with insufficient reperfusion in STEMI patients treated with manual aspiration thrombectomy. Upfront intracoronary GP IIb/IIIa inhibitor (Tirofiban) was positively associated with improved myocardial reperfusion. Conclusion. Fully identifying risk factors will help to improve the effectiveness of selective thrombus aspiration. PMID:27891513

  9. Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction

    PubMed Central

    Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Éric; Gaudreault, Valérie

    2014-01-01

    A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause. PMID:25276306

  10. Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction.

    PubMed

    Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Eric; Gaudreault, Valérie

    2014-09-26

    A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause.

  11. Anti-apoptotic effect of benidipine, a long-lasting vasodilating calcium antagonist, in ischaemic/reperfused myocardial cells.

    PubMed

    Gao, F; Gong, B; Christopher, T A; Lopez, B L; Karasawa, A; Ma, X L

    2001-02-01

    1. Ischaemia/reperfusion causes intracellular calcium overloading in cardiac cells. Administration of calcium antagonists reduces myocardial infarct size. Recent in vitro studies have demonstrated that calcium plays a critical role in the signal transduction pathway leading to apoptosis. However, whether or not calcium antagonists may reduce myocardial apoptosis induced by ischaemia-reperfusion, and thus decrease myocardial infarction, has not been directly investigated. 2. The present study investigated the effects of benidipine, an L-type calcium channel blocker, on myocardial infarct size, apoptosis, necrosis and cardiac functional recovery in rabbits subjected to myocardial ischaemia/reperfusion (MI/R, 45 min/240 min). Ten minutes prior to coronary occlusion, rabbits were treated with vehicle or benidipine (10 microg x kg(-1) or 3 microg x kg(-1), i.v.). 3. In the vehicle-treated group, MI/R caused cardiomyocyte apoptosis as evidenced by DNA ladder formation and TUNEL positive nuclear staining (12.2+/-1.1%). Treatment with 10 microg x kg(-1) benidipine lowered blood pressure, decreased myocardial apoptosis (6.2+/-0.8%, P<0.01 vs vehicle) and necrosis, reduced infarct size (20+/-2.3% vs 49+/-2.6%, P<0.01), and improved cardiac functional recovery after reperfusion. Administering benidipine at 3 microg x kg(-1), a dose at which no haemodynamic effect was observed, also exerted significant anti-apoptosis effects, which were not significantly different from those observed with higher dose benidipine treatment. However, treatment with this low dose benidipine failed to reduce myocardial necrosis. 4. These results demonstrate that benidipine, a calcium antagonist, exerts significant anti-apoptosis effects, which are independent of haemodynamic changes. Administration of benidipine at a higher dose produced favourable haemodynamic effects and provided additional protection against myocardial necrotic injury and further improved cardiac functional recovery.

  12. Pramipexole pretreatment attenuates myocardial ischemia/reperfusion injury through upregulation of autophagy.

    PubMed

    Mo, Yingli; Tang, Lu; Ma, Yi; Wu, Saizhu

    2016-05-13

    This article investigated the effects of pramipexole on myocardial ischemia reperfusion (I/R) injury and its underlying mechanisms. We utilized an in vivo mouse model of myocardial I/R injury and an in vitro H9c2 cell model of hypoxia/reoxygenation (H/R) injury. Pramipexole pretreatment in male C57BL/6 mice significantly reduced the myocardial infarction size, decreased the CK and LDH activities at the serum level and enhanced autophagy. In the in vitro study, the pramipexole treatment significantly elevated the survival rate, decreased the LDH activity, reduced ROS generation and restored the ΔΨm in H9C2 cells during H/R. Additionally, its use could increase the autophagy flux level in H9c2 cells. The underlying mechanisms were determined by measuring the expression of the autophagic protein levels. These results further indicated that pramipexole treatment modulated H/R-induced autophagy via an AMPK-dependent pathway. All of these data indicate that pramipexole exerted protective effects against myocardial I/R injury and enhanced autophagy in part through the AMPK-mediated pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Apelin/APJ System: A Novel Therapeutic Target for Myocardial Ischemia/Reperfusion Injury.

    PubMed

    Chen, Zhe; Wu, Di; Li, Lanfang; Chen, Linxi

    2016-12-01

    Apelin is the endogenous ligand of the G protein-coupled receptor, APJ. Recently, researches indicate that the apelin/APJ system involves in myocardial ischemia-reperfusion injury (MIRI), which is a common pathophysiological process in patients with heart diseases and therapies. The reperfusion induces the expression of apelin and APJ receptor, which play an important role in cardioprotection of MIRI. The apelin/APJ system alleviates MIRI mainly by decreasing mitochondrial reactive oxygen species and delaying the opening of mitochondrial permeability transition pores, which induce the initiation of mitophagy. Besides, the apelin/APJ system prevents mitochondrial oxygen damage and lipid peroxidation through nitric oxide formation. The apelin/APJ system also improves MIRI through other pathways, including promoting metabolic and functional recovery, significantly increasing myocardial capillary density and arteriole formation, inhibiting endoplasmic reticulum stress-induced cell apoptosis, and maintaining integrity of cell membranes. In this review, we discuss how the mechanisms of the apelin/APJ system reverse MIRI in detail and elaborate on APJ agonists, which may be used for therapy of MIRI.

  14. The PPAR-α activator fenofibrate fails to provide myocardial protection in ischemia and reperfusion in pigs

    PubMed Central

    Xu, Ya; Lu, Li; Greyson, Clifford; Rizeq, Mona; Nunley, Karin; Wyatt, Beata; Bristow, Michael R.; Long, Carlin S.; Schwartz, Gregory G.

    2010-01-01

    Rodent studies suggest that peroxisome proliferator-activated receptor-α (PPAR-α) activation reduces myocardial ischemia-reperfusion (I/R) injury and infarct size; however, effects of PPAR-α activation in large animal models of myocardial I/R are unknown. We determined whether chronic treatment with the PPAR-α activator fenofibrate affects myocardial I/R injury in pigs. Domestic farm pigs were assigned to treatment with fenofibrate 50 mg·kg−1 ·day−1 orally or no drug treatment, and either a low-fat (4% by weight) or a high-fat (20% by weight) diet. After 4 wk, 66 pigs underwent 90 min low-flow regional myocardial ischemia and 120 min reperfusion under anesthetized open-chest conditions, resulting in myocardial stunning. The high-fat group received an infusion of triglyceride emulsion and heparin during this terminal experiment to maintain elevated arterial free fatty acid (FFA) levels. An additional 21 pigs underwent 60 min no-flow ischemia and 180 min reperfusion, resulting in myocardial infarction. Plasma concentration of fenofibric acid was similar to the EC50 for activation of PPAR-α in vitro and to maximal concentrations achieved in clinical use. Myocardial expression of PPAR-α mRNA was prominent but unaffected by fenofibrate treatment. Fenofibrate increased expression of carnitine palmitoyltransferase (CPT)-I mRNA in liver and decreased arterial FFA and lactate concentrations (each P < 0.01). However, fenofibrate did not affect myocardial CPT-I expression, substrate uptake, lipid accumulation, or contractile function during low-flow I/R in either the low- or high-fat group, nor did it affect myocardial infarct size. Despite expression of PPAR-α in porcine myocardium and effects of fenofibrate on systemic metabolism, treatment with this PPAR-α activator does not alter myocardial metabolic or contractile responses to I/R in pigs. PMID:16339839

  15. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

    PubMed Central

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

    2016-01-01

    Kaempferol (KMP), a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR) model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p.) was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB), inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3), TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2). In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway. PMID:27087891

  16. Niacin-bound chromium enhances myocardial protection from ischemia-reperfusion injury.

    PubMed

    Thirunavukkarasu, Mahesh; Penumathsa, Suresh Varma; Juhasz, Bela; Zhan, Lijun; Cordis, Gerald; Altaf, Elham; Bagchi, Manashi; Bagchi, Debasis; Maulik, Nilanjana

    2006-08-01

    A novel niacin-bound, chromium-based energy formula (EF; InterHealth Nutraceuticals, Benicia, CA) has been developed in conjunction with D-ribose, caffeine, ashwagandha extract (containing 5% withanolides), and selected amino acids. We have assessed the efficacy of oral administration of EF (40 mg x kg body wt(-1) x day(-1)) in male and female rats over a period of 90 consecutive days on the cardiovascular and pathophysiological functions in an isolated rat heart model. After 30, 60, and 90 days of treatment with EF, the hearts of male and female rats were subjected to 30 min of global ischemia followed by 2 h of reperfusion and were measured for myocardial ATP, creatine phosphate (CP), phosphorylated AMP kinase (p-AMPK), and heat shock proteins. Myocardial ATP and CP levels were increased in both male and female rats after EF treatment compared with the controls. Western blot analyses were performed to quantify the expression of stress-related proteins such as heat shock proteins (HSP-70, -32, and -25) and are found to be increased in both male and female rats after EF treatment. The p-AMPK level, which is a sensor for the energy state in various cell types, was also found to be increased after treatment with EF in both male and female rats. Aortic flow, maximum first derivative of developed pressure, left ventricular developed pressure, and infarct size were observed after ischemia-reperfusion and found to be significantly improved in EF-treated rats compared with control animals. Thus EF demonstrated long-term safety as well as exhibiting significant cardioprotective ability during ischemia and reperfusion injury by increased energy production, improved cardiac function, and reduced infarct size.

  17. Cardioprotection by a novel recombinant serine protease inhibitor in myocardial ischemia and reperfusion injury.

    PubMed

    Murohara, T; Guo, J P; Lefer, A M

    1995-09-01

    Polymorphonuclear neutrophils (PMN) play an important role in myocardial ischemia/reperfusion (MI/R) injury; however, the role of neutrophilic proteases is less understood. The effects of a novel serine protease inhibitor (serpin), LEX032, were investigated in a murine model of MI (20 min) and R (24 hr) injury in vivo. LEX032 is a recombinant human alpha 1-antichymotrypsin in which six amino acid residues were replaced around the active center with those of alpha-1 protease inhibitor. LEX032 has the ability to inhibit both neutrophil elastase and cathepsin G, two major neutral serine proteases in neutrophils, as well as superoxide generation. LEX032 (25 or 50 mg/kg) administered i.v. 1 min before reperfusion significantly attenuated myocardial necrotic injury evaluated by cardiac creatine kinase loss compared to MI/R rats receiving only vehicle (P < .001). Moreover, cardiac myeloperoxidase activity, an index of PMN accumulation, in the ischemic myocardium was significantly attenuated by LEX032 as compared with rats receiving vehicle (P < .001). LEX032 also moderately attenuated leukotriene B4-stimulated PMN adherence to rat superior mesenteric artery endothelium and markedly diminished superoxide radical release from LTB4-stimulated PMN in vitro. In a glycogen-induced rat peritonitis model, LEX032 (50 mg/kg) significantly attenuated PMN transmigration into the peritoneal cavity in vivo. In conclusion, the recombinant serine protease inhibitor, LEX032, appears to be an effective agent for attenuating MI/R injury by inhibiting neutrophil-accumulation into the ischemic-reperfused myocardium and by inactivating cytotoxic metabolites (proteases and superoxide radical) released from neutrophils.

  18. Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury.

    PubMed

    Liu, Baoshan; Wang, Jiali; Li, Minghua; Yuan, Qiuhuan; Xue, Mengyang; Xu, Feng; Chen, Yuguo

    2016-12-27

    Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). ALDH2 O-GlcNAc modification was increased whereas its activity was decreased in AHG+I/R and DM+I/R rats. High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). Accordingly, ALDH2 activity was decreased by 18.1% in Con+PUGNAc group whereas it was increased by 17.9% in Con+DON group. Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection.

  19. How reliable is myocardial imaging in the diagnosis of acute myocardial infarction

    SciTech Connect

    Willerson, J.T.

    1983-01-01

    Myocardial scintigraphic techniques available presently allow a sensitive and relatively specific diagnosis of acute myocardial infarction when they are used correctly, although every technique has definite limitations. Small myocardial infarcts (less than 3 gm.) may be missed, and there are temporal limitations in the usefulness of the scintigraphic techniques. The development of tomographic methodology that may be used with single-photon radionuclide emitters (including technetium and /sup 201/Tl will allow the detection of relatively small abnormalities in myocardial perfusion and regions of myocardial infarction and will help to provide a more objective interpretation of the myocardial scintigrams. The use of overlay techniques allowing simultaneous assessment of myocardial perfusion, infarct-avid imaging, and radionuclide ventriculograms will provide insight into the relevant aspects of the extent of myocardial damage, the relationship of damage to myocardial perfusion, and the functional impact of myocardial infarction on ventricular performance.

  20. Amphetamine Abuse Related Acute Myocardial Infarction.

    PubMed

    Sinha, Archana; Lewis, O'Dene; Kumar, Rajan; Yeruva, Sri Lakshmi Hyndavi; Curry, Bryan H

    2016-01-01

    Amphetamine abuse is a global problem. The cardiotoxic manifestations like acute myocardial infarction (AMI), heart failure, or arrhythmia related to misuse of amphetamine and its synthetic derivatives have been documented but are rather rare. Amphetamine-related AMI is even rarer. We report two cases of men who came to emergency department (ED) with chest pain, palpitation, or seizure and were subsequently found to have myocardial infarction associated with the use of amphetamines. It is crucial that, with increase in amphetamine abuse, clinicians are aware of this potentially dire complication. Patients with low to intermediate risk for coronary artery disease with atypical presentation may benefit from obtaining detailed substance abuse history and urine drug screen if deemed necessary.

  1. Myocardial Edema Imaging in Acute Coronary Syndromes

    PubMed Central

    Walls, Michael C.; Verhaert, David; Raman, Subha V.

    2011-01-01

    Acute coronary syndromes (ACS) continue to be the most common morbid condition of industrialized nations. The advent of and technical improvements in revascularization and medical therapy have led to a steady decline in mortality rates. However, many patients who suffer unstable angina or myocardial infarction require further testing and risk stratification to guide therapeutic selection and prognosis assignment. Myocardial edema imaging with cardiac magnetic resonance (CMR) affords the ability to define the amount of myocardium at risk, refine estimates of prognosis and provide guidance for therapies with excellent sensitivity compared to standard clinical markers. This review will discuss the rationale for edema imaging, how it is performed using CMR and its potential clinical applications. PMID:22102557

  2. Painless acute myocardial infarction on Mount Kilimanjaro.

    PubMed

    Jamal, Nasiruddin; Rajhy, Mubina; Bapumia, Mustaafa

    2016-03-17

    An individual experiencing dyspnoea or syncope at high altitude is commonly diagnosed to have high-altitude pulmonary edema or cerebral edema. Acute myocardial infarction (AMI) is generally not considered in the differential diagnosis. There have been very rare cases of AMI reported only from Mount Everest. We report a case of painless ST segment elevation myocardial infarction (STEMI) that occurred while climbing Mount Kilimanjaro. A 51-year-old man suffered dyspnoea and loss of consciousness near the mountain peak, at about 5600 m. At a nearby hospital, he was treated as a case of high-altitude pulmonary edema. ECG was not obtained. Two days after the incident, he presented to our institution with continued symptoms of dyspnoea, light-headedness and weakness, but no pain. He was found to have inferior wall and right ventricular STEMI complicated by complete heart block. He was successfully managed with coronary angioplasty, with good recovery. 2016 BMJ Publishing Group Ltd.

  3. Amphetamine Abuse Related Acute Myocardial Infarction

    PubMed Central

    Lewis, O'Dene; Kumar, Rajan; Yeruva, Sri Lakshmi Hyndavi; Curry, Bryan H.

    2016-01-01

    Amphetamine abuse is a global problem. The cardiotoxic manifestations like acute myocardial infarction (AMI), heart failure, or arrhythmia related to misuse of amphetamine and its synthetic derivatives have been documented but are rather rare. Amphetamine-related AMI is even rarer. We report two cases of men who came to emergency department (ED) with chest pain, palpitation, or seizure and were subsequently found to have myocardial infarction associated with the use of amphetamines. It is crucial that, with increase in amphetamine abuse, clinicians are aware of this potentially dire complication. Patients with low to intermediate risk for coronary artery disease with atypical presentation may benefit from obtaining detailed substance abuse history and urine drug screen if deemed necessary. PMID:26998366

  4. Cardioprotective Effects of Salvianolic Acid A on Myocardial Ischemia-Reperfusion Injury In Vivo and In Vitro

    PubMed Central

    Fan, Huaying; Yang, Liu; Fu, Fenghua; Xu, Hui; Meng, Qinggang; Zhu, Haibo; Teng, Lirong; Yang, Mingyan; Zhang, Leiming; Zhang, Ziliang; Liu, Ke

    2012-01-01

    Salvianolic acid A (SAA), one of the major active components of Danshen that is a traditional Chinese medicine, has been reported to possess protective effect in cardiac diseases and antioxidative activity. This study aims to investigate the cardioprotection of SAA in vivo and in vitro using the model of myocardial ischemia-reperfusion in rat and hydrogen peroxide (H2O2)-induced H9c2 rat cardiomyoblasts apoptosis. It was found that SAA significantly limited infarct size of ischemic myocardium when given immediately prior to reperfusion. SAA also significantly suppressed cellular injury and apoptotic cell death. Additionally, the results of western blot and phospho-specific antibody microarray analysis showed that SAA could up-regulate Bcl-2 expression and increase the phosphorylation of proteins such as Akt, p42/p44 extracellular signal-related kinases (Erk1/2), and their related effectors. The phosphorylation of those points was related to suppress apoptosis. In summary, SAA possesses marked protective effect on myocardial ischemia-reperfusion injury, which is related to its ability to reduce myocardial cell apoptosis and damage induced by oxidative stress. The protection is achieved via up-regulation of Bcl-2 expression and affecting protein phosphorylation. These findings indicate that SAA may be of value in cardioprotection during myocardial ischemia-reperfusion injury, which provide pharmacological evidence for clinical application. PMID:21789047

  5. Primary coronary angioplasty for acute myocardial infarction (the Primary Angioplasty Registry).

    PubMed

    O'Neill, W W; Brodie, B R; Ivanhoe, R; Knopf, W; Taylor, G; O'Keefe, J; Grines, C L; Weintraub, R; Sickinger, B G; Berdan, L G

    1994-04-01

    During a 14-month period, 6 experienced centers prospectively enrolled 271 patients into a registry in which percutaneous transluminal coronary angioplasty was the primary treatment for acute myocardial infarction. Patients age > 18 years who presented with ST-segment elevation on the 12-lead electrocardiogram were enrolled if symptom duration was < 12 hours and there was no proclivity for bleeding. An independent core angiographic laboratory processed the angiographic data. Of 271 patients giving informed consent, 245 (90%) were deemed anatomically suitable and underwent angioplasty therapy. Upon leaving the catheterization laboratory 98% of patients had achieved reperfusion; 92% had a residual visual stenosis < or = 50%. Emergency bypass surgery was required in 14 patients (5%) for either failed angioplasty (n = 3) or presumed life-threatening anatomy (n = 11). The in-hospital mortality rate was 4%, whereas the reinfarction rate was 3% and the stroke rate was 1%, with 1 intracranial hemorrhage and 2 embolic events. Bleeding requiring > or = 2 units of blood occurred in 46 patients (18%); 14 of these transfusions were related to coronary artery bypass surgery. Primary angioplasty is associated with a high reperfusion rate, low in-hospital mortality and few recurrent myocardial ischemic events. These results point to the need for a large-scale trial comparing angioplasty with thrombolytic therapy in the setting of acute myocardial infarction.

  6. A practical approach to remote ischemic preconditioning and ischemic preconditioning against myocardial ischemia/reperfusion injury

    PubMed Central

    Totzeck, Matthias; Hendgen-Cotta, Ulrike B.; French, Brent A.; Rassaf, Tienush

    2016-01-01

    Although urgently needed in clinical practice, a cardioprotective therapeutic approach against myocardial ischemia/ reperfusion injury remains to be established. Remote ischemic preconditioning (rIPC) and ischemic preconditioning (IPC) represent promising tools comprising three entities: the generation of a protective signal, the transfer of the signal to the target organ, and the response to the transferred signal resulting in cardioprotection. However, in light of recent scientific advances, many controversies arise regarding the efficacy of the underlying signaling. We here show methods for the generation of the signaling cascade by rIPC as well as IPC in a mouse model for in vivo myocardial ischemia/ reperfusion injury using highly reproducible approaches. This is accomplished by taking advantage of easily applicable preconditioning strategies compatible with the clinical setting. We describe methods for using laser Doppler perfusion imaging to monitor the cessation and recovery of perfusion in real time. The effects of preconditioning on cardiac function can also be assessed using ultrasound or magnetic resonance imaging approaches. On a cellular level, we confirm how tissue injury can be monitored using histological assessment of infarct size in conjunction with immunohistochemistry to assess both aspects in a single specimen. Finally, we outline, how the rIPC-associated signaling can be transferred to the target cell via conservation of the signal in the humoral (blood) compartment. This compilation of experimental protocols including a conditioning regimen comparable to the clinical setting should proof useful to both beginners and experts in the field of myocardial infarction, supplying information for the detailed procedures as well as troubleshooting guides. PMID:28066791

  7. Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema.

    PubMed

    Desai, Ketaki V; Laine, Glen A; Stewart, Randolph H; Cox, Charles S; Quick, Christopher M; Allen, Steven J; Fischer, Uwe M

    2008-06-01

    Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures.

  8. Acute Anterior Myocardial Infarction Accompanied by Acute Inferior Myocardial Infarction: A Very Rare Coronary Artery Anomaly.

    PubMed

    Alsancak, Y; Sezenöz, B; Duran, M; Unlu, S; Turkoglu, S; Yalcın, R

    2015-01-01

    Coronary artery anomalies are rare and mostly silent in clinical practice. First manifestation of this congenital abnormality can be devastating as syncope, acute coronary syndrome, and sudden cardiac death. Herein we report a case with coronary artery anomaly complicated with ST segment myocardial infarction in both inferior and anterior walls simultaneously diagnosed during primary percutaneous coronary intervention.

  9. The impact of ischemia-reperfusion injury on the effectiveness of primary angioplasty in ST-segment elevation myocardial infarction

    PubMed Central

    Grygier, Marek; Lesiak, Maciej; Grajek, Stefan

    2013-01-01

    The most effective method of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (PCI), assisted by aspiration thrombectomy and administration of antiplatelet agents and anticoagulants. However, effective restoration of blood flow in the infarct-related artery may paradoxically result in further damage to the heart muscle. This phenomenon, called ischemia-reperfusion injury (IRI), can significantly reduce the beneficial effects of reperfusion therapy. The rapid restoration of blood flow to the previously ischemic area causes a number of pathophysiological mechanisms leading to increased necrosis of myocytes still viable at the end of the ischemic period. It has been postulated that there are several strategies that can reduce damage to the heart muscle. Attempts to translate the results of experimental trials has been disappointing. More recently, however, some of the clinical benefits of ischemic postconditioning in which reperfusion in patients with STEMI who are undergoing PCI is interrupted with short episodes of ischemia were demonstrated. This renewed the interest in the reperfusion phase as a target for cardioprotective therapy. Research in this field has also been reinforced by the discovery of new potential targets for treatment that protects against IRI, such as the kinase pathway to protect against damage (reperfusion injury salvage kinases – RISK) and mitochondrial permeability transition pore. It seems that these findings will help to develop strategies that will improve the efficiency of mechanical reperfusion and may translate into long-term clinical effects. PMID:24570732

  10. Temporal Evolution of Myocardial Hemorrhage and Edema in Patients After Acute ST-Segment Elevation Myocardial Infarction: Pathophysiological Insights and Clinical Implications.

