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Sample records for acutely reperfused myocardial

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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)

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. [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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  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. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. [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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  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. 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.

  4. 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

  5. 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

  6. 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.

  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. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. [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.).

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

    2017-02-03

    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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. [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.

  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. 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

  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. 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.

  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. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Cardioprotective Effect of Electroacupuncture Pretreatment on Myocardial Ischemia/Reperfusion Injury via Antiapoptotic Signaling

    PubMed Central

    Lu, Sheng-feng; Huang, Yan; Wang, Ning; Shen, Wei-xing; Fu, Shu-ping; Li, Qian; Yu, Mei-ling; Liu, Wan-xin; Chen, Xia; Jing, Xin-yue; Zhu, Bing-mei

    2016-01-01

    Objectives. Our previous study has used RNA-seq technology to show that apoptotic molecules were involved in the myocardial protection of electroacupuncture pretreatment (EAP) on the ischemia/reperfusion (I/R) animal model. Therefore, this study was designed to investigate how EAP protects myocardium against myocardial I/R injury through antiapoptotic mechanism. Methods. By using rats with myocardial I/R, we ligated the left anterior descending artery (LAD) for 30 minutes followed by 4 hr of reperfusion after EAP at the Neiguan (PC6) acupoint for 12 days; we employed arrhythmia scores, serum myocardial enzymes, and cardiac troponin T (cTnT) to evaluate the cardioprotective effect. Heart tissues were harvested for western blot analyses for the expressions of pro- and antiapoptotic signaling molecules. Results. Our preliminary findings showed that EAP increased the survival of the animals along with declined arrhythmia scores and decreased CK, LDH, CK-Mb, and cTnT levels. Further analyses with the heart tissues detected reduced myocardial fiber damage, decreased number of apoptotic cells and the protein expressions of Cyt c and cleaved caspase 3, and the elevated level of Endo G and AIF after EAP intervention. At the same time, the protein expressions of antiapoptotic molecules, including Xiap, BclxL, and Bcl2, were obviously increased. Conclusions. The present study suggested that EAP protected the myocardium from I/R injury at least partially through the activation of endogenous antiapoptotic signaling. PMID:27313648

  13. 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.

  14. [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.

  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. 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.

  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. [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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  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. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. Total flavonoid extract from Coreopsis tinctoria Nutt. protects rats against myocardial ischemia/reperfusion injury

    PubMed Central

    Zhang, Ya; Yuan, Changsheng; Fang, He; Li, Jia; Su, Shanshan; Chen, Wen

    2016-01-01

    Objective(s): This study aimed to evaluate the protective effects of total flavonoid extract from Coreopsis tinctoria Nutt. (CTF) against myocardial ischemia/reperfusion injury (MIRI) using an isolated Langendorff rat heart model. Materials and Methods: Left ventricular developed pressure (LVDP) and the maximum rate of rise and fall of LV pressure (±dp/dtmax) were recorded. Cardiac injury was assessed by analyzing lactate dehydrogenase (LDH) and creatine kinase (CK) released in the coronary effluent. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels were determined. Myocardial inflammation was assessed by monitoring tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), and interleukin-6 (IL-6) levels. Myocardial infarct size was estimated. Cell morphology was assessed by 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin (HE) staining. Cardiomyocyte apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Results: Pretreatment with CTF significantly increased the heart rate and increased LVDP, as well as SOD and GSH-Px levels. In addition, CTF pretreatment decreased the TUNEL-positive cell ratio, infarct size, and levels of CK, LDH, MDA, TNF-α, CRP, IL-6, and IL-8. Conclusion: These results suggest that CTF exerts cardio-protective effects against MIRI via anti-oxidant, anti-inflammatory, and anti-apoptotic activities. PMID:27803790

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  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. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  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. 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

  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. 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.

  11. 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

  12. 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.

  13. [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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. [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.

  13. Low molecular weight heparin for treatment of acute myocardial infarction (FAMI): Fragmin (dalteparin sodium) in acute myocardial infarction.

    PubMed

    Kakkar, V V; Iyengar, S S; De Lorenzo, F; Hargreaves, J R; Kadziola, Z A

    2000-01-01

    The benefit of using subcutaneous low molecular weight heparin for the treatment of acute myocardial infarction is not known. The aim of this study was to determine the efficacy of a low molecular weight heparin (dalteparin sodium) for the treatment of acute myocardial infarction in patients not treated with thrombolytic therapy. Twenty-nine cardiological centres from leading hospitals in India participated in this prospective, multicentre, double-blind, placebo-controlled study in two phases which included 1128 patients with acute myocardial infarction. In the acute phase (between day 1 and 3 of admission) all the patients received a weight-adjusted dose of subcutaneous dalteparin (120 IU/kg twice daily). In the second, double-blind phase of acute myocardial infarction, patients were randomised to receive a fixed dose of dalteparin (7,500 IU) or an identical placebo injection for 30 days. A composite primary endpoint of death, reinfarction, recurrence of angina and emergency revascularisation was used. All the 1128 patients with acute myocardial infarction were included in the trial. In the acute phase, the composite primary endpoint was observed in 58 (5.1%) patients. Of 1037 paients who were randomly assigned to receive a fixed dose of dalteparin (n=519) or placebo (n=518), the composite primary event rate was 6.7 percent and 7.0 percent, respectively (RR 0.97; 95% CI 0.62-1.52; p=0.90). To conclude, treatment with dalteparin administered subcutaneously in a weight-adjusted dose of 120 IU/kg twice daily resulted in a lower than expected mortality during the acute phase of myocardial infarction. A lower fixed once daily dose of 7,500 IU during the chronic phase did not confer additional protection.

  14. Relation between the kinetics of thallium-201 in myocardial scintigraphy and myocardial metabolism in patients with acute myocardial infarction

    PubMed Central

    Yamagishi, H; Akioka, K; Takagi, M; Tanaka, A; Takeuchi, K; Yoshikawa, J; Ochi, H

    1998-01-01

    Objective—To investigate the relations between myocardial metabolism and the kinetics of thallium-201 in myocardial scintigraphy.
Methods—46 patients within six weeks after the onset of acute myocardial infarction underwent resting myocardial dual isotope, single acquisition, single photon emission computed tomography (SPECT) using radioiodinated 15-iodophenyl 3-methyl pentadecaenoic acid (BMIPP) and thallium-201, exercise thallium-201 SPECT, and positron emission tomography (PET) using nitrogen-13 ammonia (NH3) and [F18]fluorodeoxyglucose (FDG) under fasting conditions. The left ventricle was divided into nine segments, and the severity of defects was assessed visually.
Results—In the resting SPECT, less BMIPP uptake than thallium-201 uptake was observed in all of 40 segments with reverse redistribution of thallium-201, and in 21 of 88 segments with a fixed defect of thallium-201 (p < 0.0001); and more FDG uptake than NH3 uptake (NH3-FDG mismatch) was observed in 35 of 40 segments with reverse redistribution and in 38 of 88 segments with fixed defect (p < 0.0001). Less BMIPP uptake in the resting SPECT was observed in 49 of 54 segments with slow stress redistribution in exercise SPECT, and in nine of 17 segments with rapid stress redistribution (p < 0.0005); NH3-FDG mismatch was observed in 42 of 54 segments with slow stress redistribution and in five of 17 segments with rapid stress redistribution (p < 0.0005).
Conclusions—Thallium-201 myocardial scintigraphy provides information about not only myocardial perfusion and viability but also about myocardial metabolism in patients with acute myocardial infarction.

 Keywords: thallium-201 SPECT;  BMIPP SPECT;  FDG PET;  myocardial infarction;  redistribution PMID:9764055

  15. 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

  16. 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

  17. 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.

  18. Activation of SHH signaling pathway promotes vasculogenesis in post-myocardial ischemic-reperfusion injury

    PubMed Central

    Guo, Wei; Yi, Xin; Ren, Faxin; Liu, Liwen; Wu, Suning; Yang, Jun

    2015-01-01

    This study aimed to investigate the potential roles of sonic Hedgehog (SHH) expression in vasculogenesis in post-myocardial ischemic-reperfusion injury (MIRI) and its underlying mechanism. Cardiac microvascular endothelial cells (CMECs) isolated from the SD rat hearts tissues were used to construct the MIRI model. mRNA level of SHH in control cells and MIRI cells was detected using RT-PCR analysis. Furthermore, effects of SHH expression on CMECs viability and apoptosis were analyzed using MTT assay and Annexin-V-FITC kit respectively. Moreover, effects of SHH expression on the pathway signal proteins expression was analyzed using ELISA and western blotting. mRNA level of SHH was significantly decreased compared to the controls (P<0.05). Besides, CMECs viability was significantly increased while cell apoptosis was decreased by SHH application compared with the controls (P<0.05). Vasculogenesis-related factors including VEGF, FGF and Ang were significantly increased by SHH application, as well as the SHH signal proteins including Patch-1, Gli1, Gli2 and SMO (P<0.05). However, these effects of SHH application on biological factors levels were reversed by the SHH inhibitor application. This study suggested that SHH over expression may play a pivotal contribute role in vasculogenesis through activating the SHH signals in post-MIRI. PMID:26722433

  19. 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

  20. Amphetamine Containing Dietary Supplements and Acute Myocardial Infarction

    PubMed Central

    Hritani, Abdulwahab; Antoun, Patrick

    2016-01-01

    Weight loss is one of the most researched and marketed topics in American society. Dietary regimens, medications that claim to boost the metabolism, and the constant pressure to fit into society all play a role in our patient's choices regarding new dietary products. One of the products that are well known to suppress appetite and cause weight loss is amphetamines. While these medications suppress appetite, most people are not aware of the detrimental side effects of amphetamines, including hypertension, tachycardia, arrhythmias, and in certain instances acute myocardial infarction. Here we present the uncommon entity of an acute myocardial infarction due to chronic use of an amphetamine containing dietary supplement in conjunction with an exercise regimen. Our case brings to light further awareness regarding use of amphetamines. Clinicians should have a high index of suspicion of use of these substances when young patients with no risk factors for coronary artery disease present with acute arrhythmias, heart failure, and myocardial infarctions. PMID:27516911

  1. [Cardiogenic shock in acute myocardial infarct. Its coronary angioplasty treatment].