    PubMed

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

    2016-02-23

    The time course and relationships of myocardial hemorrhage and edema in patients after acute ST-segment elevation myocardial infarction (STEMI) are uncertain. Patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention underwent cardiac magnetic resonance imaging on 4 occasions: at 4 to 12 hours, 3 days, 10 days, and 7 months after reperfusion. Myocardial edema (native T2) and hemorrhage (T2*) were measured in regions of interest in remote and injured myocardium. Myocardial hemorrhage was taken to represent a hypointense infarct core with a T2* value <20 ms. Thirty patients with ST-segment elevation myocardial infarction (mean age 54 years; 25 [83%] male) gave informed consent. Myocardial hemorrhage occurred in 7 (23%), 13 (43%), 11 (33%), and 4 (13%) patients at 4 to 12 hours, 3 days, 10 days, and 7 months, respectively, consistent with a unimodal pattern. The corresponding median amounts of myocardial hemorrhage (percentage of left ventricular mass) during the first 10 days after myocardial infarction were 2.7% (interquartile range [IQR] 0.0-5.6%), 7.0% (IQR 4.9-7.5%), and 4.1% (IQR 2.6-5.5%; P<0.001). Similar unimodal temporal patterns were observed for myocardial edema (percentage of left ventricular mass) in all patients (P=0.001) and for infarct zone edema (T2, in ms: 62.1 [SD 2.9], 64.4 [SD 4.9], 65.9 [SD 5.3]; P<0.001) in patients without myocardial hemorrhage. Alternatively, in patients with myocardial hemorrhage, infarct zone edema was reduced at day 3 (T2, in ms: 51.8 [SD 4.6]; P<0.001), depicting a bimodal pattern. Left ventricular end-diastolic volume increased from baseline to 7 months in patients with myocardial hemorrhage (P=0.001) but not in patients without hemorrhage (P=0.377). The temporal evolutions of myocardial hemorrhage and edema are unimodal, whereas infarct zone edema (T2 value) has a bimodal pattern. Myocardial hemorrhage is prognostically important and represents a target for

  11. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    SciTech Connect

    Chen, Lijuan; Wang, Yingjie; Pan, Yaohua; Zhang, Lan; Shen, Chengxing; Qin, Gangjian; Ashraf, Muhammad; Weintraub, Neal; Ma, Genshan; Tang, Yaoliang

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  12. Cardioprotective Effects of Astragalin against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart

    PubMed Central

    Qu, Daoxu; Ren, Huanhuan; Yang, Wenxiao; Zhang, Xinjie; Zheng, Qiusheng; Wang, Dong

    2016-01-01

    This study aims to evaluate the cardioprotective effects of astragalin against myocardial ischemia/reperfusion (I/R) injury in isolated rat heart. The cardioprotective effects of astragalin on myocardial I/R injury were investigated on Langendorff apparatus. Adult male Sprague-Dawley rats were randomly divided into five groups. The results showed that astragalin pretreatment improved myocardial function. Compared with I/R group, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in coronary flow decreased in astragalin pretreatment groups, whereas superoxide dismutase (SOD) activity and glutathione/glutathione disulfide (GSH/GSSG) ratio significantly increased. The levels of malondialdehyde (MDA), intracellular reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) decreased in astragalin-treated groups. The infarct size (IS) and apoptosis rate in hearts from astragalin-treated groups were lower than those in hearts from the I/R group. Western blot analysis also revealed that astragalin preconditioning significantly reduced Bax level, whereas Bcl-2 was increased in the myocardium. Therefore, astragalin exhibited cardioprotective effects via its antioxidative, antiapoptotic, and anti-inflammatory activities. PMID:26788251

  13. Barbaloin pretreatment attenuates myocardial ischemia-reperfusion injury via activation of AMPK.

    PubMed

    Zhang, Peiyong; Liu, Xiaochen; Huang, Guotao; Bai, Caiyan; Zhang, Zhenling; Li, Hongjun

    2017-09-02

    Myocardial ischemia/reperfusion (MI/R) injury is a major cause of cardiac dysfunction during cardiovascular surgery and heart transplantation and characterized by hyperactive oxidative stress and inflammatory response. Barbaloin (BAR) is the main medicinal composition of the Chinese traditional medicine aloe vera. BAR has strong anti-oxidant, anti-inflammatory and anti-tumor properties. However, the effect of BAR on MI/R-induced myocardial injury is not explored. This study aims to investigate whether BAR provides cardio-protection against MI/R injury and the underlying mechanisms. BAR (20 mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for 5 days before MI/R operation. BAR pretreatment conferred cardio-protective effects against MI/R injury by improving hemodynamic function and limiting infarction size. Moreover, BAR pretreatment effectively inhibited I/R-induced myocardial oxidative stress and inflammatory response. Furthermore, BAR pretreatment activated adenosine monophosphate-activated protein kinase (AMPK) signaling in MI/R hearts. AMPK inhibitor compound C inhibited BAR-induced AMPK activation, and blunted BAR-mediated anti-oxidative, anti-inflammatory effects and cardio-protection. Taken together our study has identified a novel function of BAR and provided a molecular basis for BAR potential applications in the treatment of MI/R injury and other ischemic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Myocardial Bridge and Acute Plaque Rupture

    PubMed Central

    Perl, Leor; Daniels, David; Schwartz, Jonathan; Tanaka, Shige; Yeung, Alan; Tremmel, Jennifer A.; Schnittger, Ingela

    2016-01-01

    A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered. PMID:28251167

  15. Nanog expression in heart tissues induced by acute myocardial infarction.

    PubMed

    Luo, Huanhuan; Li, Qiong; Pramanik, Jogen; Luo, Jiankai; Guo, Zhikun

    2014-10-01

    Nanog is a potential stem cell marker and is considered a regeneration factor during tissue repair. In the present study, we investigated expression patterns of nanog in the rat heart after acute myocardial infarction by semi-quantitative RT-PCR, immunohistochemistry and Western blot analyses. Our results show that nanog at both mRNA and protein levels is positively expressed in myocardial cells, fibroblasts and small round cells in different myocardial zones at different stages after myocardial infarction, showing a spatio-temporal and dynamic change. After myocardial infarction, the nanog expression in fibroblasts and small round cells in the infarcted zone (IZ) is much stronger than that in the margin zone (MZ) and remote infarcted zone (RIZ). From day 7 after myocardial infarction, the fibroblasts and small cells strongly expressed nanog protein in the IZ, and a few myocardial cells in the MZ and the RIZ and the numbers of nanog-positive fibroblasts and small cells reached the highest peak at 21 days after myocardial infarction, but in this period the number of nanog-positive myocardial cells decreased gradually. At 28 days after myocardial infarction, the numbers of all nanog-positive cells decreased into a low level. Therefore, our data suggest that all myocardial cells, fibroblasts and small round cells are involved in myocardial reconstruction after cardiac infarction. The nanog-positive myocardial cells may respond to early myocardial repair, and the nanog-positive fibroblasts and small round cells are the main source for myocardial reconstruction after cardiac infarction.

  16. DJ-1 protects against cell death following acute cardiac ischemia-reperfusion injury.

    PubMed

    Dongworth, R K; Mukherjee, U A; Hall, A R; Astin, R; Ong, S-B; Yao, Z; Dyson, A; Szabadkai, G; Davidson, S M; Yellon, D M; Hausenloy, D J

    2014-02-27

    Novel therapeutic targets are required to protect the heart against cell death from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia-reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in HL-1 cardiac cells conferred the following beneficial effects: reduced cell death following simulated IRI (30.4±4.7% with DJ-1 versus 52.9±4.7% in control; n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening (a critical mediator of cell death) (260±33 s with DJ-1 versus 121±12 s in control; n=6, P<0.05); and induction of mitochondrial elongation (81.3±2.5% with DJ-1 versus 62.0±2.8% in control; n=6 cells, P<0.05). These beneficial effects of DJ-1 were absent in cells expressing the non-functional DJ-1(L166P) and DJ-1(Cys106A) mutants. Adult mice devoid of DJ-1 (KO) were found to be more susceptible to cell death from in vivo IRI with larger myocardial infarct sizes (50.9±3.5% DJ-1 KO versus 41.1±2.5% in DJ-1 WT; n≥7, P<0.05) and resistant to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased mitochondrial fragmentation on electron microscopy, although there were no differences in calcium-induced MPTP opening, mitochondrial respiratory function or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart from acute IRI cell death by preventing mitochondrial dysfunction. We propose that DJ-1 may represent a novel therapeutic target for cardioprotection.

  17. Acute myocardial infarct imaging with indium-111-labeled monoclonal antimyosin Fab

    SciTech Connect

    Khaw, B.A.; Yasuda, T.; Gold, H.K.; Leinbach, R.C.; Johns, J.A.; Kanke, M.; Barlai-Kovach, M.; Strauss, H.W.; Haber, E.

    1987-11-01

    Indium-111 monoclonal antimyosin Fab scintigraphy was used to detect myocardial necrosis in 52 of 54 patients (96.3%) with acute myocardial infarction. Infarcts were visualized when coronary arteries were persistently occluded (n = 10), became patent after thrombolysis (n = 33), or became patent after spontaneous reperfusion (n = 7). Posteroinferolateral visualizations were obtained in two patients with clinical and enzymatic evidence of infarction but normal electrocardiograms. Of the two patients in whom no infarcts were visualized, one had an anterior myocardial infarct. This patient underwent successful thrombolytic therapy, with attendant minimization of creatine kinase release. The other patient had a small, nonreperfused inferior myocardial infarct. Five patients with a history of remote infarction and acute necrosis showed antimyosin uptake only in regions concordant with the acute episodes of infarction, and radiolabeled antimyosin Fab localized in neither old infarcts nor normal, noninfarcted myocardium. Antimyosin Fab scintigraphy, thus, appears to be a highly specific means of delineating necrotic myocardium, at least in this limited and selected group of patients.

  18. Dual energy CT with nonlinear image blending improves visualization of delayed myocardial contrast enhancement in acute myocardial infarction.

    PubMed

    Kartje, Julia Katharina; Schmidt, Bernhard; Bruners, Philipp; Mahnken, Andreas H

    2013-01-01

    The objective of this study was to evaluate the effect of, and optimal parameters for, nonlinear image blending compared with linear image blending in the late-phase dual energy computed tomography (DECT) for the visualization of delayed myocardial contrast enhancement in acute myocardial infarction (MI). Acute reperfused MI was induced in 7 pigs by temporary occlusion of the left anterior descending or the left circumflex artery. Two hours after the reperfusion, a contrast-enhanced, late-phase DECT (80 kV/140 kV) scanning was performed. The DECT data were postprocessed with linear and nonlinear image blending techniques. Contrast and percentage signal differences between healthy and infarcted myocardium as well as the blood pool of the left ventricle were computed for the linear and nonlinear techniques and the low- and high-kilovolt images. Data were compared using repeated-measures analysis of variance and post hoc t tests. The nonlinear blending showed the highest signal differences for all contrasts and analyses. Repeated-measures ANOVA results confirmed that the differences were statistically significant for the different postprocessing techniques (P value ranging from <0.001-0.003). Paired-samples post hoc t tests proved the significance of these results (P value ranging from <0.001-0.037). The ideal settings for the nonlinear image blending can thus be deduced from the computed tomographic values of the regions of interest in the linearly blended images with the weighting factor 0.3. Nonlinear image blending improves the visualization of acute MI in the late-phase DECT. It is superior to linearly blended images and source images obtained at 80 or 140 kV.

  19. Clinical efforts to reduce myocardial infarct size--the next step.

    PubMed

    Braunwald, Eugene

    2011-01-01

    Prompt myocardial reperfusion reduces infarct size in patients experiencing coronary occlusion. However, its clinical value is limited because reperfusion also causes ischemic myocardial reperfusion injury (IMRI). Considerable research to reduce IMRI has been conducted. Three interventions appear to be promising: 1) myocardial conditioning, which consists of repetitive occlusions of coronary or other arteries prior to or at the time of myocardial reperfusion; 2) the administration of cyclosporine A; and 3) the administration of adenosine. A plan for the testing of these interventions in patients with acute myocardial infarction is described.

  20. Prehospital delay and time to reperfusion therapy in ST elevation myocardial infarction

    PubMed Central

    George, Linsha; Ramamoorthy, Lakshmi; Satheesh, Santhosh; Saya, Rama Prakasha; Subrahmanyam, D. K. S.

    2017-01-01

    Background: Despite efforts aimed at reducing the prehospital delay and treatment delay, a considerable proportion of patients with ST elevation myocardial infarction (STEMI) present late and receive the reperfusion therapy after unacceptably long time periods. This study aimed at finding out the patients' decision delay, prehospital delay, door-to-electrocardiography (ECG), door-to-needle, and door-to-primary percutaneous coronary intervention (PCI) times and their determinants among STEMI patients. Materials and Methods: A cross-sectional study conducted among 96 patients with STEMI admitted in a tertiary care center in South India. The data were collected using interview of the patients and review of records. The distribution of the data was assessed using Kolmogorov–Smirnov test, and the comparisons of the patients' decision delay, prehospital delay, and time to start reperfusion therapy with the different variables were done using Mann–Whitney U-test or Kruskal–Wallis test based on the number of groups. Results: The mean (standard deviation) and median (range) age of the participants were 55 (11) years and 57 (51) years, respectively. The median patients' decision delay, prehospital delay, door-to-ECG, door-to-needle, and door-to-primary PCI times were 75, 290, 12, 75, 110 min, respectively. Significant factors associated (P < 0.05) with patients' decision delay were alcoholism, symptom progression, and attempt at symptom relief measures at home. Prehospital delay was significantly associated (P < 0.05) with domicile, difficulty in arranging money, prior consultation at study center, place of symptom onset, symptom interpretation, and mode of transportation. Conclusions: The prehospital delay time among the South Indian population is still unacceptably high. Public education, improving the systems of prehospital care, and measures to improve the patient flow and management in the emergency department are essentially required. The time taken to take ECG

  1. Activity Exerted by a Testosterone Derivative on Myocardial Injury Using an Ischemia/Reperfusion Model

    PubMed Central

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Betty, Sarabia-Alcocer; Monica, Velázquez-Sarabia Betty

    2014-01-01

    Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R). Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increases (P = 0.05) the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001–100 nM); however, this phenomenon was significantly inhibited (P = 0.06) by indomethacin and PINANE-TXA2  (P = 0.05) at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation. PMID:24839599

  2. Activity exerted by a testosterone derivative on myocardial injury using an ischemia/reperfusion model.

    PubMed

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Betty, Sarabia-Alcocer; Monica, Velázquez-Sarabia Betty

    2014-01-01

    Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R). Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increases (P = 0.05) the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited (P = 0.06) by indomethacin and PINANE-TXA2  (P = 0.05) at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation.

  3. Effects of Nitrate Intake on Myocardial Ischemia-Reperfusion Injury in Diabetic Rats.

    PubMed

    Jeddi, Sajad; Khalifi, Saeedeh; Ghanbari, Mahboubeh; Bageripour, Fatemeh; Ghasemi, Asghar

    2016-10-01

    Coronary artery disease is 2-3 times more common in diabetic individuals. Dietary nitrate/nitrite has beneficial effects in both diabetes and cardiovascular disease. It also has protective effects against myocardial ischemia-reperfusion (IR) injury in healthy animals. However, the effects of nitrate on myocardial IR injury in diabetic rats have not yet been investigated. We examined the effects of dietary nitrate on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats. Rats were divided into four groups (n=7 in each group): control, control+nitrate, diabetes, and diabetes+nitrate. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Nitrate (sodium nitrate) was added to drinking water (100 mg/L) for 2 months. The hearts were perfused in a Langendorff apparatus at 2 months and assessed before (baseline) and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP), minimum and maximum rates of pressure change in the left ventricle (±dP/dt), endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression, and levels of malondialdehyde (MDA) and NO metabolites (NOx). Recovery of LVDP and ±dP/dt was lower in diabetic rats versus controls, but almost normalized after nitrate intake. Diabetic rats had lower eNOS and higher iNOS expression both at baseline and after IR, and dietary nitrate restored these parameters to normal values after IR. Compared with controls, heart NOx level was lower in diabetic rats at baseline but was higher after IR. Diabetic rats had higher MDA levels both at baseline and after IR, which along with heart NOx levels decreased following nitrate intake. Dietary nitrate in diabetic rats provides cardioprotection against IR injury by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart.

  4. Effects of Nitrate Intake on Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

    PubMed Central

    Jeddi, Sajad; Khalifi, Saeedeh; Ghanbari, Mahboubeh; Bageripour, Fatemeh; Ghasemi, Asghar

    2016-01-01

    Background Coronary artery disease is 2-3 times more common in diabetic individuals. Dietary nitrate/nitrite has beneficial effects in both diabetes and cardiovascular disease. It also has protective effects against myocardial ischemia-reperfusion (IR) injury in healthy animals. However, the effects of nitrate on myocardial IR injury in diabetic rats have not yet been investigated. Objective We examined the effects of dietary nitrate on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats. Method Rats were divided into four groups (n=7 in each group): control, control+nitrate, diabetes, and diabetes+nitrate. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Nitrate (sodium nitrate) was added to drinking water (100 mg/L) for 2 months. The hearts were perfused in a Langendorff apparatus at 2 months and assessed before (baseline) and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP), minimum and maximum rates of pressure change in the left ventricle (±dP/dt), endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression, and levels of malondialdehyde (MDA) and NO metabolites (NOx). Results Recovery of LVDP and ±dP/dt was lower in diabetic rats versus controls, but almost normalized after nitrate intake. Diabetic rats had lower eNOS and higher iNOS expression both at baseline and after IR, and dietary nitrate restored these parameters to normal values after IR. Compared with controls, heart NOx level was lower in diabetic rats at baseline but was higher after IR. Diabetic rats had higher MDA levels both at baseline and after IR, which along with heart NOx levels decreased following nitrate intake. Conclusion Dietary nitrate in diabetic rats provides cardioprotection against IR injury by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart. PMID:27849257

  5. Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-Reperfusion

    PubMed Central

    Vreeswijk-Baudoin, Inge; Groot, Hilde E.; van de Kolk, Kees W. A.; de Boer, Rudolf A.; Mateo Leach, Irene; Vliegenthart, Rozemarijn; Sillje, Herman H. W.; van der Harst, Pim

    2016-01-01

    Background Interleukin-6 (IL-6) levels are upregulated in myocardial infarction. Recent data suggest a causal role of the IL-6 receptor (IL-6R) in coronary heart disease. We evaluated if IL-6R blockade by a monoclonal antibody (MR16-1) prevents the heart from adverse left ventricular remodeling in a mouse model of ischemia-reperfusion (I/R). Methods CJ57/BL6 mice underwent I/R injury (left coronary artery ligation for 45 minutes) or sham surgery, and thereafter received MR16-1 (2mg/mouse) 5 minutes before reperfusion and 0.5mg/mouse weekly during four weeks, or control IgG treatment. Cardiac Magnetic Resonance Imaging (CMR) and hemodynamic measurements were performed to determine cardiac function after four weeks. Results I/R caused left ventricular dilatation and a decrease in left ventricular ejection fraction (LVEF). However, LVEF was significantly lower in the MR16-1 treatment group compared to the IgG group (28±4% vs. 35±6%, p = 0.02; sham 45±6% vs. 43±4%, respectively; p = NS). Cardiac relaxation (assessed by dP/dT) was not significantly different between the MR16-1 and IgG groups. Also, no differences were observed in histological myocardial fibrosis, infarct size and myocyte hypertrophy between the groups. Conclusion Blockade of the IL-6R receptor by the monoclonal MR16-1 antibody for four weeks started directly after I/R injury did not prevent the process of cardiac remodeling in mice, but rather associated with a deterioration in the process of adverse cardiac remodeling. PMID:27936014

  6. Activation of Adenosine Triphosphate-regulated Potassium Channels during Reperfusion Restores Isoflurane Postconditioning-induced Cardiac Protection in Acutely Hyperglycemic Rabbits.

    PubMed

    Raphael, Jacob; Gozal, Yaacov; Navot, Nachum; Zuo, Zhiyi

    2015-06-01

    Hyperglycemia is known to inhibit myocardial anesthetic postconditioning. The authors tested whether activation of adenosine triphosphate-regulated potassium (KATP) channels would restore anesthetic postconditioning during acute hyperglycemia. Rabbits subjected to 40-min myocardial ischemia and 3-h reperfusion (ischemia-reperfusion [I/R]) were assigned to groups (n = 10 in each group) with or without isoflurane postconditioning (2.1% for 5 min) in the presence or absence of hyperglycemia and/or the KATP channel agonist diazoxide. Creatine kinase MB fraction and infarct size were measured. Phosphorylated protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were assessed. Oxidative stress was evaluated by measuring malondialdehyde, and apoptosis was assessed by dUTP nick-end labeling and activated caspase-3. Postconditioning significantly reduced myocardial infarct size (26 ± 4% in the isoflurane [ISO] group vs. 53 ± 2% in the I/R group; P = 0.007); whereas, hyperglycemia inhibited this effect (infarct size: 47 ± 2%, P = 0.02 vs. the ISO group). Phosphorylated and eNOS levels increased, whereas malondialdehyde and myocardial apoptosis were significantly lower after isoflurane postconditioning compared with I/R. These effects were inhibited by acute hyperglycemia. Diazoxide restored the protective effect of isoflurane in the hyperglycemic animals (infarct size: 29 ± 2%; P = 0.01 vs. the I/R group), reduced malondialdehyde levels and myocardial apoptosis, but did not affect the expression of phosphorylated Akt or eNOS. KATP channel activation restored anesthetic postconditioning-induced myocardial protection under acute hyperglycemia. This effect occurred without increasing Akt or eNOS phosphorylation, suggesting that KATP channels are located downstream to Akt and eNOS in the pathway of isoflurane-induced myocardial postconditioning.