    PubMed

    Fernández Valadez, E; García y Otero, J M; Escobar, G P; Frutos Rangel, E; Zúñiga Sedano, J; García García, R; Verduzco Bazavilvazo, S; López Aranda, J; López Ruiz, J

    1993-01-01

    Ventricular dysfunction is the most common cause of in-hospital death in patients with acute myocardial infarction. When cardiogenic shock is manifested the mortality is very high. Seven patients with cardiogenic shock complicating acute myocardial infarction were treated with emergency coronary angioplasty. Four patients required cardiopulmonary resuscitation (CPR), 2 intraaortic balloon pump support and one femoro-femoral bypass pump support during the coronary angioplasty. The angiography success rate was 86%. Two patients died, one in the catheterization laboratory and the other one 24 hours later. The hospital mortality was 29%. Of the patients who survived 4 are in functional class I and one in functional class II (NYHA). Coronary angioplasty therapy in patients with cardiogenic shock complicating acute myocardial infarction plays a decisive role in the reduction of mortality.

  2. 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.

  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. 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.

  5. 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

  6. Computational modeling of acute myocardial infarction

    PubMed Central

    Sáez, P.; Kuhl, E.

    2015-01-01

    Myocardial infarction, commonly known as heart attack, is caused by reduced blood supply and damages the heart muscle because of a lack of oxygen. Myocardial infarction initiates a cascade of biochemical and mechanical events. In the early stages, cardiomyocytes death, wall thinning, collagen degradation, and ventricular dilation are the immediate consequences of myocardial infarction. In the later stages, collagenous scar formation in the infarcted zone and hypertrophy of the non-infarcted zone are auto-regulatory mechanisms to partly correct for these events. Here we propose a computational model for the short-term adaptation after myocardial infarction using the continuum theory of multiplicative growth. Our model captures the effects of cell death initiating wall thinning, and collagen degradation initiating ventricular dilation. Our simulations agree well with clinical observations in early myocardial infarction. They represent a first step towards simulating the progression of myocardial infarction with the ultimate goal to predict the propensity toward heart failure as a function of infarct intensity, location, and size. PMID:26583449

  7. Computational modeling of acute myocardial infarction.

    PubMed

    Sáez, P; Kuhl, E

    2016-01-01

    Myocardial infarction, commonly known as heart attack, is caused by reduced blood supply and damages the heart muscle because of a lack of oxygen. Myocardial infarction initiates a cascade of biochemical and mechanical events. In the early stages, cardiomyocytes death, wall thinning, collagen degradation, and ventricular dilation are the immediate consequences of myocardial infarction. In the later stages, collagenous scar formation in the infarcted zone and hypertrophy of the non-infarcted zone are auto-regulatory mechanisms to partly correct for these events. Here we propose a computational model for the short-term adaptation after myocardial infarction using the continuum theory of multiplicative growth. Our model captures the effects of cell death initiating wall thinning, and collagen degradation initiating ventricular dilation. Our simulations agree well with clinical observations in early myocardial infarction. They represent a first step toward simulating the progression of myocardial infarction with the ultimate goal to predict the propensity toward heart failure as a function of infarct intensity, location, and size.

  8. Astragaloside IV enhances cardioprotection of remote ischemic conditioning after acute myocardial infarction in rats

    PubMed Central

    Cheng, Songyi; Yu, Peng; Yang, Li; Shi, Haibo; He, Anxia; Chen, Hanyu; Han, Jie; Xie, Liang; Chen, Jiandong; Chen, Xiaohu

    2016-01-01

    Background: Remote ischemic conditioning (RIC) has been shown to be a practical method for protecting the heart from ischemic/reperfusion (I/R) injury. In the present study, we investigated whether or not the combination of RIC and Astragaloside IV (AS-IV) could improve cardioprotection against acute myocardial infarction (AMI)-induced heart failure (HF) when compared with individual treatments. Material and Methods: A rat model of AMI was established via permanent ligation of the left anterior descending coronary artery (LAD). Postoperatively, the rats were randomly grouped into a sham group (n=10), a model group (n=15), an AS-IV alone group (n=15), an RIC alone group (n=15) and a combined treatment group (AS-IV+RIC; n=15). All treatments were administered for 2 weeks. Results: After treatment for 2 weeks, the survival rate was improved, the cardiac function was preserved and the infarcted size was limited in AS-IV alone and RIC alone treatment groups compared to the model group, whereas the combined treatment yielded the most optimal protective effects. Additional studies suggested that AS-IV enhanced the cardioprotective effects of RIC by alleviating myocardial fibrosis, suppressing inflammation, attenuating apoptosis and ameliorating impairment of the myocardial ultrastructural. Conclusion: AS-IV enhances the cardioprotective effects of RIC against AMI-induced HF and ventricular remodeling, which represents a potential therapeutic approach for preserving cardiac function and improving the prognosis of AMI. PMID:27904669

  9. Risk stratification after acute myocardial infarction: which studies are best?

    PubMed

    Figueredo, V M

    1996-04-01

    The prognosis for a patient who has survived an acute myocardial infarction depends on three general prognostic factors: (1) residual left ventricular function, (2) remaining viable myocardium at risk (residual ischemia), and (3) presence of substrate for the development of malignant arrhythmias. Multiple clinical and historical factors predict the presence of one or more of these prognostic indicators. Electrocardiographic exercise treadmill testing needs to be done in all patients with uncomplicated infarctions. Guidelines of the American College of Cardiology/American Heart Association Task Force are recommended for risk stratification in most patients after acute myocardial infarction.

  10. ST-elevation acute myocardial infarction in pregnancy: 2016 update.

    PubMed

    Ismail, Sahar; Wong, Cynthia; Rajan, Priya; Vidovich, Mladen I

    2017-02-13

    Acute myocardial infarction (AMI) during pregnancy or the early postpartum period is rare, but can be devastating for both the mother and the fetus. There have been major advances in the diagnosis and treatment of acute coronary syndromes in the general population, but there is little consensus on the approach to diagnosis and treatment of pregnant women. This article reviews the literature relating to the pathophysiology of AMI in pregnant patients and the challenges in diagnosis and treatment of ST-elevation myocardial infarction (STEMI) in this unique population. From a cardiologist, maternal-fetal medicine specialist, and anesthesiologist's perspective, we provide recommendations for the diagnosis and management of STEMI occurring during pregnancy.

  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. 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

  13. 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.

  14. Biochemical assessment of acute myocardial ischaemia.

    PubMed Central

    Perez-Cárceles, M D; Osuna, E; Vieira, D N; Martínez, A; Luna, A

    1995-01-01

    AIMS--To evaluate the efficacy of biochemical parameters in different fluids in the diagnosis of myocardial infarction of different causes, analysed after death. METHODS--The myoglobin concentration and total creatine kinase (CK) and creatine kinase MB isoenzyme (CK-MB) activities were measured in serum, pericardial fluid, and vitreous humour from seven diagnostic groups of cadavers classified according to the severity of myocardial ischaemia and cause of death. Lactate dehydrogenase (LDH) and myosin were measured only in serum and pericardial fluid, and cathepsin D only in pericardial fluid. Routine haematoxylin and eosin and acridine orange staining were used for microscopy studies of heart tissue. RESULTS--In pericardial fluid there were substantial differences between the different groups with respect to CK, CK-MB, and LDH activities and myosin concentrations. The highest values were found in cases with morphological evidence of myocardial ischaemia. CONCLUSIONS--Biochemical parameters, which reach the pericardial fluid via passive diffusion and ultrafiltration due to a pressure gradient, were thus detectable in this fluid earlier than in serum in cases with myocardial ischaemia. These biochemical parameters may be of use for ruling out myocardial ischaemia in those controversial cases in which reliable morphological findings are lacking. PMID:7745110

  15. 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

  16. Targeting TRAF3IP2 by Genetic and Interventional Approaches Inhibits Ischemia/Reperfusion-induced Myocardial Injury and Adverse Remodeling.

    PubMed

    Erikson, John M; Valente, Anthony J; Mummidi, Srinivas; Kandikattu, Hemanth Kumar; DeMarco, Vincent G; Bender, Shawn B; Fay, William P; Siebenlist, Ulrich; Chandrasekar, Bysani