  7. The feasibility of imaging myocardial ischemic/reperfusion injury using 99mTc-labeled duramycin in a porcine model

    PubMed Central

    Wang, Lei; Wang, Feng; Fang, Wei; Johnson, Steven E.; Audi, Said; Zimmer, Michael; Holly, Thomas A; Lee, Daniel; Zhu, Bao; Zhu, Haibo; Zhao, Ming

    2015-01-01

    When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. 99mTc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of 99mTc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia-reperfusion injury. Methods The clearance and distribution of intravenously injected 99mTc-duramycin were characterized in sham-operated animals (n = 5). In a closed chest model of myocardial ischemia, coronary occlusion was induced by balloon angioplasty (n = 9). 99mTc-duramycin (10-15 mCi) was injected intravenously at 1 hour after reperfusion. SPECT/CT was acquired at 1 and 3 hours after injection. Cardiac tissues were analyzed for changes associated with acute cellular injuries. Autoradiography and gamma counting was used to determine radioactivity uptake. For the remaining animals, 99mTc-tetrafosamin scan was performed on the second day to identify the infarct site. Results Intravenously injected 99mTc-duramycin cleared from circulation predominantly via the renal/urinary tract with an α-phase half-life of 3.6 ± 0.3 minutes and β-phase half-life of 179.9 ± 64.7 minutes. In control animals, the ratios between normal heart and lung were 1.76 ± 0.21, 1.66 ± 0.22, 1.50 ± 0.20 and 1.75 ± 0.31 at 0.5, 1, 2 and 3 hours post injection, respectively. The ratios between normal heart and liver were 0.88 ± 0.13, 0.80 ± 0.13, 0.82 ± 0.19 and 0.88 ± 0.14. In vivo visualization of focal radioactivity uptake in the ischemic heart was attainable as early as 30 min post injection. The in vivo ischemic-to-normal uptake ratios were 3.57 ± 0.74 and 3.69 ± 0.91 at 1 and 3 hours post injection, respectively. Ischemic-to-lung ratios were 4.89 ± 0.85 and 4.93 ± 0.57; and ischemic-to-liver ratios were 2.05 ± 0.30 to 3.23 ± 0

  8. The feasibility of imaging myocardial ischemic/reperfusion injury using (99m)Tc-labeled duramycin in a porcine model.

    PubMed

    Wang, Lei; Wang, Feng; Fang, Wei; Johnson, Steven E; Audi, Said; Zimmer, Michael; Holly, Thomas A; Lee, Daniel C; Zhu, Bao; Zhu, Haibo; Zhao, Ming

    2015-02-01

    When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. (99m)Tc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of (99m)Tc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia-reperfusion injury. The clearance and distribution of intravenously injected (99m)Tc-duramycin were characterized in sham-operated animals (n=5). In a closed chest model of myocardial ischemia, coronary occlusion was induced by balloon angioplasty (n=9). (99m)Tc-duramycin (10-15mCi) was injected intravenously at 1hour after reperfusion. SPECT/CT was acquired at 1 and 3hours after injection. Cardiac tissues were analyzed for changes associated with acute cellular injuries. Autoradiography and gamma counting were used to determine radioactivity uptake. For the remaining animals, (99m)Tc-tetrafosamin scan was performed on the second day to identify the infarct site. Intravenously injected (99m)Tc-duramycin cleared from circulation predominantly via the renal/urinary tract with an α-phase half-life of 3.6±0.3minutes and β-phase half-life of 179.9±64.7minutes. In control animals, the ratios between normal heart and lung were 1.76±0.21, 1.66±0.22, 1.50±0.20 and 1.75±0.31 at 0.5, 1, 2 and 3hours post-injection, respectively. The ratios between normal heart and liver were 0.88±0.13, 0.80±0.13, 0.82±0.19 and 0.88±0.14. In vivo visualization of focal radioactivity uptake in the ischemic heart was attainable as early as 30min post-injection. The in vivo ischemic-to-normal uptake ratios were 3.57±0.74 and 3.69±0.91 at 1 and 3hours post-injection, respectively. Ischemic-to-lung ratios were 4.89±0.85 and 4.93±0.57; and ischemic-to-liver ratios were 2.05±0.30 to 3.23±0.78. The size of (99m)Tc-duramycin positive

  9. Captopril Pretreatment Produces an Additive Cardioprotection to Isoflurane Preconditioning in Attenuating Myocardial Ischemia Reperfusion Injury in Rabbits and in Humans.

    PubMed

    Tian, Yi; Li, Haobo; Liu, Peiyu; Xu, Jun-mei; Irwin, Michael G; Xia, Zhengyuan; Tian, Guogang

    2015-01-01

    Pretreatment with the angiotensin-converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R) injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso) may additively or synergistically attenuate MI/R injury. Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control), captopril pretreatment for 3 days (Cap3d), or single dose captopril (Cap1hr, 1 hour) before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso). Rabbit MI/R model was induced by occluding coronary artery for 30 min followed by 2-hour reperfusion. Rabbits were randomized to receive sham operation (Sham), MI/R (I/R), captopril (Cap, 24 hours before MI/R), Iso, or the combination of captopril and Iso (Iso+Cap). In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress. A joint use of 3-day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation.

  10. Captopril Pretreatment Produces an Additive Cardioprotection to Isoflurane Preconditioning in Attenuating Myocardial Ischemia Reperfusion Injury in Rabbits and in Humans

    PubMed Central

    Tian, Yi; Liu, Peiyu; Xu, Jun-mei; Irwin, Michael G.; Xia, Zhengyuan; Tian, Guogang

    2015-01-01

    Background. Pretreatment with the angiotensin-converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R) injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso) may additively or synergistically attenuate MI/R injury. Methods and Results. Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control), captopril pretreatment for 3 days (Cap3d), or single dose captopril (Cap1hr, 1 hour) before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso). Rabbit MI/R model was induced by occluding coronary artery for 30 min followed by 2-hour reperfusion. Rabbits were randomized to receive sham operation (Sham), MI/R (I/R), captopril (Cap, 24 hours before MI/R), Iso, or the combination of captopril and Iso (Iso+Cap). In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress. Conclusion. A joint use of 3-day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation. PMID:26273143

  11. Cardioprotective Effect of Aloe vera Biomacromolecules Conjugated with Selenium Trace Element on Myocardial Ischemia-Reperfusion Injury in Rats.

    PubMed

    Yang, Yang; Yang, Ming; Ai, Fen; Huang, Congxin

    2017-06-01

    The present study was undertaken to evaluate the cardioprotection potential and underlying molecular mechanism afforded by a selenium (Se) polysaccharide (Se-AVP) from Aloe vera in the ischemia-reperfusion (I/R) model of rats in vivo. Myocardial I/R injury was induced by occluding the left anterior descending coronary artery (LAD) for 30 min followed by 2-h continuous reperfusion. Pretreatment with Se-AVP (100, 200, and 400 mg/kg) attenuated myocardial damage, as evidenced by reduction of the infarct sizes, increase in serum and myocardial endogenous antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT)), and decrease in the malondialdehyde (MDA) level in the rats suffering I/R injury. This cardioprotective activity afforded by Se-AVP is further supported by the decreased levels of cardiac marker enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as the rise of myocardial Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in I/R rats. Additionally, cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining and the result showed that the percent of TUNEL-positive cells in myocardium of Se-AVP-treated groups was lower than I/R rats. In conclusion, we clearly demonstrated that Se-AVP had a protective effect against myocardial I/R injury in rats by augmenting endogenous antioxidants and protecting rat hearts from oxidative stress-induced myocardial apoptosis.

  12. The cardioprotective effects of citric Acid and L-malic Acid on myocardial ischemia/reperfusion injury.

    PubMed

    Tang, Xilan; Liu, Jianxun; Dong, Wei; Li, Peng; Li, Lei; Lin, Chengren; Zheng, Yongqiu; Hou, Jincai; Li, Dan

    2013-01-01

    Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components of Fructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. In in vivo rat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-α, and platelet aggregation. In vitro experiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient of Fructus Choerospondiatis responsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease.

  13. Geranylgeranylacetone protects against myocardial ischemia and reperfusion injury by inhibiting high-mobility group box 1 protein in rats.

    PubMed

    Wang, Neng; Min, Xinwen; Li, Dongfeng; He, Peigen; Zhao, Libin

    2012-02-01

    The high mobility group box 1 (HMGB1) protein plays an important role in myocardial ischemia and reperfusion (I/R) injury. Geranylgeranylacetone (GGA), a heat shock protein 72 inducer, has been reported to reduce myocardial I/R injury. The aim of this study was to investigate the cardioprotective mechanism of GGA during myocardial I/R injury in rats. Anesthetized male rats were treated once with GGA (200 mg/kg, p.o.) 24 h before ischemia, and subjected to ischemia for 30 min, followed by reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) activity and infarct size were measured. HMGB1 expression was assessed by immunoblotting. The results showed that pre-treatment with GGA (200 mg/kg) significantly reduced the infarct size and the levels of LDH and CK after 4 h of reperfusion (all P<0.05). GGA also significantly inhibited the increase in MDA levels and the decrease in SOD levels (both P<0.05). Meanwhile, GGA considerably suppressed the expression of HMGB1 induced by I/R. The present study suggests that GGA is capable of attenuating myocardial I/R injury by inhibiting HMGB1 expression.

  14. All-Trans Retinoic Acid Ameliorates Myocardial Ischemia/Reperfusion Injury by Reducing Cardiomyocyte Apoptosis.

    PubMed

    Zhu, Zhengbin; Zhu, Jinzhou; Zhao, Xiaoran; Yang, Ke; Lu, Lin; Zhang, Fengru; Shen, Weifeng; Zhang, Ruiyan

    2015-01-01

    Myocardial ischemia/reperfusion (I/R) injury interferes with the restoration of blood flow to ischemic myocardium. Oxidative stress-elicited apoptosis has been reported to contribute to I/R injury. All-trans retinoic acid (ATRA) has anti-apoptotic activity as previously reported. Here, we investigated the effects and the mechanism of action of ATRA on myocardial I/R injury both in vivo and in vitro. In vivo, ATRA reduced the size of the infarcted area (17.81±1.05% vs. 24.41±1.03%, P<0.05) and rescued cardiac function loss (ejection fraction 46.42±6.76% vs. 37.18±4.63%, P<0.05) after I/R injury. Flow-cytometric analysis and TUNEL assay demonstrated that the protective role of ATRA on myocardial I/R injury was related to its anti-apoptotic effects. The anti-apoptotic effects of ATRA were associated with partial inhibition of reactive oxygen species (ROS) production and significantly less phosphorylation of mitogen-activated protein kinases (MAPKs) including p38, JNK, and ERK. Western blot analysis also revealed that ATRA pre-treatment increased a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) expression (0.65 ± 0.20 vs. 0.41±0.02 in vivo) and reduced the level of receptor for advanced glycation end-products (RAGE) (0.38 ± 0.17 vs. 0.52 ± 0.11 in vivo). Concomitantly, the protective role of ATRA on I/R injury was not observed in RAGE-KO mice. The current results indicated that ATRA could prevent myocardial injury and reduced cardiomyocyte apoptosis after I/R effectively. One possible mechanism underlying these effects is that ATRA could increase ADAM10 expression and thus cleave RAGE, which is the main receptor up-stream of MAPKs in myocardial I/R injury, resulting in the down-regulation of MAPK signaling and protective role on myocardial I/R injury.

  15. Protective Effects of Co-Administration of Gallic Acid and Cyclosporine on Rat Myocardial Morphology Against Ischemia/Reperfusion

    PubMed Central

    Dianat, Mahin; Sadeghi, Najmeh; Badavi, Mohammad; Panahi, Marziyeh; Taheri Moghadam, Mahin

    2014-01-01

    Background: Irreversible myocardial ischemic injury begins 20 minutes after the onset of coronary occlusion. Then the infarcted cells show signs of necrosis and death. Objectives: This study investigated the effects of co-administration of Gallic acid (antioxidant) with cyclosporine (mitochondrial permeability transition pore [mPTP] inhibitor) on myocardial morphology of rats during ischemia and reperfusion. Materials and Methods: Fifty-four male Wistar rats (250-300 g), were randomly divided into 9 groups: sham, control (Ca received saline, 1 mL/kg, Cb: perfused with cyclosporine CsA 0.2 µM), 3 groups pretreated with Gallic acid in saline (G1a:7.5, G2a:15, and G3a: 30 mg/kg/day, and gavage daily for 10 days, n = 6), and the other three groups were pretreated with Gallic acid then perfused using CsA, (G1b:7.5, G2b:15, and G3b: 30 mg/kg/day) at the first 13 minutes of reperfusion period. After 10 days pretreatment, the rat hearts were isolated and transferred to Langendorff apparatus and exposed to 30 minutes ischemia following 60 minutes reperfusion. Afterward, the hearts were preserved in 10% formalin for histological studies at the end of the experiment. Finally, hematoxylin and eosin and Masson’s trichrome staining techniques were used for evaluating the changes in myocardial architecture, degradation of myofibers, and collagen integrity. The differences were analyzed using Pearson test. Results: Cell degenerative changes, pyknotic nuclei, contraction bands, edema, and loosening of collagen in between muscle fibers were observed during ischemia-reperfusion. Myocardial architecture and cellular morphology were recovered in co-administration groups, especially in (Gallic acid 15 mg/kg + CsA, P < 0.001). Conclusions: The results suggest the important role of the antioxidant system potentiation in the prevention of myocardial damage. PMID:25625048

  16. Taxol prevents myocardial ischemia-reperfusion injury by inducing JNK-mediated HO-1 expression.

    PubMed

    Cao, Huaming; Wang, Yiping; Wang, Qiang; Wang, Ruxing; Guo, Suxia; Zhao, Xiaoxi; Zhang, Yu; Tong, Debing; Yang, Zhenyu

    2016-01-01

    Ischemia/hypoxia and reperfusion impair mitochondria and produce a large amount of reactive oxygen species (ROS), which lead to mitochondrial and brain damage. Furthermore, heme oxygenase-1 (HO-1) as a cytoprotective gene protects cells against ROS-induced cell death in ischemia-reperfusion injury. Induction of HO-1 is involved in cytoprotective effects of taxol. We hypothesize that taxol protects cardiac myocytes possibly by preserving myocardial mitochondrial function and inducing HO-1 expression through the JNK pathway. In this project, the perfused Langendorff hearts isolated from rats were randomly divided into five groups: control, ischemic, ischemic + taxol (0.1 μM), ischemic + taxol (0.3 μM), and ischemic + taxol (1 μM). Briefly, following a 15 min equilibration period, the control group was subject to normoxic perfusion for 120 min; the ischemia group, normoxic reperfusion for 120 min after 30 min ischemia; the taxol groups, normoxic reperfusion for 120 min after 30-min ischemia with taxol (0.1, 0.3, or 1 μM). The microtubule disruption score, ROS levels, and the activity of mitochondrial electron transport chain complexes I and III were examined by using immunohistochemical methods and free radical detection kits. Western blot assay was employed to study the underlying mechanisms. After Taxol treatment (0.1 µM), the ischemic microtubule disruption score was reduced to 9.8 ± 1.9%. The study revealed that 0.1, 0.3, and 1 μM taxol reduced the level of ROS by 33, 46 and 51%, respectively (p < 0.05). In additional, 0.3 and 1 μM taxol dramatically increased the activity of mitochondrial electron transport chain complex I (99.11 ± 2.59, 103.49 ± 3.89) and mitochondrial electron transport chain complex III (877.82 ± 12.08; 907.42 ± 16.21; 914.73 ± 19.39, *p < 0.05). Additionally, phosphorylation levels of JNK1 were significantly increased in the taxol group. Furthermore, the

  17. Capsaicin, arterial hypertensive crisis and acute myocardial infarction associated with high levels of thyroid stimulating hormone.

    PubMed

    Patanè, Salvatore; Marte, Filippo; Di Bella, Gianluca; Cerrito, Marco; Coglitore, Sebastiano

    2009-05-01

    Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene-related peptide (CGRP) is stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. It has been reported that capsaicin pretreatment deplete cardiac C-fiber peptide stores. Furthermore, it has also been reported that capsaicin-treated pigs significantly increase mean arterial blood pressure compared with controls and that the decrease in CGRP synthesis and release contributes to the elevated blood pressure. It has also been reported that sub-clinical hypothyroidism is associated with a significant risk of coronary heart disease (CHD). We present a case of arterial hypertensive crisis and acute myocardial infarction in a 59-year-old Italian man with high levels of thyroid stimulating hormone and with an abundant ingestion of peppers and of chili peppers which occurred the day before.

  18. The use of reperfusion and revascularization procedures in acute coronary syndrome in Portugal: a systematic review.

    PubMed

    Lopes-Conceição, Luísa; Pereira, Marta; Araújo, Carla; Laszczýnska, Olga; Lunet, Nuno; Azevedo, Ana

    2014-11-01

    Reperfusion and revascularization therapies play an important role in the management of coronary heart disease and have contributed to decreases in case fatality rates. We aimed to describe the use of these therapies for the treatment of acute coronary syndrome (ACS) patients over time in Portugal. PubMed was searched in July 2012. The proportion of patients treated with fibrinolysis, primary percutaneous coronary intervention (PCI), any PCI and coronary artery bypass grafting (CABG) was described according to type of ACS: STEMI (≥90% patients with ST-segment elevation or Q-wave myocardial infarction), NSTE-ACS (≥90% patients with non-ST-segment elevation ACS) and mixed ACS (all others). We identified 41 eligible studies, published between 1989 and 2011. Twenty-eight reported on samples considered representative of ACS patients treated in Portugal. The small number of estimates of the use of each treatment in STEMI and NSTE-ACS patients precluded identification of any time trend. In the last 20 years, the proportion of mixed ACS patients treated with fibrinolysis decreased and the use of PCI increased, while the use of CABG did not change. The general pattern of the use of reperfusion and revascularization is in accordance with that reported in other developed countries, reflecting a favorable trend in the quality of care of ACS patients. The relatively small number of estimates on the same procedure in comparable patients limits the generalizability of the conclusions, and highlights the need for systematic approaches to monitor the use of treatments over time. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  19. 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.

  20. Mst1-mediated phosphorylation of Bcl-xL is required for myocardial reperfusion injury

    PubMed Central

    Zhai, Peiyong; Del Re, Dominic P.; Maejima, Yasuhiro

    2016-01-01

    Mst1 is a central Ser-Thr kinase in the Hippo pathway, which promotes apoptosis and inhibits cell proliferation. We have shown previously that, in cardiomyocytes, oxidative stress activates Mst1 at mitochondria, where Mst1 phosphorylates Bcl-xL at Ser14, inducing dissociation of Bcl-xL from Bax and thereby promoting apoptosis. However, the functional significance of Ser14 phosphorylation of endogenous Bcl-xL in vivo remains elusive. We generated knockin (KI) mice in which Ser14 of Bcl-xL is replaced with Ala. KI mice were born at the expected Mendelian ratio, and adult KI mice exhibited normal cardiac morphology and function at baseline. However, KI mice were protected from myocardial ischemia/reperfusion (I/R) injury and exhibited reduced cardiomyocyte apoptosis. Although suppression of endogenous Mst1 also reduced I/R injury, there was no additive protective effect when Mst1 was inhibited in KI mice. The development of dilated cardiomyopathy induced by cardiac-specific overexpression of Mst1 was also ameliorated in KI mice. Lats2 and YAP, two other key components of the Hippo pathway, were not affected in KI mice. These results suggest that Ser14 phosphorylation of Bcl-xL plays an essential role in mediating both cardiomyocyte apoptosis and myocardial injury by acting as a key downstream mediator of Mst1 independently of the canonical Hippo pathway. PMID:27218122

  1. Intracoronary thallium-201 scintigraphy after thrombolytic therapy for acute myocardial infarction compared with 10 and 100 day intravenous thallium-201 scintigraphy

    SciTech Connect

    Heller, G.V.; Parker, J.A.; Silverman, K.J.; Royal, H.D.; Kolodny, G.M.; Paulin, S.; Braunwald, E.; Markis, J.E.

    1987-02-01

    Thallium-201 imaging has been utilized to estimate myocardial salvage after thrombolytic therapy for acute myocardial infarction. However, results from recent animal studies have suggested that as a result of reactive hyperemia and delayed necrosis, thallium-201 imaging may overestimate myocardial salvage. To determine whether early overestimation of salvage occurs in humans, intracoronary thallium-201 scans 1 hour after thrombolytic therapy were compared with intravenous thallium-201 scans obtained approximately 10 and 100 days after myocardial infarction in 29 patients. In 10 patients with angiographic evidence of coronary reperfusion, immediate improvement in thallium defects and no interim clinical events, there was no change in imaging in the follow-up studies. Of nine patients with coronary reperfusion but no initial improvement of perfusion defects, none showed worsening of defects in the follow-up images. Six of these patients demonstrated subsequent improvement at either 10 or 100 days after infarction. Seven of 10 patients with neither early evidence of reperfusion nor improvement in perfusion defects had improvement of infarct-related perfusion defects, and none showed worsening. In conclusion, serial scanning at 10 and 100 days after infarction in patients with no subsequent clinical events showed no worsening of the perfusion image compared with images obtained in acute studies. Therefore, there is no evidence that thallium-201 imaging performed early in patients with acute myocardial infarction overestimates improvement.

  2. Pizza and risk of acute myocardial infarction.

    PubMed

    Gallus, S; Tavani, A; La Vecchia, C

    2004-11-01

    Pizza eating has been favourably related to the risk of cardiovascular disease, but the data are limited. To evaluate the potential role of pizza consumption on the risk of acute myocardial infarction (AMI), we considered data from an Italian study. We conducted a hospital-based case-control study on 507 cases of nonfatal AMI and 478 controls in Milan, Italy, between 1995 and 1999. The multivariate odds ratios were 0.78 for occasional, 0.62 for regular and 0.44 for frequent eaters. The estimates were similar across strata of age, sex, smoking and other major covariates. Some of the ingredients of pizza have been shown to have a favourable influence on the risk of cardiovascular disease. However, there is no single explanation for the present findings. Pizza may in fact represent a general indicator of Italian diet, that has been shown to have potential cardiovascular benefits.

  3. Acute prolongation of myocardial refractoriness by sotalol.

    PubMed Central

    Bennett, D H

    1982-01-01

    Sotalol, a beta adrenoceptor antagonist, was given intravenously to 15 patients with accessory atrioventricular pathways during intracardiac electrophysiological studies. Eleven patients had the Wolff-Parkinson-White syndrome and four patients had concealed left sided accessory pathways. Four patients were restudied while receiving oral sotalol. In contrast to the actions typical of beta blocking agents, intravenous sotalol prolonged the effective refractory periods of the ventricles and accessory pathways and reduced the ventricular response to atrial fibrillation in the patients with the Wolff-Parkinson-White syndrome. Similar results were obtained with oral administration. These findings support the observation that sotalol, unlike other beta blocking agents. causes acute prolongation of the myocardial action potential and suggest that this action might be of therapeutic use. PMID:7082500

  4. 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

  5. Oxygen Therapy in Suspected Acute Myocardial Infarction.

    PubMed

    Hofmann, Robin; James, Stefan K; Jernberg, Tomas; Lindahl, Bertil; Erlinge, David; Witt, Nils; Arefalk, Gabriel; Frick, Mats; Alfredsson, Joakim; Nilsson, Lennart; Ravn-Fischer, Annica; Omerovic, Elmir; Kellerth, Thomas; Sparv, David; Ekelund, Ulf; Linder, Rickard; Ekström, Mattias; Lauermann, Jörg; Haaga, Urban; Pernow, John; Östlund, Ollie; Herlitz, Johan; Svensson, Leif

    2017-08-28

    Background The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. Methods In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. Results A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. Conclusions Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart-Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110 .).