    2017-02-10

    Re-establishing blood supply is the primary goal for reducing myocardial injury in subjects with ischemic heart disease. Paradoxically, reperfusion results in nitroxidative stress and a marked inflammatory response in the heart. TRAF3IP2 (TRAF3 Interacting Protein 2; previously known as CIKS or Act1) is an oxidative stress-responsive cytoplasmic adapter molecule that is an upstream regulator of both IκB kinase (IKK) and c-Jun N-terminal kinase (JNK), and an important mediator of autoimmune and inflammatory responses. Here we investigated the role of TRAF3IP2 in ischemia/reperfusion (I/R)-induced nitroxidative stress, inflammation, myocardial dysfunction, injury, and adverse remodeling. Our data show that I/R up-regulates TRAF3IP2 expression in the heart, and its gene deletion, in a conditional cardiomyocyte-specific manner, significantly attenuates I/R-induced nitroxidative stress, IKK/NF-κB and JNK/AP-1 activation, inflammatory cytokine, chemokine, and adhesion molecule expression, immune cell infiltration, myocardial injury, and contractile dysfunction. Furthermore, Traf3ip2 gene deletion blunts adverse remodeling 12 weeks post-I/R, as evidenced by reduced hypertrophy, fibrosis, and contractile dysfunction. Supporting the genetic approach, an interventional approach using ultrasound-targeted microbubble destruction-mediated delivery of phosphorothioated TRAF3IP2 antisense oligonucleotides into the LV in a clinically relevant time frame significantly inhibits TRAF3IP2 expression and myocardial injury in wild type mice post-I/R. Furthermore, ameliorating myocardial damage by targeting TRAF3IP2 appears to be more effective to inhibiting its downstream signaling intermediates NF-κB and JNK. Therefore, TRAF3IP2 could be a potential therapeutic target in ischemic heart disease.

  17. Safety and feasibility of prehospital thrombolysis in combination with active rescue PCI strategy for acute ST-elevation myocardial infarction

    PubMed Central

    Firanescu, C.; Wilbers, R.; Meeder, J.G.

    2005-01-01

    Background/Objectives The purpose of this observational study was to provide an impression of the outcomes of prehospital thrombolysis in combination with an active coronary angioplasty intervention (PCI) strategy for acute ST-elevation myocardial infarction. Methods In a group of 151 consecutive patients the following parameters were measured: time delay, percentage of reperfusion, reocclusion, stroke, death, need for PCI and the number of protocol violations. Results The diagnosis by the ambulance paramedics was made in 8±6 minutes, followed by thrombolysis in 13±7 minutes (median±SD). In 2% (3) of the patients the thrombolytic agent was erroneously administered without complications. The elapsed time from onset of symptoms to treatment was a median of 112±77 minutes. Five percent (7) of the patients died in the first 30 days and 2% (3) suffered an intracerebral haemorrhage. Reperfusion was documented in 76% (112) of the patients, from which 18% (20) reoccluded in the following 24 hours. In patients where reperfusion was not established or reocclusion occurred, patients underwent rescue/facilitated PCI: in total 37% (55 patients). After three months 9% (13) of the patients had severly impaired (EF <40%) left ventricular function. Conclusion In our region, we successfully implemented the prehospital thrombolysis system achieving a competitive call-to-needle time and reperfusion rate. The percentage of patients who violated the protocol, suffered an intracerebral haemorrhage, died and/or had severely impaired left ventricular function was acceptable. ImagesFigure 1 PMID:25696516

  18. Helicobacter pylori seropositivity in subjects with acute myocardial infarction.

    PubMed Central

    Rathbone, B.; Martin, D.; Stephens, J.; Thompson, J. R.; Samani, N. J.

    1996-01-01

    OBJECTIVE: To determine whether Helicobacter pylori infection increases the risk of myocardial infarction. DESIGN: Case-control study. SETTING: University teaching hospital. METHODS: Serological evidence of H pylori infection was determined in 342 consecutive patients with acute myocardial infarction admitted into the coronary care unit and in 236 population-based controls recruited from visitors to patients on medical and surgical wards. RESULTS: 206/342 (60.2%) of cases were H pylori positive compared with 132/236 (55.9%) of controls (P = 0.30). Age and sex stratified odds ratio for myocardial infarction associated with H pylori seropositivity was 1.05 (95% CI 0.7 to 1.53, P = 0.87) and this remained non-significant (P = 0.46) when other risk factors for ischaemic heart disease were taken into account using logistic regression analysis. H pylori seropositivity was not associated with several coronary risk factors in either cases or controls. CONCLUSION: No increase was found in H pylori seropositivity in subjects with acute myocardial infarction. This suggests that previous H pylori infection is not a major risk factor for acute myocardial infarction. Images PMID:8983674

  19. Reduced myocardial blood flow in acute and chronic digitalization.

    PubMed

    Steiness, E; Bille-Brahe, N E; Hansen, J F; Lomholt, N; Ring-Larsen, H

    1978-07-01

    The myocardial blood flow was measured by the 133Xenon disappearance curve from the left ventricular wall following an injection of 133Xenon in the left coronary artery in 8 dogs without digoxin pretreatment and in 8 chronically digitalized dogs. The myocardial blood flow was significantly less (30%) in the digitalized dogs than in the dogs without pretreatment. In the digitalized dogs as well as in those without pretreatment an intravenous injection of digoxin resulted in a further significant decrease of the myocardial blood flow of about 20% and a significant increase of the coronary vascular resistance. The reduced myocardial blood flow both during acute and chronic digitalization is beleived to be of clinical importance.