  6. Activation of volume-sensitive Cl− channel mediates autophagy-related cell death in myocardial ischaemia/reperfusion injury

    PubMed Central

    Li, Xing; Huo, Cong; Jia, Xin; Wang, Lin; Xu, Rong; Wang, Ning; Zhang, Mingming; Li, Hong; Wang, Xiaoming

    2016-01-01

    Excessive reactive oxygen species (ROS) plays an important role in myocardial ischemia/reperfusion (I/R) injury, which triggers not only myocardial cellular apoptosis but also autophagy-related cell death, in which volume-sensitive outwardly rectifying (VSOR) Cl− channel-activated by ROS contributes to cell apoptotic volume decrease, playing an incipient incident of cellular apoptosis. However, whether VSOR Cl− channel concurrently participates in autophagy-related cell death regulation remains unclear. To illuminate the issue, studies underwent in myocardial vitro and vivo I/R model. Rats were performed to ischemia 30 minutes and subsequent reperfusion 24-96 hours, ROS scavenger (NAC), VSOR Cl− channel blocker (DCPIB) and autophagy inhibitor (3MA) were administered respectively. Results showed that oxidative stress, LC3-II stain and inflammation in myocardial tissue were markedly increased, lysosome associated membrane protein-2 (LAMP2) were significantly reduced with I/R group as compared with sham group, reperfusion significantly led to damage in myocardial tissue and heart function, whereas the disorder could be rescued through these agents. Moreover, primary neonatal rat cardiomyocytes hypoxia/reoxygenation model were administered, results showed that VSOR Cl− channel-activated by reoxygenation could cause both cell volume decrease and intracellular acidification, which further increased LC3 and depleted of LAMP2, resulting in autophagy-related cell death. Interestingly, VSOR Cl− channel-blocked by DCPIB could stably maintain the cell volume, intracellular pH, abundant LAMP2 and autophagic intensity regardless of ROS intension derived from reoxygenation injury or adding H2O2. These results first demonstrate that VSOR Cl− channel-activated is a pivotal event to trigger autophagy-related death, which reveals a novel therapeutic target to decrease myocardial I/R injury. PMID:27322431

  7. SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury.

    PubMed

    Yang, Yang; Duan, Weixun; Lin, Yan; Yi, Wei; Liang, Zhenxing; Yan, Juanjuan; Wang, Ning; Deng, Chao; Zhang, Song; Li, Yue; Chen, Wensheng; Yu, Shiqiang; Yi, Dinghua; Jin, Zhenxiao

    2013-12-01

    Ischemia reperfusion (IR) injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Silent information regulator 1 (SIRT1), a type of histone deacetylase, contributes to IRI. Curcumin (Cur) is a strong natural antioxidant and is the active component in Curcuma longa; Cur has protective effects against IRI and may regulate the activity of SIRT1. This study was designed to investigate the protective effect of Cur pretreatment on myocardial IRI and to elucidate this potential mechanism. Isolated and in vivo rat hearts and cultured neonatal rat cardiomyocytes were subjected to IR. Prior to this procedure, the hearts or cardiomyocytes were exposed to Cur in the absence or presence of the SIRT1 inhibitor sirtinol or SIRT1 siRNA. Cur conferred a cardioprotective effect, as shown by improved postischemic cardiac function, decreased myocardial infarct size, decreased myocardial apoptotic index, and several biochemical parameters, including the up-regulation of the antiapoptotic protein Bcl2 and the down-regulation of the proapoptotic protein Bax. Sirtinol and SIRT1 siRNA each blocked the Cur-mediated cardioprotection by inhibiting SIRT1 signaling. Cur also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase activity, and decreased formation of mitochondrial hydrogen peroxide and malondialdehyde. These observations indicated that the IR-induced mitochondrial oxidative damage was remarkably attenuated. However, this Cur-elevated mitochondrial function was reversed by sirtinol or SIRT1 siRNA treatment. In summary, our results demonstrate that Cur pretreatment attenuates IRI by reducing IR-induced mitochondrial oxidative damage through the activation of SIRT1 signaling.

  8. The nuclear melatonin receptor RORα is a novel endogenous defender against myocardial ischemia/reperfusion injury.

    PubMed

    He, Ben; Zhao, Yichao; Xu, Longwei; Gao, Lingchen; Su, Yuanyuan; Lin, Nan; Pu, Jun

    2016-04-01

    Circadian rhythm disruption or decrease in levels of circadian hormones such as melatonin increases ischemic heart disease risk. The nuclear melatonin receptors RORs are pivotally involved in circadian rhythm regulation and melatonin effects mediation. However, the functional roles of RORs in the heart have never been investigated and were therefore the subject of this study on myocardial ischemia/reperfusion (MI/R) injury pathogenesis. RORα and RORγ subtypes were detected in the adult mouse heart, and RORα but not RORγ was downregulated after MI/R. To determine the pathological consequence of MI/R-induced reduction of RORα, we subjected RORα-deficient staggerer mice and wild-type (WT) littermates to MI/R injury, resulting in significantly increased myocardial infarct size, myocardial apoptosis and exacerbated contractile dysfunction in the former. Mechanistically, RORα deficiency promoted MI/R-induced endoplasmic reticulum stress, mitochondrial impairments, and autophagy dysfunction. Moreover, RORα deficiency augmented MI/R-induced oxidative/nitrative stress. Given the emerging evidence of RORα as an essential melatonin effects mediator, we further investigated the RORα roles in melatonin-exerted cardioprotection, in particular against MI/R injury, which was significantly attenuated in RORα-deficient mice, but negligibly affected by cardiac-specific silencing of RORγ. Finally, to determine cell type-specific effects of RORα, we generated mice with cardiomyocyte-specific RORα overexpression and they were less vulnerable to MI/R injury. In summary, our study provides the first direct evidence that the nuclear melatonin receptor RORα is a novel endogenous protective receptor against MI/R injury and an important mediator of melatonin-exerted cardioprotection; melatonin-RORα axis signaling thus appears important in protection against ischemic heart injury. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Conditional deletion of cardiomyocyte peroxisome proliferator-activated receptor γ enhances myocardial ischemia-reperfusion injury in mice.

    PubMed

    Hobson, Michael J; Hake, Paul W; O'Connor, Michael; Schulte, Christine; Moore, Victoria; James, Jeanne M; Piraino, Giovanna; Zingarelli, Basilia

    2014-01-01

    The nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of the inflammatory response to an array of biologic insults. We have previously demonstrated that PPARγ ligands reduce myocardial ischemia-reperfusion injury in rodents. In the current study, we directly determined the role of cardiomyocyte PPARγ in ischemia-reperfusion injury, using a model of conditional cardiomyocyte-specific deletion of PPARγ in vivo. In mice, α-myosin heavy chain-restricted Cre-mediated PPARγ deficiency was induced by tamoxifen treatment (30 mg/kg intraperitoneally) for 4 days (PPARγ mice), whereas controls included mice treated with the oil diluent vehicle (PPARγ mice). Western blot and histochemical analyses confirmed that expression of PPARγ protein was abolished in cardiomyocytes of mice treated with tamoxifen, but not with vehicle. After tamoxifen or vehicle treatment, animals were subjected to 30-min ligation of the left anterior descending coronary artery followed by 2-h reperfusion. In PPARγ mice, myocardial ischemia and reperfusion induced extensive myocardial damage, which was associated with elevated tissue activity of myeloperoxidase, indicating infiltration of neutrophils, and elevated plasma levels of troponin I when compared with PPARγ mice. Upon echocardiographic analysis, PPARγ mice also demonstrated ventricular dilatation and systolic dysfunction. Plasma levels of the proinflammatory cytokines interleukin 1β and interleukin 6 were higher in PPARγ mice when compared with PPARγ mice. These pathological events in PPARγ mice were associated with enhanced nuclear factor κB DNA binding in the infarcted hearts. Thus, our data suggest that cardiomyocyte PPARγ is a crucial protective receptor and may prevent reperfusion injury by modulating mechanisms of inflammation.

  10. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

    PubMed Central

    2010-01-01

    Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability. PMID:20875134

  11. Cardiac Microvascular Barrier Function Mediates the Protection of Tongxinluo against Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Qi, Kang; Li, Lujin; Li, Xiangdong; Zhao, Jinglin; Wang, Yang; You, Shijie; Hu, Fenghuan; Zhang, Haitao; Cheng, Yutong; Kang, Sheng; Cui, Hehe; Duan, Lian; Jin, Chen; Zheng, Qingshan; Yang, Yuejin

    2015-01-01

    Objective Tongxinluo (TXL) has been shown to decrease myocardial necrosis after ischemia/reperfusion (I/R) by simulating ischemia preconditioning (IPC). However, the core mechanism of TXL remains unclear. This study was designed to investigate the key targets of TXL against I/R injury (IRI) among the cardiac structure-function network. Materials and Methods To evaluate the severity of lethal IRI, a mathematical model was established according to the relationship between myocardial no-reflow size and necrosis size. A total of 168 mini-swine were employed in myocardial I/R experiment. IRI severity among different interventions was compared and IPC and CCB groups were identified as the mildest and severest groups, respectively. Principal component analysis was applied to further determine 9 key targets of IPC in cardioprotection. Then, the key targets of TXL in cardioprotection were confirmed. Results Necrosis size and no-reflow size fit well with the Sigmoid Emax model. Necrosis reduction space (NRS) positively correlates with I/R injury severity and necrosis size (R2=0.92, R2=0.57, P<0.01, respectively). Functional and structural indices correlate positively with NRS (R2=0.64, R2=0.62, P<0.01, respectively). TXL recovers SUR2, iNOS activity, eNOS activity, VE-cadherin, β-catenin, γ-catenin and P-selectin with a trend toward the sham group. Moreover, TXL increases PKA activity and eNOS expression with a trend away from the sham group. Among the above nine indices, eNOS activity, eNOS, VE-cadherin, β-catenin and γ-catenin expression were significantly up-regulated by TXL compared with IPC (P>0.05) or CCB (P<0.05) and these five microvascular barrier-related indices may be the key targets of TXL in minimizing IRI. Conclusions Our study underlines the lethal IRI as one of the causes of myocardial necrosis. Pretreatment with TXL ameliorates myocardial IRI through promoting cardiac microvascular endothelial barrier function by simulating IPC. PMID:25781461

  12. Pharmacodynamic interaction of green tea extract with hydrochlorothiazide against ischemia-reperfusion injury-induced myocardial infarction.

    PubMed

    Chakraborty, Manodeep; Kamath, Jagadish Vasudev

    2014-07-01

    Globally, the rate of development of myocardial diseases and hypertension is very common, which is responsible for incremental morbidity and mortality statistics. Treatment of ischemic hypertensive patients with diuretics such as hydrochlorothiazide (HCTZ) can precipitate myocardial infarction due to hypokalemia. This study was undertaken to evaluate the pharmacodynamic interaction of green tea extract (GTE) with HCTZ against ischemia-reperfusion induced myocardial toxicity. Wistar albino rats of either sex were taken and pretreated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of GTE for 30 days. Standard, high and low dose of interactive groups received HCTZ (10 mg/kg, p.o.) for last 7 days. Ischemia-reperfusion injury was induced by modified Lagendorff apparatus, and the effect of different treatments was evaluated by percentage recovery in terms of heart rate and developed tension, serum biomarkers, and heart tissue antioxidant levels. Prophylactic treatment groups, such as high and low dose of GTE and their interactive groups with HCTZ, exhibited significant percentage recovery in terms of heart rate and developed tension. Apart from that, significant increase in superoxide dismutase and catalase, decrease in thiobarbituric acid reactive species in heart tissue, as well as significant decrease in serum lactate dehydrogenase, creatinine phosphokinase-MB and N-acetylcysteine levels have also been documented. The present findings clearly suggest that GTE dose-dependently reduces myocardial toxicity due to ischemia, and combination with HCTZ can reduce the associated side-effects and exhibits myocardial protection.

  13. Cardioprotective effect of the Hibiscus rosa sinensis flowers in an oxidative stress model of myocardial ischemic reperfusion injury in rat

    PubMed Central

    Gauthaman, Karunakaran K; Saleem, Mohamed TS; Thanislas, Peter T; Prabhu, Vinoth V; Krishnamoorthy, Karthikeyan K; Devaraj, Niranjali S; Somasundaram, Jayaprakash S

    2006-01-01

    Background The present study investigates the cardioprotective effects of Hibiscus rosa sinensis in myocardial ischemic reperfusion injury, particularly in terms of its antioxidant effects. Methods The medicinal values of the flowers of Hibiscus rosa sinensis (Chinese rose) have been mentioned in ancient literature as useful in disorders of the heart. Dried pulverized flower of Hibiscus rosa sinensis was administered orally to Wistar albino rats (150–200 gms) in three different doses [125, 250 and 500 mg/kg in 2% carboxy methyl cellulose (CMC)], 6 days per week for 4 weeks. Thereafter, rats were sacrificed; either for the determination of baseline changes in cardiac endogenous antioxidants [superoxide dismutase, reduced glutathione and catalase] or the hearts were subjected to isoproterenol induced myocardial necrosis. Results There was significant increase in the baseline contents of thiobarbituric acid reactive substances (TBARS) [a measure of lipid per oxidation] with both doses of Hibiscus Rosa sinensis. In the 250 mg/kg treated group, there was significant increase in superoxide dismutase, reduced glutathione, and catalase levels but not in the 125 and 500 mg/kg treated groups. Significant rise in myocardial thiobarbituric acid reactive substances and loss of superoxide dismutase, catalase and reduced glutathione (suggestive of increased oxidative stress) occurred in the vehicle treated hearts subjected to in vivo myocardial ischemic reperfusion injury. Conclusion It may be concluded that flower of Hibiscus rosa sinensis (250 mg/kg) augments endogenous antioxidant compounds of rat heart and also prevents the myocardium from isoproterenol induced myocardial injury. PMID:16987414

  14. Combined morphine and limb remote ischemic perconditioning provides an enhanced protection against myocardial ischemia/reperfusion injury by antiapoptosis.

    PubMed

    Wang, Shi-Yu; Cui, Xin-Long; Xue, Fu-Shan; Duan, Ran; Li, Rui-Ping; Liu, Gao-Pu; Yang, Gui-Zhen; Sun, Chao

    2016-05-01

    Both morphine and limb remote ischemic perconditioning (RIPer) can protect against myocardial ischemia/reperfusion injury (IRI). This experiment was designed to assess whether combined morphine and limb RIPer could provide and enhanced protection against myocardial IRI in an in vivo rat model. One hundred male Sprague-Dawley rats were randomly allocated to six groups: sham, ischemia/reperfusion (IR), ischemic preconditioning, RIPer, morphine (M), and combined morphine and remote ischemic perconditioning (M + RIPer). Ventricular arrhythmias that occurred during ischemia and early reperfusion were scored, and serum creatine kinase isoenzyme and cardiac troponin I levels were assayed. The infarct size was determined by Evans blue and triphenyl tetrazolium chloride staining. The apoptosis in the myocardial ischemic core, ischemic border, and nonischemic areas was assessed through real-time polymerase chain reaction for Bax and Bcl-2 and with the transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay. The infarct size, serum cardiac troponin I level, incidence, and score of the arrhythmias during the initial reperfusion were significantly reduced in the M + RIPer group compared with the IR group but did not differ significantly between the ischemic preconditioning and M + RIPer groups. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling-positive cells were significantly decreased, and the Bcl-2/Bax ratio was significantly increased in the M + RIPer group compared with the IR group. This experiment demonstrates that combined morphine and limb RIPer provides an enhanced protection against myocardial IRI by the Bcl-2-linked apoptotic signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Hearts deficient in both Mfn1 and Mfn2 are protected against acute myocardial infarction

    PubMed Central

    Hall, A R; Burke, N; Dongworth, R K; Kalkhoran, S B; Dyson, A; Vicencio, J M; Dorn II, G W; Yellon, D M; Hausenloy, D J

    2016-01-01

    Mitochondria alter their shape by undergoing cycles of fusion and fission. Changes in mitochondrial morphology impact on the cellular response to stress, and their interactions with other organelles such as the sarcoplasmic reticulum (SR). Inhibiting mitochondrial fission can protect the heart against acute ischemia/reperfusion (I/R) injury. However, the role of the mitochondrial fusion proteins, Mfn1 and Mfn2, in the response of the adult heart to acute I/R injury is not clear, and is investigated in this study. To determine the effect of combined Mfn1/Mfn2 ablation on the susceptibility to acute myocardial I/R injury, cardiac-specific ablation of both Mfn1 and Mfn2 (DKO) was initiated in mice aged 4–6 weeks, leading to knockout of both these proteins in 8–10-week-old animals. This resulted in fragmented mitochondria (electron microscopy), decreased mitochondrial respiratory function (respirometry), and impaired myocardial contractile function (echocardiography). In DKO mice subjected to in vivo regional myocardial ischemia (30 min) followed by 24 h reperfusion, myocardial infarct size (IS, expressed as a % of the area-at-risk) was reduced by 46% compared with wild-type (WT) hearts. In addition, mitochondria from DKO animals had decreased MPTP opening susceptibility (assessed by Ca2+-induced mitochondrial swelling), compared with WT hearts. Mfn2 is a key mediator of mitochondrial/SR tethering, and accordingly, the loss of Mfn2 in DKO hearts reduced the number of interactions measured between these organelles (quantified by proximal ligation assay), attenuated mitochondrial calcium overload (Rhod2 confocal microscopy), and decreased reactive oxygen species production (DCF confocal microscopy) in response to acute I/R injury. No differences in isolated mitochondrial ROS emissions (Amplex Red) were detected in response to Ca2+ and Antimycin A, further implicating disruption of mitochondria/SR tethering as the protective mechanism. In summary, despite apparent

  16. Upregulation of microRNA-22 contributes to myocardial ischemia-reperfusion injury by interfering with the mitochondrial function.

    PubMed

    Du, Jian-Kui; Cong, Bin-Hai; Yu, Qing; Wang, He; Wang, Long; Wang, Chang-Nan; Tang, Xiao-Lu; Lu, Jian-Qiang; Zhu, Xiao-Yan; Ni, Xin

    2016-07-01

    Mitochondrial oxidative damage is critically involved in cardiac ischemia reperfusion (I/R) injury. MicroRNA-22 (miR-22) has been predicted to potentially target sirtuin-1 (Sirt1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), both of which are known to provide protection against mitochondrial oxidative injury. The present study aims to investigate whether miR-22 is involved in the regulation of cardiac I/R injury by regulation of mitochondrial function. We found that miR-22 level was significantly increased in rat hearts subjected to I/R injury, as compared with the sham group. Intra-myocardial injection of 20 ug miR-22 inhibitor reduced I/R injury as evidenced by significant decreases in cardiac infarct size, serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels and the number of apoptotic cardiomyocytes. H9c2 cardiomyocytes exposed to hypoxia/reoxygenation (H/R) insult exhibited an increase in miR-22 expression, which was blocked by reactive oxygen species (ROS) scavenger and p53 inhibitor. In addition, miR-22 inhibitor attenuated, whereas miR-22 mimic aggravated H/R-induced injury in H9c2 cardiomyocytes. MiR-22 inhibitor per se had no significant effect on cardiac mitochondrial function. Mitochondria from rat receiving miR-22 inhibitor 48h before ischemia were found to have a significantly less mitochondrial superoxide production and greater mitochondrial membrane potential and ATP production as compared with rat receiving miR control. In H9c2 cardiomyocyte, it was found that miR-22 mimic aggravated, whilst miR-22 inhibitor significantly attenuated H/R-induced mitochondrial damage. By using real time PCR, western blot and dual-luciferase reporter gene analyses, we identified Sirt1 and PGC1α as miR-22 targets in cardiomyocytes. It was found that silencing of Sirt1 abolished the protective effect of miR-22 inhibitor against H/R-induced mitochondrial dysfunction and cell injury in cardiomyocytes. Taken together, our

  17. Acute posteroinferior wall myocardial infarction secondary to football chest trauma.

    PubMed

    Espinosa, R; Badui, E; Castaño, R; Madrid, R

    1985-12-01

    Myocardial infarction secondary to nonpenetrating chest trauma is rare. We present the case of a sportsman who developed an acute transmural posteroinferior wall myocardial infarction due to chest trauma by a football. The angiographic study revealed total obstruction of the proximal right coronary artery.

  18. Acute myocardial infarction in a young woman on isotretinoin treatment.

    PubMed

    Lorenzo, Natalia; Antuña, Paula; Dominguez, Lourdes; Rivero, Fernando; Bastante, Teresa; Alfonso, Fernando

    2015-02-15

    The use of isotretinoin has been associated with mild changes in the metabolic profile of adolescents. In very rare cases, a possible association with myocardial infarction, stroke and thromboembolic events has been reported. In this report we describe the potential association of isotretinoin with the occurrence of an acute myocardial infarction in a very young girl. OCT provided unique visualization of the culprit lesion.

  19. Protease-Activated Receptor 4 Deficiency Offers Cardioprotection after Acute Ischemia Reperfusion Injury

    PubMed Central

    Kolpakov, Mikhail A.; Rafiq, Khadija; Guo, Xinji; Hooshdaran, Bahman; Wang, Tao; Vlasenko, Liudmila; Bashkirova, Yulia V.; Zhang, Xiaoxiao; Chen, Xiongwen; Iftikhar, Sahar; Libonati, Joseph R.; Kunapuli, Satya P.; Sabri, Abdelkarim

    2016-01-01

    Protease-activated receptor (PAR)4 is a low affinity thrombin receptor with less understood function relative to PAR1. PAR4 is involved in platelet activation and hemostasis, but its specific actions on myocyte growth and cardiac function remain unknown. This study examined the role of PAR4 deficiency on cardioprotection after myocardial ischemia-reperfusion (IR) injury in mice. When challenged by in vivo or ex vivo IR, PAR4 knockout (KO) mice exhibited increased tolerance to injury, which was manifest as reduced infarct size and a more robust functional recovery compared to wild-type mice. PAR4 KO mice also showed reduced cardiomyocyte apoptosis and putative signaling shifts in survival pathways in response to IR. Inhibition of PAR4 expression in isolated cardiomyocytes by shRNA offered protection against thrombin and PAR4-agonist peptide-induced apoptosis, while overexpression of wild-type PAR4 significantly enhanced the susceptibility of cardiomyocytes to apoptosis, even under low thrombin concentrations. Further studies implicate Src- and epidermal growth factor receptor-dependent activation of JNK on the proapoptotic effect of PAR4 in cardiomyocytes. These findings reveal a pivotal role for PAR4 as a regulator of cardiomyocyte survival and point to PAR4 inhibition as a therapeutic target offering cardioprotection after acute IR injury. PMID:26643815

  20. Short- and long-term effects of (-)-epicatechin on myocardial ischemia-reperfusion injury.

    PubMed

    Yamazaki, Katrina Go; Romero-Perez, Diego; Barraza-Hidalgo, Maraliz; Cruz, Michelle; Rivas, Maria; Cortez-Gomez, Brenda; Ceballos, Guillermo; Villarreal, Francisco

    2008-08-01

    Epidemiological studies have shown a correlation between flavonoid-rich diets and improved cardiovascular prognosis. Cocoa contains large amounts of flavonoids, in particular flavanols (mostly catechins and epicatechins). Flavonoids possess pleiotropic properties that may confer protective effects to tissues during injury. We examined the ability of epicatechin to reduce short-and long-term ischemia-reperfusion (I/R) myocardial injury. Epicatechin (1 mg.kg(-1).day(-1)) pretreatment (Tx) was administered daily via oral gavage to male rats for 2 or 10 days. Controls received water. Ischemia was induced via a 45-min coronary occlusion. Reperfusion was allowed until 48 h or 3 wk while Tx continued. We measured infarct (MI) size (%), hemodynamics, myeloperoxidase activity, tissue oxidative stress, and matrix metalloproteinase-9 (MMP-9) activity in 48-h groups. Cardiac morphometry was also evaluated in 3-wk groups. With 2 days of Tx, no reductions in MI size occurred. After 10 days, a significant approximately 50% reduction in MI size occurred. Epicatechin rats demonstrated no significant changes in hemodynamics. Tissue oxidative stress was reduced significantly in the epicatechin group vs. controls. MMP-9 activity demonstrated limited increases in the infarct region with epicatechin. By 3 wk, a significant 32% reduction in infarct size was observed with Tx, accompanied with sustained hemodynamics and preserved chamber morphometry. In conclusion, epicatechin Tx confers cardioprotection in the setting of I/R injury. The effects are independent of changes in hemodynamics, are sustained over time, and are accompanied by reduced levels of indicators of tissue injury. Results warrant the evaluation of cocoa flavanols as possible therapeutic agents to limit ischemic injury.