  20. Activation of NOD1 by DAP contributes to myocardial ischemia/reperfusion injury via multiple signaling pathways.

    PubMed

    Yang, Hui; Li, Nan; Song, Li-Na; Wang, Lei; Tian, Cui; Tang, Chao-Shu; Du, Jie; Li, Hui-Hua; Yu, Xiao-Hong; Wang, Hong-Xia

    2015-04-01

    NOD1 is a member of nucleotide-binding oligomerization domain-like receptors family that participates in many inflammatory processes. Previous studies demonstrated that NOD1 plays an important role in inflammatory cardiovascular diseases. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. The present study investigate whether NOD1 is involved in the pathogenesis of mouse myocardial I/R injury and the underlying mechanisms. Administration of NOD1 ligand (DAP) significantly enhanced myocardial I/R injury, as demonstrated by increased infarct size, the number of TUNEL-positive nuclei, caspase-3 activity, the infiltration of Mac-2- and IL-6-positive cells as compared with untreated heart or cardiomyocytes after I/R injury. In contrast, knockdown of NOD1 by siRNA markedly attenuated mimetic I/R induced cardiomyocyte apoptosis in vitro, indicating that NOD1 enhanced myocardial I/R injury partially through direct heart effects. These effects were partially associated with activation of JNK, p38 MAPK and NF-κB signaling pathways. Taken together, these results provide the first evidence that activation of intracellular sensor NOD1 enhances myocardial I/R injury and may provide novel therapeutic target for ameliorating the ischemic heart diseases.

  1. Clinical, functional, and angiographic distinctions between Q wave and non-Q wave myocardial infarction: evidence of spontaneous reperfusion and implications for intervention trials

    SciTech Connect

    Gibson, R.S.

    1987-06-01

    We prospectively evaluated 241 consecutive patients with creatine kinase (MB fraction)-confirmed acute myocardial infarction with predischarge quantitative thallium-201 scintigraphy, coronary angiography, radionuclide ventriculography, and 24 hr Holter monitoring. Based on serial electrocardiograms, 154 patients had Q wave (QMI) and 87 had non-Q wave (NQMI) infarction. Despite less myocardial necrosis and better left ventricular function, the NQMI group had the same long-term survival as the QMI group. During 27 months of follow-up, patients with NQMI experienced more reinfarctions (p = .009), had a higher rate of unstable angina pectoris requiring rehospitalization (p = .034), and had a greater likelihood of subsequent bypass surgery or angioplasty (p = .018). Based on our thallium scintigraphic data, the greater clinical instability after NQMI appeared to be related to the presence of a larger residual mass of viable but jeopardized myocardium within the perfusion zone of the infarct-related vessel. Our results also indicate that the pathogenesis of NQMI may involve early spontaneous reperfusion and that patients with NQMI can experience sudden death despite well-preserved left ventricular function.

  2. Acute myocardial infarction in a young man using anabolic steroids.

    PubMed

    Wysoczanski, Mariusz; Rachko, Maurice; Bergmann, Steven R

    2008-01-01

    Anabolic-androgenic steroids are used worldwide to help athletes gain muscle mass and strength. Their use and abuse is associated with numerous side effects, including acute myocardial infarction (MI). We report a case of MI in a young 31-year-old bodybuilder. Because of the serious cardiovascular complications of anabolic steroids, physicians should be aware of their abuse and consequences.

  3. [Acute myocardial infarction in a 5-year-old boy].

    PubMed

    Romero Ibarra, C; Bueno Campaña, M; Barriuso Lapresa, L M; de Miguel Medina, C; Maraví Poma, E

    1996-11-01

    We present the case of a child five and half years-old that died suddenly due to an acute myocardial infarction. The anatomopathological study showed a total obstruction of the left coronary ostium by mixoide dysplasia of the aortic valve. We revise the literature and briefly expose the more frequent causes of infarction in infancy.

  4. Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction

    PubMed Central

    Joshi, Nikhil V; Toor, Iqbal; Shah, Anoop S V; Carruthers, Kathryn; Vesey, Alex T; Alam, Shirjel R; Sills, Andrew; Hoo, Teng Y; Melville, Adam J; Langlands, Sarah P; Jenkins, William S A; Uren, Neal G; Mills, Nicholas L; Fletcher, Alison M; van Beek, Edwin J R; Rudd, James H F; Fox, Keith A A; Dweck, Marc R; Newby, David E

    2015-01-01

    Background Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans. Methods and Results Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non–ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI. Conclusions The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization

  5. Bnip3 functions as a mitochondrial sensor of oxidative stress during myocardial ischemia and reperfusion.

    PubMed

    Kubli, Dieter A; Quinsay, Melissa N; Huang, Chengqun; Lee, Youngil; Gustafsson, Asa B