  1. Short- and long-term effects of (−)-epicatechin on myocardial ischemia-reperfusion injury

    PubMed Central

    Yamazaki, Katrina Go; Romero-Perez, Diego; Barraza-Hidalgo, Maraliz; Cruz, Michelle; Rivas, Maria; Cortez-Gomez, Brenda; Ceballos, Guillermo; Villarreal, Francisco

    2008-01-01

    Epidemiological studies have shown a correlation between flavonoid-rich diets and improved cardiovascular prognosis. Cocoa contains large amounts of flavonoids, in particular flavanols (mostly catechins and epicatechins). Flavonoids possess pleiotropic properties that may confer protective effects to tissues during injury. We examined the ability of epicatechin to reduce short-and long-term ischemia-reperfusion (I/R) myocardial injury. Epicatechin (1 mg·kg−1·day−1) pretreatment (Tx) was administered daily via oral gavage to male rats for 2 or 10 days. Controls received water. Ischemia was induced via a 45-min coronary occlusion. Reperfusion was allowed until 48 h or 3 wk while Tx continued. We measured infarct (MI) size (%), hemodynamics, myeloperoxidase activity, tissue oxidative stress, and matrix metalloproteinase-9 (MMP-9) activity in 48-h groups. Cardiac morphometry was also evaluated in 3-wk groups. With 2 days of Tx, no reductions in MI size occurred. After 10 days, a significant ∼50% reduction in MI size occurred. Epicatechin rats demonstrated no significant changes in hemodynamics. Tissue oxidative stress was reduced significantly in the epicatechin group vs. controls. MMP-9 activity demonstrated limited increases in the infarct region with epicatechin. By 3 wk, a significant 32% reduction in infarct size was observed with Tx, accompanied with sustained hemodynamics and preserved chamber morphometry. In conclusion, epicatechin Tx confers cardioprotection in the setting of I/R injury. The effects are independent of changes in hemodynamics, are sustained over time, and are accompanied by reduced levels of indicators of tissue injury. Results warrant the evaluation of cocoa flavanols as possible therapeutic agents to limit ischemic injury. PMID:18567705

  2. After Myocardial Ischemia-Reperfusion, miR-29a, and Let7 Could Affect Apoptosis through Regulating IGF-1

    PubMed Central

    Wang, Lei; Niu, Xuehong; Hu, Jihua; Xing, Haijian; Sun, Min; Wang, Juanli; Jian, Qiang; Yang, Hua

    2015-01-01

    Cardiovascular and cerebrovascular ischemic disease is a large class of diseases that is harmful to human health. The primary treatment for the ischemic disease is to recover the blood perfusion and relieve the tissue hypoxia and the shortage of the nutrients in the supply of nutrients. In recent years, investigations found that IGF-1 has a protective effect on cardiovascular disease, especially in myocardial ischemia-reperfusion injury. Investigation into molecular mechanism of ischemia-reperfusion injury may offer potential targets for the development of novel diagnostic strategies. In this study we defined IGF-1 was differentially expressed in the I/R model of the Mus musculus and IGF-1 was the target gene of miR-29a and Let7f. After ischemia-reperfusion, the expression of miR-29a and Let7f increased, while the expression of IGF-1 decreased significantly in the animal model assay. Further studies have found that IGF-1 could inhibit cell apoptosis signaling pathway, thus protecting the reperfusion injury. These results provide new understanding of ischemia-reperfusion injury, with the hope of offering theoretical support for future therapeutic studies. PMID:26844226

  3. Pyrroloquinoline quinone (PQQ) decreases myocardial infarct size and improves cardiac function in rat models of ischemia and ischemia/reperfusion.

    PubMed

    Zhu, Bo-Qing; Zhou, Hui-Zhong; Teerlink, John R; Karliner, Joel S

    2004-11-01

    As pyrroloquinoline quinone (PQQ) is a redox cofactor in mammals, we asked if it is cardioprotective. Rats were subjected to 2 h of left anterior descending (LAD) coronary artery ligation without reperfusion (model 1, ischemia). In model 2 (ischemia/reperfusion), rats were subjected to 17 or 30 min of LAD occlusion and 2 h of reperfusion. PQQ (15-20 mg/kg) was given i.p., either 30 min before LAD occlusion (Pretreatment) or i.v. at the onset of reperfusion (Treatment). In model 1, PQQ reduced infarct size (10.0 +/- 1.5 vs 19.1 +/- 2.1%, P < 0.01). In model 2, either PQQ Pretreatment or Treatment also reduced infarct size (18.4 +/- 2.3 and 25.6 +/- 3.5% vs 38.1 +/- 2.6%, P < 0.01). PQQ resulted in higher LV developed pressure and LV (+)dP/dt after 1-2 h of reperfusion (P < 0.05), and fewer ventricular fibrillation episodes. PQQ dose (5-20 mg/kg) was inversely related to infarct size. PQQ reduced myocardial tissue levels of malondialdehyde (MDA), an indicator of lipid peroxidation (316 +/- 88 vs 99 +/- 14 nmol/g, P < 0.01). PQQ given either as Pretreatment or as Treatment at the onset of reperfusion is highly effective in reducing infarct size and improving cardiac function in a dose-related manner in rat models of ischemia and ischemia/reperfusion. The optimal dose in this study, which exhibited neither renal nor hepatic toxicity, was 15 mg/kg, but lower doses may also be efficacious. We conclude that PQQ, which appears to act as a free radical scavenger in ischemic myocardium, is a highly effective cardioprotective agent.

  4. Mild type 2 diabetes mellitus improves remote endothelial dysfunction after acute myocardial infarction.

    PubMed

    Korkmaz-Icöz, Sevil; Vater, Adrian; Li, Shiliang; Lehner, Alice; Radovits, Tamás; Hegedűs, Péter; Ruppert, Mihály; Brlecic, Paige; Zorn, Markus; Karck, Matthias; Szabó, Gábor

    2015-01-01

    Myocardial infarction (MI) is a common cause of mortality in patients with diabetes mellitus (DM) and vascular dysfunction is a major component of diabetic cardiomyopathy. We investigated the systemic influence of acute MI on the diabetes-induced pathogenic changes in the rat aorta. Nondiabetic Wistar (W) and type-2 diabetic Goto-Kakizaki (GK) rats underwent 45min of left anterior descending coronary artery occlusion followed by 24h of reperfusion. Isometric force was measured using organ bath. Plasma glucose-levels were significantly higher in diabetic rats (GK+sham: 13±2mM; GK+MI: 19±2mM) compared to nondiabetic rats (W+sham: 8±0mM; W+MI: 8±1mM). Acetylcholine-induced relaxation was significantly weaker in rings from W+MI and GK+MI rats compared to corresponding sham-operated animals. Myocardial reperfusion injury was smaller in GK+MI than W+MI rats, and the concentration-response curves to acetylcholine were significantly enhanced in rings from GK+MI than W+MI rats. Nevertheless, the relaxation response to acetylcholine was similar in W+sham and GK+sham. Densitometric analysis of bands for endothelial nitric oxide synthase showed a significant decrease in W+MI rats compared to W+sham and GK+sham animals. Aortas from both GK+sham and GK+MI rats showed impaired contractile responses to phenylephrine in comparison with the nondiabetics. For the first time we showed that short-term and mild type-2 DM improved remote endothelial dysfunction after reperfused acute MI. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. An Unusual Complication Following Transarterial Chemoembolization: Acute Myocardial Infarction

    SciTech Connect

    Lai Yiliang; Chang Weichou; Kuo Wuhsien; Huang Tienyu; Chu Hengcheng; Hsieh Tsaiyuan; Chang Weikuo

    2010-02-15

    Transarterial chemoembolization has been widely used to treat unresectable hepatocellular carcinoma. Various complications have been reported, but they have not included acute myocardial infarction. Acute myocardial infarction results mainly from coronary artery occlusion by plaques that are vulnerable to rupture or from coronary spasm, embolization, or dissection of the coronary artery. It is associated with significant morbidity and mortality. We present a case report that describes a patient with hepatocellular carcinoma who underwent transarterial chemoembolization and died subsequently of acute myocardial infarction. To our knowledge, there has been no previous report of this complication induced by transarterial chemoembolization for hepatocellular carcinoma. This case illustrates the need to be aware of acute myocardial infarction when transarterial chemoembolization is planned for the treatment of hepatocellular carcinoma, especially in patients with underlying coronary artery disease.

  6. Acute myocardial infarction and sudden death in Sioux Indians.

    PubMed

    Hrabovsky, S L; Welty, T K; Coulehan, J L

    1989-04-01

    While some Indian tribes have low rates of acute myocardial infarction, Northern Plains Indians, including the Sioux, have rates of morbidity and mortality from acute myocardial infarction higher than those reported for the United States population in general. In a review of diagnosed cases of acute myocardial infarction over a 3-year period in 2 hospitals serving predominantly Sioux Indians, 8% of cases were found misclassified, and 22% failed to meet rigorous diagnostic criteria, although the patients did indeed have ischemic heart disease. Patients had high frequencies of complications and risk factors and a fatality rate of 16% within a month of admission. Sudden deaths likely due to ischemic heart disease but in persons not diagnosed as having acute myocardial infarction by chart review occurred 3 times more frequently than deaths occurring within a month of clinical diagnosis.

  7. Pretreatment with low doses of acenocoumarol inhibits the development of acute ischemia/reperfusion-induced pancreatitis.

    PubMed

    Warzecha, Z; Sendur, P; Ceranowicz, P; Dembinski, M; Cieszkowski, J; Kusnierz-Cabala, B; Tomaszewska, R; Dembinski, A

    2015-10-01

    Coagulative disorders are known to occur in acute pancreatitis and are related to the severity of this disease. Various experimental and clinical studies have shown protective and therapeutic effect of heparin in acute pancreatitis. Aim of the present study was to determine the influence of acenocoumarol, a vitamin K antagonist, on the development of acute pancreatitis. Studies were performed on male Wistar rats weighing 250 - 270 g. Acenocoumarol at the dose of 50, 100 or 150 μg/kg/dose or vehicle were administered once a day for 7 days before induction of acute pancreatitis. Acute pancreatitis was induced in rats by pancreatic ischemia followed by reperfusion. The severity of acute pancreatitis was assessed after 5-h reperfusion. Pretreatment with acenocoumarol given at the dose of 50 or 100 μg/kg/dose reduced morphological signs of acute pancreatitis. These effects were accompanied with a decrease in the pancreatitis-evoked increase in serum activity of lipase and serum concentration of pro-inflammatory interleukin-1β. Moreover, the pancreatitis-evoked reductions in pancreatic DNA synthesis and pancreatic blood flow were partially reversed by pretreatment with acenocoumarol given at the dose of 50 and 100 μg/kg/dose. Administration of acenocoumarol at the dose of 150 μg/kg/dose did not exhibit any protective effect against ischemia/reperfusion-induced pancreatitis. We concluded that pretreatment with low doses of acenocoumarol reduces the severity of ischemia/reperfusion-induced acute pancreatitis.

  8. Oxygen therapy for acute myocardial infarction.

    PubMed

    Cabello, Juan B; Burls, Amanda; Emparanza, José I; Bayliss, Susan E; Quinn, Tom

    2016-12-19

    Oxygen (O2) is widely used in people with acute myocardial infarction (AMI). Previous systematic reviews concluded that there was insufficient evidence to know whether oxygen reduced, increased or had no effect on heart ischaemia or infarct size. Our first Cochrane review in 2010 also concluded there was insufficient evidence to know whether oxygen should be used. Since 2010, the lack of evidence to support this widely used intervention has attracted considerable attention, prompting further trials of oxygen therapy in myocardial infarction patients. It is thus important to update this Cochrane review. To assess the effects of routine use of inhaled oxygen for acute myocardial infarction (AMI). We searched the following bibliographic databases on 6 June 2015: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (OVID), Embase (OVID), CINAHL (EBSCO) and Web of Science (Thomson Reuters). LILACS (Latin American and Caribbean Health Sciences Literature) was last searched in September 2016. We also contacted experts to identify eligible studies. We applied no language restrictions. Randomised controlled trials in people with suspected or proven AMI (ST-segment elevation myocardial infarction (STEMI) or non-STEMI) within 24 hours after onset, in which the intervention was inhaled oxygen (at normal pressure) compared to air, regardless of co-therapies provided to participants in both arms of the trial. Two authors independently reviewed the titles and abstracts of identified studies to see if they met the inclusion criteria and independently undertook the data extraction. We assessed the quality of studies and the risk of bias according to guidance in the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was death. The measure of effect used was the risk ratio (RR) with a 95% confidence interval (CI). We used the GRADE approach to evaluate the quality of the evidence and the GRADE profiler (GRADEpro) to

  9. Quantifying the Area at Risk in Reperfused ST-Segment-Elevation Myocardial Infarction Patients Using Hybrid Cardiac Positron Emission Tomography-Magnetic Resonance Imaging.

    PubMed

    Bulluck, Heerajnarain; White, Steven K; Fröhlich, Georg M; Casson, Steven G; O'Meara, Celia; Newton, Ayla; Nicholas, Jennifer; Weale, Peter; Wan, Simon M Y; Sirker, Alex; Moon, James C; Yellon, Derek M; Groves, Ashley; Menezes, Leon; Hausenloy, Derek J

    2016-03-01

    Hybrid positron emission tomography and magnetic resonance allows the advantages of magnetic resonance in tissue characterizing the myocardium to be combined with the unique metabolic insights of positron emission tomography. We hypothesized that the area of reduced myocardial glucose uptake would closely match the area at risk delineated by T2 mapping in ST-segment-elevation myocardial infarction patients. Hybrid positron emission tomography and magnetic resonance using (18)F-fluorodeoxyglucose (FDG) for glucose uptake was performed in 21 ST-segment-elevation myocardial infarction patients at a median of 5 days. Follow-up scans were performed in a subset of patients 12 months later. The area of reduced FDG uptake was significantly larger than the infarct size quantified by late gadolinium enhancement (37.2±11.6% versus 22.3±11.7%; P<0.001) and closely matched the area at risk by T2 mapping (37.2±11.6% versus 36.3±12.2%; P=0.10, R=0.98, bias 0.9±4.4%). On the follow-up scans, the area of reduced FDG uptake was significantly smaller in size when compared with the acute scans (19.5 [6.3%-31.8%] versus 44.0 [21.3%-55.3%]; P=0.002) and closely correlated with the areas of late gadolinium enhancement (R 0.98) with a small bias of 2.0±5.6%. An FDG uptake of ≥45% on the acute scans could predict viable myocardium on the follow-up scan. Both transmural extent of late gadolinium enhancement and FDG uptake on the acute scan performed equally well to predict segmental wall motion recovery. Hybrid positron emission tomography and magnetic resonance in the reperfused ST-segment-elevation myocardial infarction patients showed reduced myocardial glucose uptake within the area at risk and closely matched the area at risk delineated by T2 mapping. FDG uptake, as well as transmural extent of late gadolinium enhancement, acutely can identify viable myocardial segments. © 2016 American Heart Association, Inc.

  10. Adora2b Signaling on Bone Marrow Derived Cells Dampens Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Koeppen, Michael; Harter, Patrick N.; Bonney, Stephanie; Bonney, Megan; Reithel, Susan; Zachskorn, Cornelia; Mittelbronn, Michel; Eckle, Tobias

    2012-01-01

    Background Cardiac ischemia-reperfusion injury (I/R) represents a major cause of cardiac tissue injury. Adenosine signaling dampens inflammation during cardiac I/R. Here, we investigated the role of the adenosine A2b-receptor (Adora2b) on inflammatory cells during cardiac I/R. Methods To study Adora2b signaling on inflammatory cells, we transplanted wild-type (WT) bone marrow (BM) into Adora2b−/− mice or Adora2b−/− BM into WT mice. To study the role of polymorphonuclear leukocytes (PMNs), neutrophil-depleted WT mice were treated with an Adora2b agonist. Following treatments, mice were exposed to 60 min of myocardial ischemia and 120 min of reperfusion. Infarct sizes and Troponin-I levels were determined by triphenyltetrazolium chloride staining and ELISA, respectively. Results Transplantation of WT-BM into Adora2b−/− mice decreased infarct sizes by 19 ± 4% and Troponin-I by 87.5 ± 25.3 ng/ml (mean ± SD, n = 6). Transplantation of Adora2b−/− BM into WT mice increased infarct sizes by 20 ±3% and Troponin-I levels by 69.7 ± 17.9 ng/ml (mean ± SD, n = 6). Studies on the reperfused myocardium revealed PMNs as dominant cell type. PMN-depletion or Adora2b agonist treatment reduced infarct sizes by 30 ± 11% or 26 ± 13% (mean ± SD, n = 4), however the combination of both did not reveal further cardioprotection. Cytokine profiling showed significantly higher cardiac tumor-necrosis-factor-α levels in Adora2b−/− compared to WT mice (39.3 ± 5.3 vs. 7.5 ± 1.0 pg/mg protein, mean ± SD, n = 4). Pharmacological studies on human activated PMNs revealed an Adora2b dependent tumor-necrosis-factor-α release. Conclusion Adora2b signaling on BM-derived cells such as PMNs represents an endogenous cardioprotective mechanism during cardiac I/R. Our findings suggest that Adora2b agonist treatment during cardiac I/R reduces tumor-necrosis-factor-α release of PMNs, thereby dampening tissue injury. PMID:22531331

  11. Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

    SciTech Connect

    Li, Weixin; Wu, Mingchai; Tang, Longguang; Pan, Yong; Liu, Zhiguo; Zeng, Chunlai; Wang, Jingying; Wei, Tiemin; Liang, Guang

    2015-01-15

    Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia/reperfusion

  12. Iodide Protects Heart Tissue from Reperfusion Injury

    PubMed Central

    Iwata, Akiko; Morrison, Michael L.; Roth, Mark B.

    2014-01-01

    Iodine is an elemental nutrient that is essential for mammals. Here we provide evidence for an acute therapeutic role for iodine in ischemia reperfusion injury. Infusion of the reduced form, iodide, but not the oxidized form iodate, reduces heart damage by as much as 75% when delivered intravenously following temporary loss of blood flow but prior to reperfusion of the heart in a mouse model of acute myocardial infarction. Normal thyroid function may be required because loss of thyroid activity abrogates the iodide benefit. Given the high degree of protection and the high degree of safety, iodide should be explored further as a therapy for reperfusion injury. PMID:25379708

  13. Protection of Distal Embolization in High-Risk Patients with Acute ST-Segment Elevation Myocardial Infarction (PREMIAR).

    PubMed

    Cura, Fernando A; Escudero, Alejandro Garcia; Berrocal, Daniel; Mendiz, Oscar; Trivi, Marcelo S; Fernandez, Juan; Palacios, Alejandro; Albertal, Mariano; Piraino, Ruben; Riccitelli, Miguel Angel; Gruberg, Luis; Ballarino, Miguel; Milei, Jose; Baeza, Ricardo; Thierer, Jorge; Grinfeld, Liliana; Krucoff, Mitchell; O'Neill, William; Belardi, Jorge

    2007-02-01

    Distal embolization may decrease myocardial reperfusion after primary percutaneous coronary intervention (PCI). Nonetheless, results of previous trials assessing the role of distal protection during primary PCI have been controversial. The Protection of Distal Embolization in High-Risk Patients with Acute ST-Segment Elevation Myocardial Infarction Trial (PREMIAR) was a prospective, randomized, controlled study designed to evaluate the role of filter-based distal protection during PCI in patients with acute ST-segment elevation myocardial infarction at high risk of embolic events (including only baseline Thrombolysis In Myocardial Infarction grade 0 to 2 flow). The primary end point was continuous monitoring of ST-segment resolution. Secondary end points included core laboratory analysis of angiographic myocardial blush, ejection fraction measured by cardiac ultrasound, and adverse cardiac events at 6 months. From a total of 194 enrolled patients, 140 subjects were randomized to PCI with or without embolic protection, and 54 were included in a registry arm due to the presence of angiographic exclusion criteria. Baseline characteristics were comparable between arms. The rate of complete ST-segment resolution (>or=70%) at 60 minutes was similar in patients treated with or without distal protection (61.2% vs 60.3%, respectively, p = 0.85). Angiographic myocardial blush (67% vs 70.7%, p = 0.73), in-hospital ejection fraction (47.4 +/- 9.9% vs 45.3 +/- 7.3%, p = 0.29), and combined end point of death, heart failure, or reinfarction at 6 months (14.3% vs 15.7%, p = 0.81) were consistently achieved in a similar proportion in the 2 groups. In conclusion, the use of filter-based distal protection is safe and effectively retrieves debris; however, such use does not translate into an improvement of myocardial reperfusion, left ventricular performance, or clinical outcomes.

  14. Acute microvascular action of vascular endothelial growth factor in skeletal muscle ischemia/reperfusion injury.

    PubMed

    Wang, Wei Z; Fang, Xin-Hua; Stepheson, Linda L; Khiabani, Kayvan T; Zamboni, William A

    2005-04-15

    The purpose of this study was to investigate the acute action of vascular endothelial growth factor (VEGF) in the microcirculation of skeletal muscle subject to ischemia/reperfusion in vivo and to determine the role of nitric oxide synthase in VEGF-induced microvascular protection. A vascular pedicle isolated rat cremaster muscle model coupled with local intraarterial infusion technique was used. Each muscle underwent 4 hours of zero-flow warm ischemia followed by 2 hours of reperfusion. Femoral artery cannulation was performed before reperfusion. The infusate was administered by continuous infusion into the arterial tree of the muscle beginning at 1 minute before reperfusion and at the rate of 0.1 ml/hour throughout the entire reperfusion period. Three groups were designed: (1) the ischemia/reperfusion group, with infusion normal saline; (2) the VEGF plus ische-mia/reperfusion group, with infusion of recombinant human VEGF165 protein; and (3) the L-NA plus VEGF plus ischemia/reperfusion group, with infusion of N-nitro-L-arginine (L-NA; a nonselective nitric oxide synthase antagonist) mixed with VEGF165 protein. After 2 hours of reperfusion, microcirculation measurements including arteriole diameter, capillary perfusion, and endothelium-dependent and endothelium-independent vasodilatation were performed. The muscle was harvested and processed for reverse-transcriptase polymerase chain reaction for measuring eNOS and endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) gene expression. Reperfusion caused significant microvascular alterations including vasoconstriction, poor capillary perfusion, and endothelial dysfunction in the skeletal muscle. These alterations were significantly attenuated by intraarterial infusion of VEGF during reperfusion, but the beneficial effect of VEGF was reduced significantly by coadministration of L-NA. Reverse-transcriptase polymerase chain reaction study revealed that ischemia/reperfusion depressed e

  15. Myocardial and coronary endothelial protective effects of acetylcholine after myocardial ischaemia and reperfusion in rats: role of nitric oxide.

    PubMed Central

    Richard, V.; Blanc, T.; Kaeffer, N.; Tron, C.; Thuillez, C.

    1995-01-01

    1. Recent experiments suggest that acetylcholine (ACh) may exert myocardial protective effects during ischaemia (I) and reperfusion (R). The present study was designed (i) to assess whether ACh limits infarct size and protects coronary endothelial cells in a rat model of I and R, (ii) to evaluate the role of ATP-sensitive potassium (KATP) channels and nitric oxide (NO) in the beneficial effect of ACh (iii) to evaluate whether the protective effect of ACh also extends to coronary endothelial cells and (iv) to assess whether ACh contributes to the beneficial effect of preconditioning. 2. Anaesthetized rats were subjected to 20 min I (left coronary artery occlusion) and 2 h of R. Infarct size was assessed by triphenyltetrazolium (TTC) staining and expressed as a % of the area at risk (India ink injection). Vascular studies were performed on 1.5-2 mm coronary segments (internal diameter 250-300 micros) removed distal to the site of occlusion and mounted in wire myographs. 3. ACh limited infarct size (from 59 +/- 3 to 26 +/- 5%, P < 0.01), and this was prevented by atropine (46 +/- 7%; P < 0.05 vs ACh), but not by the inhibitor of KATP channels, glibenclamide (29 +/- 8%). The inhibitor of NO synthesis NG-nitro L-arginine did not affect infarct size (54 +/- 5%) but abolished the beneficial effect of ACh (59 +/- 8%; P < 0.05 vs ACh), whereas the NO donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1 limited infarct size to the same extent as ACh (28 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8564215

  16. Evaluation of reperfused myocardial infarction by low-dose multidetector computed tomography using prospective electrocardiography (ECG)-triggering: comparison with magnetic resonance imaging.

    PubMed

    Gweon, Hye Mi; Kim, Sang Jin; Kim, Tae Hoon; Lee, Sang Min; Hong, Yoo Jin; Rim, Se-Joong; Hong, Bum Ki; Min, Phil Ki; Yoon, Young Won; Kwon, Hyuck Moon

    2010-09-01

    To evaluate the potential of prospective electrocardiography (ECG)- gated 64-slice multidetector computed tomography (MDCT) for evaluation of myocardial enhancement, infarct size, and stent patency after percutaneous coronary intervention (PCI) with stenting in patients with myocardial infarction. Seventeen patients who were admitted with acute myocardial infarction were examined with prospective ECG-gated 64-slice cardiac MDCT and magnetic resonance (MR) imaging after reperfusion using PCI with stenting. Cardiac MDCT was performed with two different phases: arterial and delayed phases. We evaluated the stent patency on the arterial phase, and nonviable myocardium on the delayed phase of computed tomography (CT) image, and they were compared with the results from the delayed MR images. Total mean radiation dose was 7.7 +/- 0.5 mSv on the two phases of CT images. All patients except one showed good patency of the stent at the culprit lesion on the arterial phase CT images. All patients had hyperenhanced area on the delayed phase CT images, which correlated well with those on the delayed phase MR images, with a mean difference of 1.6% (20 +/- 10% vs. 22 +/- 10%, r = 0.935, p = 0.10). Delayed MR images had a better contrast-to-noise ratio (CNR) than delayed CT images (27.1 +/- 17.8% vs. 4.3 +/- 2.1%, p < 0.001). Prospective ECG-gated 64-slice MDCT provides the potential to evaluate myocardial viability on delayed phase as well as for stent patency on arterial phase with an acceptable radiation dose after PCI with stenting in patients with myocardial infarction.

  17. Radionuclide imaging of myocardial perfusion and viability in assessment of acute myocardial infarction

    SciTech Connect

    Berman, D.S.; Kiat, H.; Maddahi, J.; Shah, P.K.

    1989-07-18

    Technical advances in radionuclide imaging have important implications for the management of patients with acute myocardial infarction. Single-photon emission computerized tomography with thallium 201 (TI-201) offers greater accuracy than planar imaging in detecting, localizing and sizing myocardial perfusion defects. Use of single-photon emission computerized tomography with TI-201 should allow for a more accurate assessment of prognosis after myocardial infarction. A new radiopharmaceutical, technetium 99-m methoxyisobutyl isonitrile, provides a number of advantages over TI-201, including higher quality images, lack of redistribution, and the ability to assess first-pass ventricular function. Applications of TI-201 and technetium 99-m methoxyisobutyl isonitrile include assessment of arterial patency and myocardial salvage immediately after thrombolytic therapy, detection of resting ischemia after thrombolytic therapy, targeting of subsets of patients for further intervention, and predischarge assessment to predict the future course of patients after an acute myocardial infarction.

  18. Acute myocardial infarction and renal failure following naphtha ingestion.

    PubMed

    Roberge, R J; Crippen, D R; Jayadevappa, D; Kosek, T L

    2001-10-01

    We present a case of a non-Q wave myocardial infarction and acute renal failure following an ingestion of naphtha, a petroleum distillate composed primarily of hydrocarbons. The patient's renal, metabolic, and cardiac status improved over several days with aggressive volume replacement and bicarbonate therapy. Acute cardiotoxic effects of hydrocarbon exposure generally manifest as dysrhythmias, secondary to myocardial sensitization to circulating catecholamines, or, possibly, coronary vasospasm. Ischemia from associated hypotension or direct myocardial toxicity are other potential causes of naphtha-related cardiac injury.

  19. Correlation of left ventricular dyssynchrony with myocardial stunning using dual single photon emission computed tomography of (123)iodine-beta-methyl iodophenyl pentadecanoic acid and (201)thallium scintigraphy after reperfusion therapy.

    PubMed

    Maruyama, Yoshiaki; Masaki, Nobuyuki; Shimizu, Yuji; Honda, Norinari; Yoshimoto, Nobuo

    2009-11-01

    Left ventricular (LV) dyssynchrony after reperfusion therapy has been closely examined as a cause of chronic remodeling, but the details have not been clarified. The present study measured LV dyssynchrony appearing immediately after reperfusion therapy using real-time three-dimensional echocardiography (RT-3DE), and assessed the significance of this phenomenon in relation to dual single photon emission computed tomography (SPECT) of (123)iodine beta methyliodophenyl pentadecanoic acid ((123)I-BMIPP) and (201)thallium ((201)Tl). Subjects comprised 58 patients with first-time acute myocardial infarction who received reperfusion therapy and underwent RT-3DE and dual SPECT of (123)I-BMIPP and (201)Tl within two weeks of onset. Two dyssynchrony parameters were measured using RT-3DE in the acute phase and six months later. After evaluating the correlation of these dyssynchrony parameters to resting (201)Tl uptake, (201)Tl washout, (123)I-BMIPP uptake, and (201)Tl-(123)I-BMIPP discrepancy (Tl-BMIPP discrepancy), we compared scintigraphic parameters in the chronic phase between groups with improved dyssynchrony and those without. Acute dyssynchrony exhibited a significant positive correlation to Tl-BMIPP discrepancy and it was significantly increased in the group with improved dyssynchrony in the chronic phase, revealing close relationship between dyssynchrony and Tl-BMIPP discrepancy. Then the subjects were divided into positive Tl-BMIPP discrepancy and negative discrepancy groups, and the parameters of cardiac function were compared between them. In the chronic phase, improved cardiac function was observed in the group with positive Tl-BMIPP discrepancy compared to negative discrepancy. LV dyssynchrony after reperfusion therapy correlates positively with Tl-BMIPP discrepancy, reflecting acute myocardial stunning, in which ventricular contraction improves during the chronic phase.

  20. Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury.

    PubMed

    Durst, Ronen; Danenberg, Haim; Gallily, Ruth; Mechoulam, Raphael; Meir, Keren; Grad, Etty; Beeri, Ronen; Pugatsch, Thea; Tarsish, Elizabet; Lotan, Chaim

    2007-12-01

    Cannabidiol (CBD) is a major, nonpsychoactive Cannabis constituent with anti-inflammatory activity mediated by enhancing adenosine signaling. Inasmuch as adenosine receptors are promising pharmaceutical targets for ischemic heart diseases, we tested the effect of CBD on ischemic rat hearts. For the in vivo studies, the left anterior descending coronary artery was transiently ligated for 30 min, and the rats were treated for 7 days with CBD (5 mg/kg ip) or vehicle. Cardiac function was studied by echocardiography. Infarcts were examined morphometrically and histologically. For ex vivo evaluation, CBD was administered 24 and 1 h before the animals were killed, and hearts were harvested for physiological measurements. In vivo studies showed preservation of shortening fraction in CBD-treated animals: from 48 +/- 8 to 39 +/- 8% and from 44 +/- 5 to 32 +/- 9% in CBD-treated and control rats, respectively (n = 14, P < 0.05). Infarct size was reduced by 66% in CBD-treated animals, despite nearly identical areas at risk (9.6 +/- 3.9 and 28.2 +/- 7.0% in CBD and controls, respectively, P < 0.001) and granulation tissue proportion as assessed qualitatively. Infarcts in CBD-treated animals were associated with reduced myocardial inflammation and reduced IL-6 levels (254 +/- 22 and 2,812 +/- 500 pg/ml in CBD and control rats, respectively, P < 0.01). In isolated hearts, no significant difference in infarct size, left ventricular developed pressures during ischemia and reperfusion, or coronary flow could be detected between CBD-treated and control hearts. Our study shows that CBD induces a substantial in vivo cardioprotective effect from ischemia that is not observed ex vivo. Inasmuch as CBD has previously been administered to humans without causing side effects, it may represent a promising novel treatment for myocardial ischemia.

  1. Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury

    PubMed Central

    Conklin, Daniel J.; Guo, Yiru; Jagatheesan, Ganapathy; Kilfoil, Peter; Haberzettl, Petra; Hill, Bradford G.; Baba, Shahid P.; Guo, Luping; Wetzelberger, Karin; Obal, Detlef; Rokosh, D. Gregg; Prough, Russell A.; Prabhu, Sumanth D.; Velayutham, Murugesan; Zweier, Jay L.; Hoetker, David; Riggs, Daniel W.; Srivastava, Sanjay; Bolli, Roberto; Bhatnagar, Aruni

    2016-01-01

    Rationale Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed. Objective We tested the hypothesis that removal of aldehydes by glutathione S-transferase P (GSTP) diminishes I/R injury. Methods and Results In adult male C57BL/6 mouse hearts, Gstp1/2 was the most abundant GST transcript followed by Gsta4 and Gstm4.1, and GSTP activity was a significant fraction of the total GST activity. mGstp1/2 deletion reduced total GST activity, but no compensatory increase in GSTA and GSTM or major antioxidant enzymes was observed. Genetic deficiency of GSTP did not alter cardiac function, but in comparison with hearts from wild-type (WT) mice, the hearts isolated from GSTP-null mice were more sensitive to I/R injury. Disruption of the GSTP gene also increased infarct size after coronary occlusion in situ. Ischemia significantly increased acrolein in hearts, and GSTP deficiency induced significant deficits in the metabolism of the unsaturated aldehyde, acrolein, but not in the metabolism 4-hydroxy-trans-2-nonenal (HNE) or trans-2-hexanal; and, upon ischemia, the GSTP-null hearts accumulated more acrolein-modified proteins than WT hearts. GSTP-deficiency did not affect I/R-induced free radical generation, JNK activation or depletion of reduced glutathione. Acrolein-exposure induced a hyperpolarizing shift in INa, and acrolein-induced cell death was delayed by SN-6, a Na+/Ca++ exchange inhibitor. Cardiomyocytes isolated from GSTP-null hearts were more sensitive than WT myocytes to acrolein-induced protein crosslinking and cell death. Conclusions GSTP protects the heart from I/R injury by facilitating the detoxification of cytotoxic aldehydes such as acrolein. PMID:26169370

  2. Effect of ivabradine on left ventricular remodelling after reperfused myocardial infarction: A pilot study.

    PubMed

    Gerbaud, Edouard; Montaudon, Michel; Chasseriaud, Warren; Gilbert, Stephen; Cochet, Hubert; Pucheu, Yann; Horovitz, Alice; Bonnet, Jacques; Douard, Hervé; Coste, Pierre

    2014-01-01

    Heart rate is a major determinant of myocardial oxygen demand; in ST-segment elevation myocardial infarction (STEMI), patients treated with primary percutaneous intervention (PPCI), heart rate at discharge correlates with mortality. Ivabradine is a pure heart rate-reducing agent that has no effect on blood pressure and contractility, and can reverse left ventricular (LV) remodelling in patients with heart failure. To evaluate whether ivabradine, when added to current guideline-based therapy, improves LV remodelling in STEMI patients treated with PPCI. This paired-cohort study included 124 patients between June 2011 and July 2012. Ivabradine (5mg twice daily) was given promptly after PPCI, along with beta-blockers, to obtain a heart rate<60 beats per minute (ivabradine group). This group was matched with STEMI patients treated in line with current guidelines, including beta-blockers (bisoprolol), according to age, sex, infarct-related coronary artery, ischaemia time and infarct size determined by initial cardiac magnetic resonance imaging (CMR) (control group). Statistical analyses were performed according to an intention-to-continue treatment principle. CMR data at 3 months were available for 122 patients. Heart rate was lower in the ivabradine group than in the control group during the initial CMR (P=0.02) and the follow-up CMR (P=0.006). At the follow-up CMR, there was a smaller increase in LV end-diastolic volume index in the ivabradine group than in the control group (P=0.04). LV end-systolic volume index remained unchanged in the ivabradine group, but increased in the control group (P=0.01). There was a significant improvement in LV ejection fraction in the ivabradine group compared with in the control group (P=0.04). In successfully reperfused STEMI patients, ivabradine may improve LV remodelling when added to current guideline-based therapy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. Myocardial ischemic-reperfusion injury in a rat model of metabolic syndrome.

    PubMed

    Mozaffari, Mahmood S; Schaffer, Stephen W

    2008-10-01

    Hearts of NaCl-induced hypertensive-glucose intolerant (HGI) rats develop reduced infarcts after ischemia-reperfusion injury (IRI) than their hypertensive (H) counterparts. Because high intake of saturated fat is a major risk factor for ischemic heart disease, we tested the hypothesis that chronic (18 weeks) consumption of a high saturated fat diet increases susceptibility to IRI, an effect more marked in the HGI rats than in the H rats. The fat-fed H (HFAT) rat displayed significantly higher body weight and plasma leptin content compared to the H, HGI, or fat-fed HGI (HGIFAT) rats which all showed similar values. In contrast, plasma triglyceride concentration was significantly higher in the HGIFAT rat than in the other three groups. Plasma insulin concentration was similar in the two H groups but higher than that of the two HGI groups. Compared to the H rat, the HGI rat was markedly glucose intolerant, with fat feeding causing comparable worsening of glucose intolerance in each group. The HGIFAT rats displayed a reduction in baseline myocardial contractility and relaxation and a higher end-diastolic pressure compared to the other three groups. Infarct size was significantly lower in the HGI rats than in the H rats. Although fat feeding did not affect infarct size of the H rat, it worsened that of the HGIFAT rat thereby abrogating the differential that existed between the H and HGI rats. In conclusion, excess fat feeding impairs myocardial function of HGI rats and increases their susceptibility to IRI. These findings are of relevance to the metabolic syndrome that manifests as a cluster of insulin resistance, dyslipidemia, and systemic hypertension.

  4. The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury

    PubMed Central

    Chen-Scarabelli, Carol; Agrawal, Pratik R.; Saravolatz, Louis; Abuniat, Cadigia; Scarabelli, Gabriele; Stephanou, Anastasis; Loomba, Leena; Narula, Jagat; Scarabelli, Tiziano M.; Knight, Richard

    2014-01-01

    A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cytoplasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion (I/R) injury. This tightly orchestrated catabolic cellular ‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protective mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the variability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin (mTOR) inhibitors, adenosine monophosphate-activated protein kinase (AMPK) modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic manipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling. PMID:25593583

  5. Intermedin protects against myocardial ischemia-reperfusion injury in diabetic rats

    PubMed Central

    2013-01-01

    Background Diabetic patients, through incompletely understood mechanisms, endure exacerbated ischemic heart injury compared to non-diabetic patients. Intermedin (IMD) is a novel calcitonin gene-related peptide (CGRP) superfamily member with established cardiovascular protective effects. However, whether IMD protects against diabetic myocardial ischemia/reperfusion (MI/R) injury is unknown. Methods Diabetes was induced by streptozotocin in Sprague–Dawley rats. Animals were subjected to MI via left circumflex artery ligation for 30 minutes followed by 2 hours R. IMD was administered formally 10 minutes before R. Outcome measures included left ventricular function, oxidative stress, cellular death, infarct size, and inflammation. Results IMD levels were significantly decreased in diabetic rats compared to control animals. After MI/R, diabetic rats manifested elevated intermedin levels, both in plasma (64.95 ± 4.84 pmol/L, p < 0.05) and myocardial tissue (9.8 ± 0.60 pmol/L, p < 0.01) compared to pre-MI control values (43.62 ± 3.47 pmol/L and 4.4 ± 0.41). IMD administration to diabetic rats subjected to MI/R decreased oxidative stress product generation, apoptosis, infarct size, and inflammatory cytokine release (p < 0.05 or p < 0.01). Conclusions By reducing oxidative stress, inflammation, and apoptosis, IMD may represent a promising novel therapeutic target mitigating diabetic ischemic heart injury. PMID:23777472

  6. Lysophosphatidic Acid Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury in the Immature Hearts of Rats

    PubMed Central

    Chen, Haibo; Liu, Si; Liu, Xuewen; Yang, Jinjing; Wang, Fang; Cong, Xiangfeng; Chen, Xi

    2017-01-01

    The cardioprotection of the immature heart during cardiac surgery remains controversial due to the differences between the adult heart and the newborn heart. Lysophosphatidic acid (LPA) is a small bioactive molecule with diverse functions including cell proliferation and survival via its receptor: LPA1–LPA6. We previously reported that the expressions of LPA1 and LPA3 in rat hearts were much higher in immature hearts and then declined rapidly with age. In this study, we aimed to investigate whether LPA signaling plays a potential protective role in immature hearts which had experienced ischemia/reperfusion (I/R) injury. The results showed that in Langendorff-perfused immature rat hearts (2 weeks), compared to I/R group, LPA pretreatment significantly enhanced the cardiac function, attenuated myocardial infarct size and CK-MB release, decreased myocardial apoptosis and increased the expression of pro-survival signaling molecules. All these effects could be abolished by Ki16425, an antagonist to LPA1 and LPA3. Similarly, LPA pretreatment protected H9C2 from hypoxia-reoxygenation (H/R) induced apoptosis and necrosis in vitro. The mechanisms underlying the anti-apoptosis effects were related to activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinas B (AKT) signaling pathways as well as phosphorylation of the downstream effector of AKT, glycogen synthase kinase 3 beta (GSK3β), through LPA1 and/or LPA3. What's more, we found that LPA preconditioning increased glucose uptake of H9C2 subjected to H/R by the activation of AMP-Activated Protein Kinase (AMPK) but not the translocation of GLUT4. In conclusion, our study indicates that LPA is a potent survival factor for immature hearts against I/R injuries and has the potential therapeutic function as a cardioplegia additive for infantile cardiac surgery. PMID:28377726

  7. Educational Level and Long-term Mortality in Patients With Acute Myocardial Infarction.

    PubMed

    Consuegra-Sánchez, Luciano; Melgarejo-Moreno, Antonio; Galcerá-Tomás, José; Alonso-Fernández, Nuria; Díaz-Pastor, Ángela; Escudero-García, Germán; Jaulent-Huertas, Leticia; Vicente-Gilabert, Marta

    2015-11-01

    The value of socioeconomic status as a prognostic marker in acute myocardial infarction is controversial. The aim of this study was to evaluate the impact of educational level, as a marker of socioeconomic status, on the prognosis of long-term survival after acute myocardial infarction. We conducted a prospective, observational study of 5797 patients admitted to hospital with acute myocardial infarction. We studied long-term all-cause mortality (median 8.5 years) using adjusted regression models. We found that 73.1% of patients had primary school education (n=4240), 14.5% had secondary school education (including high school) (n=843), 7.0% was illiterate (n=407), and 5.3% had higher education (n=307). Patients with secondary school or higher education were significantly younger, more were male, and they had fewer risk factors and comorbidity. These patients arrived sooner at hospital and had less severe heart failure. During admission they received more reperfusion therapy and their crude mortality was lower. Their drug treatment in hospital and at discharge followed guideline recommendations more closely. On multivariate analysis, secondary school or higher education was an independent predictor and protective factor for long-term mortality (hazard ratio=0.85; 95% confidence interval, 0.74-0.98). Our study shows an inverse and independent relationship between educational level and long-term mortality in patients with acute myocardial infarction. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  8. Progressive failure of coronary flow during reperfusion of myocardial infarction: Documentation of the no reflow phenomenon with positron emission tomography

    SciTech Connect

    Jeremy, R.W.; Links, J.M.; Becker, L.C. )

    1990-09-01

    During reperfusion of a myocardial infarct, development of microvascular occlusion may result in regional hypoperfusion (no reflow) despite a patent infarct-related artery. This study examined the extent and time course of no reflow with use of rubidium-82 positron emission tomography. In 12 anesthetized dogs, the left anterior descending coronary artery was occluded for 90 min and then freely reperfused. Regional myocardial perfusion was imaged by serial rubidium-82 positron emission tomography during coronary occlusion and every 30 min during reperfusion. After 4 h of reperfusion, infarct size and no reflow zone were measured postmortem by triphenyltetrazolium and thioflavin staining, respectively. Perfusion defects evident on rubidium-82 images during coronary occlusion rapidly resolved during the early reflow period. However, a recurrent perfusion defect appeared after 1 to 2 h of reflow in all dogs. The severity of recurrent perfusion defects progressed with time; after 5 min of reflow, relative perfusion in the left anterior descending artery territory was 97 +/- 6% of that in the normal circumflex artery region, but perfusion decreased progressively to 68 +/- 5% after 2 h (p less than 0.05) and to 55 +/- 4% after 4 h of reperfusion (p less than 0.05 versus 2 h). As measured by radioactive tracer microspheres, endocardial blood flow decreased similarly in the postischemic left anterior descending artery region from 1.2 +/- 0.2 ml/min per g after 5 min of reflow to 0.4 +/- 0.1 ml/min per g after 3 h of reflow (p less than 0.01). Residual infarct perfusion, measured by rubidium-82 after 4 h of reflow, was related to both infarct size (r = -0.88) and the extent of the no reflow zone (r = -0.84) in the postmortem left ventricular sections. Thus, serial positron emission tomography with rubidium-82 demonstrates a progressive loss of infarct perfusion.

  9. Electromagnetic field at 15.95-16 Hz is cardio protective following acute myocardial infarction.

    PubMed

    Barzelai, Sharon; Dayan, Anat; Feinberg, Micha S; Holbova, Radka; Laniado, Shlomo; Scheinowitz, Mickey

    2009-10-01

    Previous studies have shown that pre-exposure of the heart to weak magnetic field reduces infarct size shortly after induction of myocardial ischemia. To investigate the role of AC magnetic field with a frequency of 15.95-16 Hz and 80 mT on left ventricular (LV) remodeling following chronic coronary occlusion and a short episode of ischemia followed by reperfusion (I/R). LV dimension and function were measured using echocardiography. Femur bone marrow was isolated and cells were phenotyped for endothelial linage and immuno stained for endothelial cells. The area at risk was measured using triphenyltetrazolium chloride staining. A significant reduction of 27% in shortening fraction (SF) was measured following acute myocardial infarction (AMI) compared with a 7% decrease in animals exposed to magnetic field (p < 0.04). A significantly higher number of colony forming units and endothelial progenitor cells were counted within the treated groups subjected to magnetic field (p < 0.02). Exposing the heart to magnetic field prior to reperfusion did not show any preservation either on SF or on infarct size. Magnetic field was protective in the AMI but not in the I/R model. The mechanisms underlying cardiac protection induced by AC magnetic field following chronic injury deserves further investigation.

  10. Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage

    NASA Astrophysics Data System (ADS)

    Webb, Andrew; Bond, Richard; McLean, Peter; Uppal, Rakesh; Benjamin, Nigel; Ahluwalia, Amrita

    2004-09-01

    Nitric oxide (NO) is thought to protect against the damaging effects of myocardial ischemia-reperfusion injury, whereas xanthine oxidoreductase (XOR) normally causes damage through the generation of reactive oxygen species. In the heart, inorganic nitrite has the potential to act as an endogenous store of NO, liberated specifically during ischemia. Using a detection method that we developed, we report that under ischemic conditions both rat and human homogenized myocardium and the isolated perfused rat heart (Langendorff preparation) generate NO from in a reaction that depends on XOR activity. Functional studies of rat hearts in the Langendorff apparatus showed that nitrite (10 and 100 µM) reduced infarct size from 47.3 ± 2.8% (mean percent of control ± SEM) to 17.9 ± 4.2% and 17.4 ± 1.0%, respectively (P < 0.001), and was associated with comparable improvements in recovery of left ventricular function. This protective effect was completely blocked by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO). In summary, the generation of NO from •, rather than damaging.