    2008-11-01

    Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) is a member of the Bcl-2 homology domain 3-only subfamily of proapoptotic Bcl-2 proteins and is associated with cell death in the myocardium. In this study, we investigated the potential mechanism(s) by which Bnip3 activity is regulated. We found that Bnip3 forms a DTT-sensitive homodimer that increased after myocardial ischemia-reperfusion (I/R). The presence of the antioxidant N-acetylcysteine reduced I/R-induced homodimerization of Bnip3. Overexpression of Bnip3 in cells revealed that most of exogenous Bnip3 exists as a DTT-sensitive homodimer that correlated with increased cell death. In contrast, endogenous Bnip3 existed mainly as a monomer under normal conditions in the heart. Screening of the Bnip3 protein sequence revealed a single conserved cysteine residue at position 64. Mutation of this cysteine to alanine (Bnip3C64A) or deletion of the NH2-terminus (amino acids 1-64) resulted in reduced cell death activity of Bnip3. Moreover, mutation of a histidine residue in the COOH-terminal transmembrane domain to alanine (Bnip3H173A) almost completely inhibited the cell death activity of Bnip3. Bnip3C64A had a reduced ability to interact with Bnip3, whereas Bnip3H173A was completely unable to interact with Bnip3, suggesting that homodimerization is important for Bnip3 function. A consequence of I/R is the production of reactive oxygen species and oxidation of proteins, which promotes the formation of disulfide bonds between proteins. Thus, these experiments suggest that Bnip3 functions as a redox sensor where increased oxidative stress induces homodimerization and activation of Bnip3 via cooperation of the NH2-terminal cysteine residue and the COOH-terminal transmembrane domain.

  6. A Review of Interventions and System Changes to Improve Time to Reperfusion for ST-Segment Elevation Myocardial Infarction

    PubMed Central

    McDermott, Kelly A.; Helfrich, Christian D.; Rumsfeld, John S.; Ho, P. Michael; Fihn, Stephan D.

    2008-01-01

    Objective Identify and describe interventions to reduce time to reperfusion for patients with ST-segment elevation myocardial infarction (STEMI). Data Source Key word searches of five research databases: MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Web of Science, and Cochrane Clinical Trials Registry. Interventions We included controlled and uncontrolled studies of interventions to reduce time to reperfusion. One researcher reviewed abstracts and 2 reviewed full text articles. Articles were subsequently abstracted into structured data tables, which included study design, setting, intervention, and outcome variables. We inductively developed intervention categories from the articles. A second researcher reviewed data abstraction for accuracy. Measurements and Main Results We identified 666 articles, 42 of which met inclusion criteria. We identified 11 intervention categories and classified them as either process specific (e.g., emergency department administration of thrombolytic therapy, activation of the catheterization laboratory by emergency department personnel) or system level (e.g., continuous quality improvement, critical pathways). A majority of studies (59%) were single-site pre/post design, and nearly half (47%) had sample sizes less than 100 patients. Thirty-two studies (76%) reported significantly lower door to reperfusion times associated with an intervention, 12 (29%) of which met or exceeded guideline recommended times. Relative decreases in times to reperfusion ranged from 15 to 82% for door to needle and 13–64% for door to balloon. Conclusions We identified an array of process and system-based quality improvement interventions associated with significant improvements in door to reperfusion time. However, weak study designs and inadequate information about implementation limit the usefulness of this literature. Electronic supplementary materials The online version of this article (doi:10.1007/s11606

  7. Acute T3 treatment protects the heart against ischemia-reperfusion injury via TRα1 receptor.

    PubMed

    Pantos, Constantinos; Mourouzis, Iordanis; Saranteas, Theodosios; Brozou, Vassiliki; Galanopoulos, Georgios; Kostopanagiotou, Georgia; Cokkinos, Dennis V

    2011-07-01

    We have previously shown that acute thyroid hormone treatment could limit reperfusion injury and increase post-ischemic recovery of function. In the present study, we further explore potential initiating mechanisms of this response. Thus, isolated rat hearts were subjected to 30 min zero-flow global ischemia (I) followed by 60-min reperfusion (R). Reperfusion injury was assessed by post-ischemic recovery of left ventricular developed pressure (LVDP%) and LDH release. T3 at a dose of 60 nM which had no effect on contractile function of non-ischemic myocardium, significantly increased LVDP% [48% (2.9) vs. 30.2% (3.3) for untreated group, P < 0.05] and reduced LDH release [8.3 (0.3) vs. 10 (0.42) for untreated group, P < 0.05] when administered at R. T4 (60 and 400 nM) had no effect on contractile function either in non-ischemic or ischemic myocardium. Administration of debutyl-dronedarone (DBD), a TRα1 antagonist abolished the T3-limiting effect on reperfusion injury: Thus, co-administration of T3 and DBD resulted in significantly lower LVDP%, [23% (4.7) vs. 48% (2.9) for T3 group, P < 0.05] and higher LDH release [9.9 (0.3) vs. 8.3 (0.3), for T3 group, P < 0.05]. In conclusion, acute T3 and not T4 treatment will be able to protect against reperfusion injury. T3 can exert this beneficial effect on ischemic myocardium at a dose that has no effects on non-ischemic myocardium. Acute T3-limiting effect on reperfusion injury is mediated, at least in part, via TRα1 receptor.