  11. Chronic Exercise Downregulates Myocardial Myoglobin and Attenuates Nitrite Reductase Capacity During Ischemia-Reperfusion

    PubMed Central

    Nicholson, Chad K.; Lambert, Jonathan P.; Chow, Chi-Wing; Lefer, David J.; Calvert, John W.

    2013-01-01

    Background The infarct sparing effects of exercise are evident following both long-term and short-term training regimens. Here we compared the infarct-lowering effects of nitrite therapy, voluntary exercise, and the combination of both following myocardial ischemia-reperfusion (MI/R) injury. We also compared the degree to which each strategy increased cardiac nitrite levels, as well as the effects of each strategy on the nitrite reductase activity of the heart. Methods and Results Mice subjected to voluntary wheel running (VE) for 4 weeks displayed an 18% reduction in infarct size when compared to sedentary mice, whereas mice administered nitrite therapy (25 mg/L in drinking water) showed a 53% decrease. However, the combination of VE and nitrite exhibited no further protection than VE alone. Although the VE and nitrite therapy mice showed similar nitrite levels in the heart, cardiac nitrite reductase activity was significantly reduced in the VE mice. Additionally, the cardiac protein expression of myoglobin, a known nitrite reductase, was also reduced after VE. Further studies revealed that cardiac NFAT activity was lower after VE due to a decrease in calcineurin activity and an increase in GSK3β activity. Conclusion These data suggest that VE downregulates cardiac myoglobin levels by inhibiting calcineurin/NFAT signaling. Additionally, these results suggest that the modest infarct sparing effects of VE are the result of a decrease in the hearts ability to reduce nitrite to nitric oxide during MI/R. PMID:23962643

  12. Autophagy protects cardiomyocytes from the myocardial ischaemia-reperfusion injury through the clearance of CLP36

    PubMed Central

    Li, Shiguo; Liu, Chao; Gu, Lei; Wang, Lina; Shang, Yongliang; Liu, Qiong; Wan, Junyi; Shi, Jian; Wang, Fang; Xu, Zhiliang; Ji, Guangju

    2016-01-01

    Cardiovascular disease (CVD) is the leading cause of the death worldwide. An increasing number of studies have found that autophagy is involved in the progression or prevention of CVD. However, the precise mechanism of autophagy in CVD, especially the myocardial ischaemia-reperfusion injury (MI/R injury), is unclear and controversial. Here, we show that the cardiomyocyte-specific disruption of autophagy by conditional knockout of Atg7 leads to severe contractile dysfunction, myofibrillar disarray and vacuolar cardiomyocytes. A negative cytoskeleton organization regulator, CLP36, was found to be accumulated in Atg7-deficient cardiomyocytes. The cardiomyocyte-specific knockout of Atg7 aggravates the MI/R injury with cardiac hypertrophy, contractile dysfunction, myofibrillar disarray and severe cardiac fibrosis, most probably due to CLP36 accumulation in cardiomyocytes. Altogether, this work reveals autophagy may protect cardiomyocytes from the MI/R injury through the clearance of CLP36, and these findings define a novel relationship between autophagy and the regulation of stress fibre in heart. PMID:27512143

  13. Vitamin D and acute myocardial infarction

    PubMed Central

    Milazzo, Valentina; De Metrio, Monica; Cosentino, Nicola; Marenzi, Giancarlo; Tremoli, Elena

    2017-01-01

    Vitamin D deficiency is a prevalent condition, cutting across all ethnicities and among all age groups, and occurring in about 30%-50% of the population. Besides vitamin D established role in calcium homeostasis, its deficiency is emerging as a new risk factor for coronary artery disease. Notably, clinical investigations have suggested that there is an association between hypovitaminosis D and acute myocardial infarction (AMI). Not only has it been linked to incident AMI, but also to increased morbidity and mortality in this clinical setting. Moreover, vitamin D deficiency seems to predispose to recurrent adverse cardiovascular events, as it is associated with post-infarction complications and cardiac remodeling in patients with AMI. Several mechanisms underlying the association between vitamin D and AMI risk can be involved. Despite these observational and mechanistic data, interventional trials with supplementation of vitamin D are controversial. In this review, we will discuss the evidence on the association between vitamin D deficiency and AMI, in terms of prevalence and prognostic impact, and the possible mechanisms mediating it. Further research in this direction is warranted and it is likely to open up new avenues for reducing the risk of AMI. PMID:28163832

  14. Hospital mortality of acute myocardial infarction in the thrombolytic era

    PubMed Central

    Mahon, N; O'Rorke, C; Codd, M; McCann, H; McGarry, K; Sugrue, D

    1999-01-01

    OBJECTIVE—To examine the management and outcome of an unselected consecutive series of patients admitted with acute myocardial infarction to a tertiary referral centre.
DESIGN—A historical cohort study over a three year period (1992-94) of consecutive unselected admissions with acute myocardial infarction identified using the HIPE (hospital inpatient enquiry) database and validated according to MONICA criteria for definite or probable acute myocardial infarction.
SETTING—University teaching hospital and cardiac tertiary referral centre.
RESULTS—1059 patients were included. Mean age was 67 years; 60% were male and 40% female. Rates of coronary care unit (CCU) admission, thrombolysis, and predischarge angiography were 70%, 28%, and 32%, respectively. Overall in-hospital mortality was 18%. Independent predictors of hospital mortality by multivariate analysis were age, left ventricular failure, ventricular arrhythmias, cardiogenic shock, management outside CCU, and reinfarction. Hospital mortality in a small cohort from a non-tertiary referral centre was 14%, a difference largely explained by the lower mean age of these patients (64 years). Five year survival in the cohort was 50%. Only age and left ventricular failure were independent predictors of mortality at follow up.
CONCLUSIONS—In unselected consecutive patients the hospital mortality of acute myocardial infarction remains high (18%). Age and the occurrence of left ventricular failure are major determinants of short and long term mortality after acute myocardial infarction.


Keywords: myocardial infarction; mortality; thrombolysis PMID:10212164

  15. How long do acute coronary syndrome patients wait for reperfusion, diagnostic coronary angiography and surgical revascularisation?

    PubMed

    Voss, Jamie; Martin, Andrew; Caldwell, Imogen; Lee, Mildred; Kerr, Andrew J

    2013-06-14

    To describe the components of in-hospital waiting time to investigation and management in patients with acute coronary syndromes (ACS) admitted to the Middlemore Hospital (MMH) Coronary Care Unit. We examined the time to (1) reperfusion therapy in ST-elevation myocardial infarction (STEMI), (2) coronary angiography in ACS, and (3) surgical revascularisation. Data was collected prospectively for consecutive patients via the Acute PREDICT ACS registry. Of 280 STEMI admissions in 2009 and 2010, 101 underwent primary percutaneous coronary intervention. The median door-to-balloon time when performed on site at MMH was 83 minutes (IQR 69-101 minutes) compared with 135 minutes (IQR 112-165 minutes) for those transferred after hours to Auckland City Hospital (ACH). Of 2115 ACS admissions between 2007 and 2010 84% underwent inpatient coronary angiography and 69% of these underwent this within 3 days. The strongest predictors of a >3 day delay were advanced chronic kidney disease (odds ratio 3.68, 95% CI 2.08-6.51) and presenting late in the week (odds ratio 2.85, 95% CI 2.30-3.54). 329 patients (16%) underwent coronary artery bypass graft surgery (CABG). The median time from admission to inpatient CABG was 13 days and from discharge to outpatient CABG was 155 days. Of ACS patients referred for outpatient surgery in the public sector 38% were readmitted with further ACS whilst waiting. Important delays were identified across the spectrum of post-admission care for ACS patients potentially impacting on both patient outcomes and the cost of care. Active quality improvement programmes to reduce delays are required.

  16. [Acute myocardial infarction complicated by acute pulmonary oedema and cardiogenic collapse during dobutamine stress echocardiography].

    PubMed

    Yameogo, Nobila Valentin; Mbaye, Alassane; Kagambega, Larissa Justine; Dioum, Momar; Diagne-Sow, Dior; Kane, Moussa; Diack, Bouna; Kane, Abdoul

    2013-06-23

    Acute myocardial infarction is a rare complication of dobutamine stress echocardiography. We describe the case of a diabetic patient who presented with an anterior myocardial infarction complicated by an acute pulmonary oedema and cardiogenic collapse during dobutamine stress echocardiography, requiring five days' hospitalisation. Coronarography could not be performed because of inadequate medical facilities.

  17. Is acute reperfusion therapy safe in acute ischemic stroke patients who harbor unruptured intracranial aneurysm?

    PubMed

    Mowla, Ashkan; Singh, Karanbir; Mehla, Sandhya; Ahmed, Mohammad K; Shirani, Peyman; Kamal, Haris; Krishna, Chandan; Sawyer, Robert N; Ching, Marilou; Siddiqui, Adnan H; Levy, Elad I; Snyder, Kenneth V; Crumlish, Annemarie; Hopkins, L N

    2015-10-01

    Intracranial aneurysms are currently considered as contraindication for intravenous thrombolysis in acute ischemic stroke, very likely due to a possible increase in the risk of bleeding from aneurysm rupture; however, there is limited data available on whether intravenous thrombolysis is safe for acute ischemic stroke patients with pre-existing intracranial aneurysms. To find out the safety of intravenous thrombolysis in acute ischemic stroke patients who harbor unruptured intracranial aneurysms. We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with intravenous thrombolysis for acute ischemic stroke in our center from the beginning of 2006 till the end of April 2014. Those with unruptured intracranial aneurysm present on cerebrovascular images prior to acute reperfusion therapy were identified. Post-thrombolysis brain imaging was reviewed to evaluate for any intraparenchymal or subarachnoid hemorrhage related or unrelated to the aneurysm. A total of 637 patients received intravenous thrombolysis for acute ischemic stroke in our center during an 8·3-year period. Thirty-three (5·2%) were found to have at least one intracranial aneurysms. Twenty-three (70%) of those received only intravenous thrombolysis, and 10 patients received combination of intravenous and intra-arterial thrombolysis. The size of the largest aneurysm was 10 mm in maximum diameter (range: 2-10 mm). The mean size of aneurysms was 4·8 mm. No symptomatic intracranial hemorrhage occurred among the 23 patients receiving only intravenous thrombolysis. Out of those who received a combination of intravenous and intra-arterial thrombolysis, one developed symptomatic intracranial hemorrhage in the location of acute infarct, distant to the aneurysm location. Our findings suggest that neither intravenous thrombolysis nor combination of intravenous and intra-arterial thrombolysis increases the risk of aneurysmal hemorrhage in acute ischemic stroke

  18. Erythropoietin pretreatment suppresses inflammation by activating the PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury

    PubMed Central

    RONG, REN; XIJUN, XIAO

    2015-01-01

    Erythropoietin (EPO), a glycoprotein originally known for its important role in the stimulation of erythropoiesis, has recently been shown to have significant protective effects in animal models of kidney and intestinal ischemia-reperfusion injury (IRI). However, the mechanism underlying these protective effects remains unclear. The aim of the current study was to evaluate the effects of EPO on myocardial IRI and to investigate the mechanism underlying these effects. A total of 18 male Sprague Dawley rats were randomly divided into three groups, namely the sham, IRI-saline and IRI-EPO groups. Rats in the IRI-EPO group were administered 5,000 U/kg EPO intraperitoneally 24 h prior to the induction of IRI. IRI was induced by ligating the left descending coronary artery for 30 min, followed by reperfusion for 3 h. Pathological changes in the myocardial tissue were observed and scored. The levels of the proinflammatory cytokines, interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, were evaluated in the serum and myocardial tissue. Furthermore, the effects of EPO on phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling and EPO receptor (EPOR) phosphorylation were measured. Pathological changes in the myocardial tissue, increased expression levels of TNF-α, IL-6 and IL-1β in the myocardium, and increased serum levels of these mediators, as a result of IRI, were significantly decreased by EPO pretreatment. The effects of EPO were found to be associated with the activation of PI3K/Akt signaling, which suppressed the inflammatory responses, following the initiation of EPOR activation by EPO. Therefore, EPO pretreatment was demonstrated to decrease myocardial IRI, which was associated with activation of EPOR, subsequently increasing PI3K/Akt signaling to inhibit the production and release of inflammatory mediators. Thus, the results of the present study indicated that EPO may be useful for preventing myocardial IRI. PMID:26622330

  19. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial.

    PubMed

    Mahaffey, K W; Puma, J A; Barbagelata, N A; DiCarli, M F; Leesar, M A; Browne, K F; Eisenberg, P R; Bolli, R; Casas, A C; Molina-Viamonte, V; Orlandi, C; Blevins, R; Gibbons, R J; Califf, R M; Granger, C B

    1999-11-15

    The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.

  20. Ischemia/reperfusion is an independent trigger for increasing myocardial content of mRNA B-type natriuretic peptide.

    PubMed

    Ramos, Lafayete William F; Murad, Neif; Goto, Eduardo; Antônio, Edinei L; Silva, José A; Tucci, Paulo F; Carvalho, Antônio C

    2009-11-01

    This study aims to determine whether a relation exists between ischemia/reperfusion and myocardial B-type natriuretic peptide (BNP) mRNA expression independent of variations in intracavitary diastolic volume and consequently, of cardiomyocyte stretching. Twenty-three rats were subjected to the following conditions: control (C), 15 min of ischemia (I15), or ischemia plus 15 (R15), 30 (R30), or 45 (R45) min of reperfusion in the in situ hearts. Isolated hearts of sixteen additional rats (sham, n = 8; occlusion, n = 8) were perfused for studies in the absence of ventricular distension. All hearts were divided in two segments (ischemic and nonischemic). Ventricular distension was avoided by excluding the atria and mitral valves. In both experiments, BNP mRNA was quantified by real-time polymerase chain reaction in both nonischemic and ischemic regions. In the in situ hearts, myocardial BNP mRNA values at R15 (4.24 +/- 0.75) in the ischemic region were higher than in other groups (C: 1.43 +/- 0.81, P = 0.044; I15: 3.05 +/- 0.62, P = 0.048; R30: 0.76 +/- 0.84, P = 0.001; R45: 1.47 +/- 0.60, P = 0.046, [analysis of variance]). In isolated hearts without ventricular distension, myocardial BNP mRNA (arbitrary units) content at R15 in ischemic regions (4.54 +/- 0.26) was greater than in nonischemic regions in both occlusion (3.51 +/- 0.20, P < 0.001) and sham (3.38 +/- 0.25, P = 0.0001 and 3.47 +/- 0.19, P = 0.0001) groups. The present data show that ischemia/reperfusion is responsible for increased BNP mRNA myocardial content independent of changes of ventricular cavity diastolic volume.

  1. Moderate hypothermia (30 degrees C) maintains myocardial integrity and modifies response of cell survival proteins after reperfusion.

    PubMed

    Ning, Xue-Han; Chi, Emil Y; Buroker, Norman E; Chen, Shi-Han; Xu, Cheng-Su; Tien, Ying-Tzang; Hyyti, Outi M; Ge, Ming; Portman, Michael A

    2007-10-01

    Hypothermia preserves myocardial function, promotes signaling for cell survival, and inhibits apoptotic pathways during 45-min reperfusion. We tested the hypothesis that signaling at the transcriptional level is followed by corresponding proteomic response and maintenance of structural integrity after 3-h reperfusion. Isolated hearts were Langendorff perfused and exposed to mild (I group; n = 6, 34 degrees C) or moderate (H group; n = 6, 30 degrees C) hypothermia during 120-min total ischemia with cardioplegic arrest and 180-min 37 degrees C reperfusion. Moderate hypothermia suppressed anaerobic metabolism during ischemia and significantly diminished left ventricular end-diastolic pressure at the end of ischemia from 52.7 +/- 3.3 (I group) to 1.8 +/- 0.9 (H group) mmHg. Unlike the I group, which showed poor cardiac function and high left ventricular pressure, the H group showed preservation of myocardial function, coronary flow, and oxygen consumption. Compared with normal control hearts without ischemia (n = 5), histological staining in the I group showed marked disarray and fragmentation of collagen network (score 4-5), while the H group showed preserved collagen integrity (score 0-1). The apoptosis-linked tumor suppressor protein p53 was expressed throughout the I group only (score 4-5). The H group produced elevated expression for hypoxia-inducible factor 1alpha and heme oxygenase 1, but minimally affected vascular endothelial growth factor expression. The H group also elevated expression for survival proteins peroxisomal proliferator-activated receptor-beta and Akt-1. These results show in a constant left ventricular volume model that moderate hypothermia (30 degrees C) decreases myocardial energy utilization during ischemia and subsequently promotes expression of proteins involved in cell survival, while inhibiting induction of p53 protein. These data also show that 34 degrees C proffers less protection and loss of myocardial integrity.

  2. Protective effects of Ping-Lv-Mixture (PLM), a medicinal formula on arrhythmias induced by myocardial ischemia-reperfusion.

    PubMed

    An, Wei; Yang, Jing

    2006-11-03

    Ping-Lv-Mixture (PLM) is a Chinese medicinal formula. The present study aimed to determine the effects of PLM on myocardial ischemia-reperfusion (MI/R) induced arrhythmias in rats. Arrhythmia model was established by occlusion of the left arterial descending coronary artery and thereafter reperfusion. A lead II electrocardiogram was monitored throughout the experiment. The results showed that pretreatment of PLM to MI/R rats significantly reduced the incidence and duration of ventricular tachycardia and ventricular fibrillation. On induction of MI/R, the activities of creatine kinase and lactate dehydrogenase were increased in vehicle group. PLM (0.04-1.00 g/kg) administration prevented the increase of these enzymes. Moreover, a significant increase of myocardium superoxide dismutase and decrease of malondialdehyde contents were observed in rats of PLM groups. On the other hand, the expressions of platelet activating factor (PAF) receptor mRNA was down-regulated in a dose-dependent manner in the PLM-treated groups by RT-PCR. Thus, it can be concluded that pretreatment with PLM inhibited lipid peroxidation in rats through suppressing the expression of PAF receptor, which may contribute to its preventive effect on myocardial ischemia-reperfusion induced arrhythmias.

  3. MiR-146b protects cardiomyocytes injury in myocardial ischemia/reperfusion by targeting Smad4

    PubMed Central

    Di, Yun-Feng; Li, De-Cai; Shen, Yan-Qing; Wang, Chun-Lei; Zhang, Da-Yong; Shang, An-Quan; Hu, Teng

    2017-01-01

    MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, have been implicated as critical regulatory molecules in many cardiovascular diseases, including ischemia-/reperfusion-induced cardiac injury. In the present study, we report on the role of miR-146b in myocardial I/R injury and the underlying cardio-protective mechanism. Antagomir-146b was used to explore the effects of miR-146b on cardiac ischemia/reperfusion injury (30 min ischemia followed by 180 min reperfusion). As predicted, miR-146b overexpression significantly reduced the infarct size and cardiomyocytes apoptosis and release of creatine kinase and lactate dehydrogenase. In addition, miR-146b attenuated H9c2 cell apoptosis. Furthermore, Smad4 was predicted and verified as a potential miR-146b target using bioinformatics and luciferase assay. In summary, this study demonstrated that miR-146b plays a critical protective role in cardiac ischemic injury and may provide a new therapeutic approach for the treatment of myocardial I/R injury.

  4. [Factors influencing mobilisation of endothelial progenitor cells and angiogenic cytokines after an extensive acute myocardial infarction].

    PubMed

    Domínguez-Franco, Antonio; González, Francisco Jesús; Rodríguez-Losada, Noela; Marchal, Juan Antonio; Cabrera-Bueno, Fernando; Carrillo, Esmeralda; Gómez-Doblas, Juan José; Perán, Macarena; Alonso-Briales, Juan H; Jiménez-Navarro, Manuel F; Aránega, Antonia; De Teresa Galván, Eduardo

    2012-04-21

    Following an acute myocardial infarction (AMI), bone-marrow derived endothelial progenitor cells (EPC) are mobilised into the peripheral blood. Our aim was to examine the factors influencing this spontaneous cell mobilisation. In this study we analysed 47 patients with extensive AMI (left ventricular ejection fraction [LVEF] <50% by echocardiography during the first week post-AMI); we studied the peripheral blood EPC populations expressing CD133(+), CD34(+), KDR(+), CXCR4(+), as well as the cytokines VEGF (vascular endothelial growth factor), SDF-1 (stromal cell-derived factor 1) and TSP-1 (thrombospondin 1), measured on day 5±2.5 after AMI. The extension of AMI (CPK peak) correlated with the number of CD133(+) mobilised cells: (r=0.40; P=.011). Patients who did not receive perfusion during the acute phase (34%) had more CD34(+)CXCR4(+) cells with a median (interquartile ranges) of 2,401 (498-7,004) vs. 999 (100-1,600), P=.048, and strong correlations between VEGF and CD133(+)CD34(+)KDR(+) (r=.84; P<.01) and SDF-1 and CD34(+)CXCR4(+) (r=.67; P<.01), and between these 2 cytokines (r=.57; P=.01). In the reperfused patients, the correlation between VEGF and CD133(+)CD34(+)KDR(+) was lower (r=.38; P=.03) and the correlation between SDF-1 and CD34(+)CXCR4(+) and VEGF disappeared. Multivariate analysis showed that a VEGF >7pg/mL (P<.01) predicted the mobilisation of CD133(+)CD34(+)KDR(+), whereas hypertension showed a trend (P=.055). Diabetes (P=.045) predicted the number of CD34(+)CXCR4(+), with reperfusion treatment showing a trend in this subpopulation (P=.054). Mobilisation of progenitor cells after AMI is influenced by factors such as diabetes and the cytokine VEGF. Hypertension and reperfusion therapy during the acute phase also tend to influence the cell response. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  5. Predictors and in-hospital prognosis of recurrent acute myocardial infarction

    PubMed Central

    Cao, Cheng-Fu; Li, Su-Fang; Chen, Hong; Song, Jun-Xian

    2016-01-01

    Objective To investigate the contributing factors and in-hospital prognosis of patients with or without recurrent acute myocardial infarction (AMI). Methods A total of 1686 consecutive AMI patients admitted to Peking University People's Hospital from January 2010 to December 2015 were recruited. Their clinical characteristics were retrospectively compared between patients with or without a recurrent AMI. Then multivariable logistic regression was used to estimate the predictors of recurrent myocardial infarction. Results Recurrent AMI patients were older (69.3 ± 11.5 vs. 64.7 ± 12.8 years, P < 0.001) and had a higher prevalence of diabetes mellitus (DM) (52.2% vs. 35.0%, P < 0.001) compared with incident AMI patients, they also had worse heart function at admission, more severe coronary disease and lower reperfusion therapy. Age (OR = 1.03, 95% CI: 1.02–1.05; P < 0.001), DM (OR = 1.86, 95% CI: 1.37–2.52; P < 0.001) and reperfusion therapy (OR = 0.74; 95% CI: 0.52–0.89; P < 0.001) were independent risk factors for recurrent AMI. Recurrent AMI patients had a higher in-hospital death rate (12.1% vs. 7.8%, P = 0.039) than incident AMI patients. Conclusions Recurrent AMI patients presented with more severe coronary artery conditions. Age, DM and reperfusion therapy were independent risk factors for recurrent AMI, and recurrent AMI was related with a high risk of in-hospital death. PMID:27928225

  6. Mitochondrially targeted Endonuclease III has a powerful anti-infarct effect in an in vivo rat model of myocardial ischemia/reperfusion

    PubMed Central

    Yang, Xi-Ming; Cui, Lin; White, James; Kuck, Jamie; Ruchko, Mykhaylo V.; Wilson, Glenn L.; Alexeyev, Mikhail; Gillespie, Mark N.; Downey, James M.

    2016-01-01

    Recent reports indicate that elevating DNA glycosylase/AP lyase repair enzyme activity offers marked cytoprotection in cultured cells and a variety of injury models. In this study, we measured the effect of EndoIII, a fusion protein construct that traffics Endonuclease III, a DNA glycosylase/AP lyase, to the mitochondria, on infarct size in a rat model of myocardial ischemia/reperfusion. Open-chest, anesthetized rats were subjected to 30 min of occlusion of a coronary artery followed by 2 h of reperfusion. An intravenous bolus of EndoIII, 8 mg/kg, just prior to reperfusion reduced infarct size from 43.8 ± 1.4 % of the risk zone in control animals to 24.0 ± 1.3 % with no detectable hemodynamic effect. Neither EndoIII’s vehicle nor an enzymatically inactive EndoIII mutant (K120Q) offered any protection. The magnitude of EndoIII’s protection was comparable to that seen with the platelet aggregation inhibitor cangrelor (25.0 ± 1.8 % infarction of risk zone). Because loading with a P2Y12 receptor blocker to inhibit platelets is currently the standard of care for treatment of acute myocardial infarction, we tested whether EndoIII could further reduce infarct size in rats treated with a maximally protective dose of cangrelor. The combination reduced infarct size to 15.1 ± 0.9 % which was significantly smaller than that seen with either cangrelor or EndoIII alone. Protection from cangrelor but not EndoIII was abrogated by pharmacologic blockade of phosphatidylinositol-3 kinase or adenosine receptors indicating differing cellular mechanisms. We hypothesized that EndoIII protected the heart from spreading necrosis by preventing the release of proinflammatory fragments of mitochondrial DNA (mtDNA) into the heart tissue. In support of this hypothesis, an intravenous bolus at reperfusion of deoxyribonuclease I (DNase I) which should degrade any DNA fragments escaping into the extracellular space was as protective as EndoIII. Furthermore, the combination of EndoIII and

  7. Chronic Losartan Treatment Up-Regulates AT1R and Increases the Heart Vulnerability to Acute Onset of Ischemia and Reperfusion Injury in Male Rats.

    PubMed

    Song, Minwoo A; Dasgupta, Chiranjib; Zhang, Lubo

    2015-01-01

    Inhibition of angiotensin II type 1 receptor (AT1R) is an important therapy in the management of hypertension, particularly in the immediate post-myocardial infarction period. Yet, the role of AT1R in the acute onset of myocardial ischemia and reperfusion injury still remains controversial. Thus, the present study determined the effects of chronic losartan treatment on heart ischemia and reperfusion injury in rats. Losartan (10 mg/kg/day) was administered to six-month-old male rats via an osmotic pump for 14 days and hearts were then isolated and were subjected to ischemia and reperfusion injury in a Langendorff preparation. Losartan significantly decreased mean arterial blood pressure. However, heart weight, left ventricle to body weight ratio and baseline cardiac function were not significantly altered by the losartan treatment. Of interest, chronic in vivo losartan treatment significantly increased ischemia-induced myocardial injury and decreased post-ischemic recovery of left ventricular function. This was associated with significant increases in AT1R and PKCδ expression in the left ventricle. In contrast, AT2R and PKCε were not altered. Furthermore, losartan treatment significantly increased microRNA (miR)-1, -15b, -92a, -133a, -133b, -210, and -499 expression but decreased miR-21 in the left ventricle. Of importance, addition of losartan to isolated heart preparations blocked the effect of increased ischemic-injury induced by in vivo chronic losartan treatment. The results demonstrate that chronic losartan treatment up-regulates AT1R/PKCδ and alters miR expression patterns in the heart, leading to increased cardiac vulnerability to ischemia and reperfusion injury.

  8. Earlier reperfusion in patients with ST-elevation Myocardial infarction by use of helicopter

    PubMed Central

    2012-01-01

    Background In patients with ST-elevation myocardial infarction (STEMI) reperfusion therapy should be initiated as soon as possible. This study evaluated whether use of a helicopter for transportation of patients is associated with earlier initiation of reperfusion therapy. Material and methods A prospective study was conducted, including patients with STEMI and symptom duration less than 12 hours, who had primary percutaneous coronary intervention (PPCI) performed at Aarhus University Hospital in Skejby. Patients with a health care system delay (time from emergency call to first coronary intervention) of more than 360 minutes were excluded. The study period ran from 1.1.2011 until 31.12.2011. A Western Denmark Helicopter Emergency Medical Service (HEMS) project was initiated 1.6.2011 for transportation of patients with time-critical illnesses, including STEMI. Results The study population comprised 398 patients, of whom 376 were transported by ambulance Emergency Medical Service (EMS) and 22 by HEMS. Field-triage directly to the PCI-center was used in 338 of patients. The median system delay was 94 minutes among those field-triaged, and 168 minutes among those initially admitted to a local hospital. Patients transported by EMS and field-triaged were stratified into four groups according to transport distance from the scene of event to the PCI-center: ≤25 km., 26–50 km., 51–75 km. and > 75 km. For these groups, the median system delay was 78, 89, 99, and 141 minutes. Among patients transported by HEMS and field-triaged the estimated median transport distance by ground transportation was 115 km, and the observed system delay was 107 minutes. Based on second order polynomial regression, it was estimated that patients with a transport distance of >60 km to the PCI-center may benefit from helicopter transportation, and that transportation by helicopter is associated with a system delay of less than 120 minutes even at a transport distance up to 150 km

  9. 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

  10. Reducing myocardial infarct size: challenges and future opportunities.

    PubMed

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

    2016-03-01

    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.

  11. Time from first medical contact to reperfusion in ST elevation myocardial infarction: A Which Early ST Elevation Myocardial Infarction Therapy (WEST) substudy

    PubMed Central

    Bata, Iqbal; Armstrong, Paul W; Westerhout, Cynthia M; Travers, Andrew; Sookram, Sunil; Caine, Edward; Christenson, James; Welsh, Robert C

    2009-01-01

    BACKGROUND Recent research and contemporary ST elevation myocardial infarction guidelines emphasize the importance of prompt reperfusion and have redefined the traditional time to treatment metric to include prehospital paramedical staff as the point of first medical contact. However, an important knowledge gap exists relating to data systematically addressing the impact of arrival at the hospital by ambulance and the delays inherent in transfer from a community hospital to tertiary centres for percutaneous coronary intervention (PCI). METHODS The Which Early ST Elevation Myocardial Infarction Therapy (WEST) study initiated treatment at the point of first medical contact, including prehospital contact. Patients were randomly assigned to receive fibrinolysis with usual care or coupled with mechanical cointervention, or primary PCI. To assess the impact of this strategy on time to treatment, the following randomly assigned patient groups were compared: prehospital versus in-hospital; those arriving at the hospital by ambulance versus ambulatory self transport; and those whose initial hospital care was a community versus PCI centre. RESULTS Of the 328 patients enrolled in the study, 221 received fibrinolysis and 107 received primary PCI. Compared with the in-hospital group, patients who underwent prehospital random assignment (44%, n=145) experienced a 48 min reduction in median (interquartile range) time from symptom onset to first study medication (87 min [65 min to 147 min] versus 135 min [95 min to 186 min]; P<0.001) and a 56 min reduction in time to first balloon inflation (148 min [117 min to 214 min] versus 204 min [166 min to 290 min]; P<0.001). Arrival by ambulance without prehospital random assignment (n=90) incurred a substantial delay from first medical contact to reperfusion (fibrinolysis 76 min [63 min to 105 min] and PCI 160 min [141 min to 212 min]) compared with prehospital random assignment (n=145; fibrinolysis 43 min [33 min to 54 min] and PCI 105

  12. [Early statin therapy in acute myocardial infarction].

    PubMed

    Ruiz-Bailén, M; Romero-Bermejo, F J; Expósito-Ruiz, M; Zamora-Zamora, F; Martínez-Ramírez, M J; Castillo-Rivera, A M; Ramos-Cuadra, J A; Ramírez-Sánchez, M; Vázquez-García, R

    2014-01-01

    To evaluate the effects of the early administration of statins during acute myocardial infarction (MI). A retrospective cohort study was carried out. National (Spain). Patients included in the ARIAM registry from January 1999 to December 2008 with a diagnosis of MI. None. We used logistic regression analysis and propensity scoring to determine whether the administration of statins during the first 24h of MI acts as a protective factor against: 1) mortality, 2) the incidence of lethal arrhythmias, or 3) cardiogenic shock. A total of 36 842 patients were included in the study. Statins were administered early in 50.2% of the patients. Statin administration was associated with younger patients with known previous dyslipidemia, obesity, a history of ischemic heart disease, heart failure, presence of sinus tachycardia, use of beta-blockers, angiotensin-converting enzyme inhibitors, thrombolysis and percutaneous coronary intervention. Mortality was 8.2% (13.2% without statin versus 3% with statin, P<.001). Multivariate analysis demonstrated that statin administration acted as a protective factor against mortality (adjusted OR 0.518, 95%CI 0.447 to 0.601). Continued use of statins was associated with a reduction in mortality (adjusted OR 0.597, 95%CI 0.449 to 0.798), and the start of treatment was a protective factor against mortality (adjusted OR 0.642, 95%CI 0.544 -0.757). Statin therapy also exerted a protective effect against the incidence of lethal arrhythmias and cardiogenic shock. These results suggest that early treatment with statins in patients with MI is associated with reduced mortality. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  13. Pharmacological Inhibition of NLRP3 Inflammasome Attenuates Myocardial Ischemia/Reperfusion Injury by Activation of RISK and Mitochondrial Pathways

    PubMed Central

    Tullio, Francesca; Femminò, Saveria; Nigro, Debora; Chiazza, Fausto; Collotta, Debora; Cocco, Mattia; Bertinaria, Massimo; Aragno, Manuela

    2016-01-01

    Although the nucleotide-binding oligomerization domain- (NOD-) like receptor pyrin domain containing 3 (NLRP3) inflammasome has been recently detected in the heart, its role in cardiac ischemia/reperfusion (IR) is still controversial. Here, we investigate whether a pharmacological modulation of NLRP3 inflammasome exerted protective effects in an ex vivo model of IR injury. Isolated hearts from male Wistar rats (5-6 months old) underwent ischemia (30 min) followed by reperfusion (20 or 60 min) with and without pretreatment with the recently synthetized NLRP3 inflammasome inhibitor INF4E (50 μM, 20 min before ischemia). INF4E exerted protection against myocardial IR, shown by a significant reduction in infarct size and lactate dehydrogenase release and improvement in postischemic left ventricular pressure. The formation of the NLRP3 inflammasome complex was induced by myocardial IR and attenuated by INF4E in a time-dependent way. Interestingly, the hearts of the INF4E-pretreated animals displayed a marked improvement of the protective RISK pathway and this effect was associated increase in expression of markers of mitochondrial oxidative phosphorylation. Our results demonstrate for the first time that INF4E protected against the IR-induced myocardial injury and dysfunction, by a mechanism that involves inhibition of the NLRP3 inflammasome, resulting in the activation of the prosurvival RISK pathway and improvement in mitochondrial function. PMID:28053692

  14. Ventricular Assist Device in Acute Myocardial Infarction

    PubMed Central

    Achary, Deepak; Loyaga-Rendon, Renzo Y.; Pamboukian, Salpy V.; Tallaj, Jose A.; Holman, William L.; Cantor, Ryan S.; Naftel, David C.; Kirklin, James K.

    2016-01-01

    Background Patients with acute myocardial infarction (AMI) complicated by acute heart failure or cardiogenic shock have high mortality with conventional management. Objectives We evaluated outcomes of patients with AMI who received durable ventricular assist devices (VADs). Methods Patients with AMI in the INTERMACS registry who underwent VAD placement were included and compared to patients who received VADs for non-AMI indications. Results VADs were implanted in 502 patients with AMI: 443 left ventricular assist devices; 33 biventricular assist devices; and 26 total artificial hearts. Median age was 58.3 years, and 77.1% were male. At implant, 66% were INTERMACS profile 1. A higher proportion of AMI than non- AMI patients had preoperative intra-aortic balloon pumps (57.6% vs. 25.3%; p < 0.01), intubation (58% vs. 8.3%; p < 0.01), extracorporeal membrane oxygenation (17.9% vs. 1.7%, p < 0.01), cardiac arrest (33.5% vs. 3.3%, p < 0.01), and higher-acuity INTERMACS profiles. At 1 month post-VAD, 91.8% of AMI patients were alive with ongoing device support, 7.2 % had died on device, and 1% had been transplanted. At 1 year post-VAD, 52% of AMI patients were alive with ongoing device support, 25.7% had been transplanted, 1.6% had LVADs explanted for recovery, and 20.7% had died on device. The AMI group had higher unadjusted early-phase hazard (HR: 1.24; p = 0.04) and reduced late-phase hazard of death (HR: 0.57; p = 0.04) than the non-AMI group. After accounting for established risk factors, the AMI group no longer had higher early mortality hazard (HR: 0.89; p = 0.3), but had lower late mortality hazard (HR: 0.55; p = 0.02). Conclusion Patients with AMI who receive VADs have outcomes similar to other VAD populations, despite being more critically ill pre-implantation. VAD therapy is an effective strategy for patients with AMI in whom medical therapy is failing. PMID:27102502

  15. Horizontal ECG in acute anterolateral myocardial infarction.

    PubMed

    Erdogan, Okan; Dalkilic, Bahar; Kepez, Alper

    2016-07-01

    The present study aims to compare the amount of ST segment changes recorded by horizontal electrocardiography (hECG) with standard ECG (sECG) in patients with acute anterior and/or lateral ST segment elevation myocardial infarction (STEMI). Consecutive eligible patients (n = 58) who were diagnosed with acute anterior and/or lateral STEMI were included in the study. After recording simultaneous sECG and hECG by placing precordial leads (V3-6) horizontally on the left 4th intercostal space, ST segment changes were compared. The mean ST segment changes (mV) on hECG were significantly higher than sECG in V4 (0.27 ± 0.2 vs. 0.21 ± 0.21, p = 0.001), V5 (0.21 ± 0.17 vs. 0.12 ± 0.16, p < 0.001) and V6 (0.09 ± 0.1 vs. 0.04 ± 0.12, p < 0.001), respectively. When hECG and sECG were compared in patients with BMI < 30 kg/m(2), mean ST segment changes (mV) on hECG were significantly higher than sECG in V4 (0.29 ± 0.21 vs. 0.21 ± 0.24, p = 0.004), V5 (0.22 ± 0.19 vs. 0.13 ± 0.17, p < 0.001) and V6 (0.11 ± 0.11 vs. 0.04 ± 0.11, p < 0.001), respectively. Mean ST segment changes in patients with anterior and/or lateral STEMI were significantly higher and easily detectable on hECG compared with sECG. We suggest that hECG be used in conjunction with sECG to diagnose anterior and lateral wall STEMI in cases of diagnostic doubt.

  16. Incidence of acute myocardial infarction in patients with exercise-induced silent myocardial ischemia

    SciTech Connect

    Assey, M.E.; Walters, G.L.; Hendrix, G.H.; Carabello, B.A.; Usher, B.W.; Spann, J.F. Jr.

    1987-03-01

    Fifty-five patients with angiographically proved coronary artery disease (CAD) underwent Bruce protocol exercise stress testing with thallium-201 imaging. Twenty-seven patients (group I) showed myocardial hypoperfusion without angina pectoris during stress, which normalized at rest, and 28 patients (group II) had a similar pattern of reversible myocardial hypoperfusion but also had angina during stress. Patients were followed for at least 30 months. Six patients in group I had an acute myocardial infarction (AMI), 3 of whom died, and only 1 patient in group II had an AMI (p = 0.05), and did not die. Silent myocardial ischemia uncovered during exercise stress thallium testing may predispose to subsequent AMI. The presence of silent myocardial ischemia identified in this manner is of prognostic value, independent of angiographic variables such as extent of CAD and left ventricular ejection fraction.

  17. [Thrombolysis by tissue plasminogen activator in acute myocardial infarct].

    PubMed

    Keltai, M; Dékány, P; Németh, J; Palik, I; Sitkei, E; Szente, A; Arvay, A

    1991-09-15

    The authors participated in the European multicenter investigation, ESPRIT, organized by the Wellcome Research Laboratories. Thrombolytic treatment by intravenous tissue plasminogen activator was performed in 25 patients with early (less than 6h) myocardial infarction. The efficacy of the treatment was controlled by repeat coronary arteriography at 60 minutes, at 90 minutes and at 24 hours of the tpA treatment. The infarct related artery was reperfused in 9/25 patients at 60 minutes, in 16/25 at 90 minutes and 17/18 at 24 hours. Four patients died after unsuccessful treatment or reocclusion. In two patients significant bleeding occurred at the puncture site but no transfusion was required. No other untoward effect was registered. The left ventricular function did not change significantly during the first day of infarction. It is concluded, that tpA is a safe thrombolytic agent in myocardial infarction. Its thrombolytic efficacy is similar to that of streptokinase.

  18. The impact of numeric and graphic displays of ST-segment deviation levels on cardiologists' decisions of reperfusion therapy for patients with acute coronary occlusion.

    PubMed

    Nimmermark, Magnus O; Wang, John J; Maynard, Charles; Cohen, Mauricio; Gilcrist, Ian; Heitner, John; Hudson, Michael; Palmeri, Sebastian; Wagner, Galen S; Pahlm, Olle

    2011-01-01

    The study purpose is to determine whether numeric and/or graphic ST measurements added to the display of the 12-lead electrocardiogram (ECG) would influence cardiologists' decision to provide myocardial reperfusion therapy. Twenty ECGs with borderline ST-segment deviation during elective percutaneous coronary intervention and 10 controls before balloon inflation were included. Only 5 of the 20 ECGs during coronary balloon occlusion met the 2007 American Heart Association guidelines for ST-elevation myocardial infarction (STEMI). Fifteen cardiologists read 4 sets of these ECGs as the basis for a "yes/no" reperfusion therapy decision. Sets 1 and 4 were the same 12-lead ECGs alone. Set 2 also included numeric ST-segment measurements, and set 3 included both numeric and graphically displayed ST measurements ("ST Maps"). The mean (range) positive reperfusion decisions were 10.6 (2-15), 11.4 (1-19), 9.7 (2-14), and 10.7 (1-15) for sets 1 to 4, respectively. The accuracies of the observers for the 5 STEMI ECGs were 67%, 69%, and 77% for the standard format, the ST numeric format, and the ST graphic format, respectively. The improved detection rate (77% vs 67%) with addition of both numeric and graphic displays did achieve statistical significance (P < .025). The corresponding specificities for the 10 control ECGs were 85%, 79%, and 89%, respectively. In conclusion, a wide variation of reperfusion decisions was observed among clinical cardiologists, and their decisions were not altered by adding ST deviation measurements in numeric and/or graphic displays. Acute coronary occlusion detection rate was low for ECGs meeting STEMI criteria, and this was improved by adding ST-segment measurements in numeric and graphic forms. These results merit further study of the clinical value of this technique for improved acute coronary occlusion treatment decision support. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2016-01-01

    Aims To assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI). Methods and results We performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (mean ± SD age 59 ± 12 years, 74% male) who underwent CMR 2 days and 6 months post-myocardial infarction (n = 267). Native T1 was measured in myocardial regions of interest (n = 288). Adverse remodelling was defined as an increase in left ventricular (LV) end-diastolic volume ≥20% at 6 months. All-cause death or first heart failure hospitalization was a pre-specified outcome that was assessed during follow-up (median duration 845 days). One hundred and sixty (56%) patients had a hypo-intense infarct core disclosed by native T1. In multivariable regression, infarct core native T1 was inversely associated with adverse remodelling [odds ratio (95% confidence interval (CI)] per 10 ms reduction in native T1: 0.91 (0.82, 0.00); P = 0.061). Thirty (10.4%) of 288 patients died or experienced a heart failure event and 13 of these events occurred post-discharge. Native T1 values (ms) within the hypo-intense infarct core (n = 160 STEMI patients) were inversely associated with the risk of all-cause death or first hospitalization for heart failure post-discharge (for a 10 ms increase in native T1: hazard ratio 0.730, 95% CI 0.617, 0.863; P < 0.001) including after adjustment for left ventricular ejection fraction, infarct core T2 and myocardial haemorrhage. The prognostic results for microvascular obstruction were similar. Conclusion Infarct core native T1 represents a novel non-contrast CMR biomarker with potential for infarct characterization and prognostication in STEMI survivors. Confirmatory studies are warranted. ClinicalTrials.gov identifier NCT02072850. PMID:26261290

  20. Increased Sensitivity to Heparin Following Acute Myocardial Infarction

    PubMed Central

    Dufault, C.

    1965-01-01

    In vivo increased sensitivity to heparin has been demonstrated in patients following an acute myocardial infarction. An intravenous injection of 10,000 units of heparin was given to each of 18 patients with recent myocardial infarction in order to compare them with 17 patients who were not suffering from any acute illness. The changes in whole blood clotting time, recalcified plasma clotting time and prothrombin time were greater and more prolonged in the patients with recent myocardial infarction. Of the three tests, the one-stage prothrombin time provided the simplest and the most precise measurement of heparin sensitivity. The reason for this was not clear: it is possible that it is related to shock and congestive heart failure which were complications of the clinical course following myocardial infarction. PMID:14216140

  1. Across-Species Transfer of Protection by Remote Ischemic Preconditioning With Species-Specific Myocardial Signal Transduction by Reperfusion Injury Salvage Kinase and Survival Activating Factor Enhancement Pathways.

    PubMed

    Skyschally, Andreas; Gent, Sabine; Amanakis, Georgios; Schulte, Christiane; Kleinbongard, Petra; Heusch, Gerd

    2015-07-17

    Reduction of myocardial infarct size by remote ischemic preconditioning (RIPC), that is, cycles of ischemia/reperfusion in an organ remote from the heart before sustained myocardial ischemia/reperfusion, was confirmed in all species so far, including humans. To identify myocardial signal transduction of cardioprotection by RIPC. Anesthetized pigs were subjected to RIPC (4×5/5 minutes hindlimb ischemia/reperfusion) or placebo (PLA) before 60/180 minutes coronary occlusion/reperfusion. Phosphorylation of protein kinase B, extracellular signal-regulated kinase 1/2 (reperfusion injury salvage kinase [RISK] pathway), and signal transducer and activator of transcription 3 (survival activating factor enhancement [SAFE] pathway) in the area at risk was determined by Western blot. Wortmannin/U0126 or AG490 was used for pharmacological RISK or SAFE blockade, respectively. Plasma sampled after RIPC or PLA, respectively, was transferred to isolated bioassay rat hearts subjected to 30/120 minutes global ischemia/reperfusion. RIPC reduced infarct size in pigs to 16±11% versus 43±11% in PLA (% area at risk; mean±SD; P<0.05). RIPC increased the phosphorylation of signal transducer and activator of transcription 3 at early reperfusion, and AG490 abolished the protection, whereas RISK blockade did not. Signal transducer and activator of transcription 5 phosphorylation was decreased at early reperfusion in both RIPC and PLA. In isolated rat hearts, pig plasma taken after RIPC reduced infarct size (25±5% of ventricular mass versus 38±5% in PLA; P<0.05) and activated both RISK and SAFE. RISK or SAFE blockade abrogated this protection. Cardioprotection by RIPC in pigs causally involves activation of signal transducer and activator of transcription 3