  8. Inhibition of Angiotensin-II Production Increases Susceptibility to Acute Ischemia/Reperfusion Arrhythmia

    PubMed Central

    Taskin, Eylem; Tuncer, Kadir Ali; Guven, Celal; Kaya, Salih Tunc; Dursun, Nurcan

    2016-01-01

    Background Myocardial ischemia and reperfusion lead to impairment of electrolyte balance and, eventually, lethal arrhythmias. The aim of this study was to investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II) production on heart tissue with ischemia-reperfusion damage, arrhythmia, and oxidative stress. Material/Methods Rats were divided into 4 groups: only ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The drugs were given by gavage 30 min before anesthesia. Blood pressure and electrocardiography (ECG) were recorded during MI/R procedures. The heart tissue and plasma was kept so as to evaluate the total oxidant (TOS), antioxidant status (TAS), and creatine kinase-MB (CK-MB). Results Creatine kinase-MB was not different among the groups. Although TAS was not affected by inhibition of Ang-II production, TOS was significantly lower in the CAP and/or AL groups than in the MI/R group. Furthermore, oxidative stress index was significantly attenuated in the CAP and/or AL groups. Captopril significantly increased the duration of VT during ischemia; however, it did not have any effect on the incidence of arrhythmias. During reperfusion periods, aliskiren and its combinations with captopril significantly reduced the incidence of other types of arrhythmias. Captopril alone had no effect on the incidence of arrhythmias, but significantly increased arrhythmias score and durations of arrhythmias during reperfusion. MAP and heart rate did not show changes in any groups during ischemic and reperfusion periods. Conclusions Angiotensin-II production appears to be associated with elevated levels of reactive oxygen species, but Ang-II inhibitions increases arrhythmia, mainly by initiating ventricular ectopic beats. PMID:27889788

  9. Acute Effects of Intracoronary Tirofiban on No-Reflow Phenomena in Patients With ST-Segment Elevated Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

    PubMed

    Akpek, Mahmut; Sahin, Omer; Sarli, Bahadir; Baktir, Ahmet Oguz; Saglam, Hayrettin; Urkmez, Serkan; Ergin, Ali; Oguzhan, Abdurrahman; Arinc, Huseyin; Kaya, Mehmet G

    2015-07-01

    We evaluated the acute effect of intracoronary administration of tirofiban on no-reflow phenomenon in patients with ST-segment elevated myocardial infarction undergoing primary percutaneous coronary intervention. Consecutive patients (n = 162) were randomized into 2 groups based on whether intracoronary tirofiban was administered. After the administration of intracoronary tirofiban, thrombolysis in myocardial infarction (TIMI) flow grade significantly increased (P < .001) and successful reperfusion was achieved in 26 (32%) patients. In the placebo group, however, after the administration of intracoronary placebo the TIMI flow grade did not change (P = .070), and successful reperfusion was achieved only in 8 (10%) patients. In-hospital major adverse cardiac events (MACE) were significantly lower in the tirofiban group (36% vs 19%, P = .013). Intracoronary administration of tirofiban significantly improves TIMI flow grade and is associated with a lower in-hospital rate of MACE.

  10. Current trend of acute myocardial infarction in Korea (from the Korea Acute Myocardial Infarction Registry from 2006 to 2013).

    PubMed

    Kook, Hyun Yi; Jeong, Myung Ho; Oh, Sangeun; Yoo, Sung-Hee; Kim, Eun Jung; Ahn, Youngkeun; Kim, Ju Han; Chai, Leem Soon; Kim, Young Jo; Kim, Chong Jin; Chan Cho, Myeong

    2014-12-15

    Although the incidence of acute myocardial infarction (AMI) in Korea has been rapidly changed because of westernization of diet, lifestyle, and aging of the population, the recent trend of the myocardial infarction have not been reported by classification. We investigated recent trends in the incidence and mortality associated with the 2 major types of AMI. We reviewed 39,978 patients registered in the Korea Acute Myocardial Infarction Registry for either ST-segment elevation acute myocardial infarction (STEMI) or non-ST-segment elevation acute myocardial infarction (NSTEMI) from 2006 to 2013. When the rate for AMI were investigated according to each year, the incidence rates of STEMI decreased markedly from 60.5% in 2006 to 48.1% in 2013 (p <0.001). In contrast, a gradual increase in the incidence rates of NSTEMI was observed from 39.5% in 2006 to 51.9% in 2013 (p <0.001). As risk factors, hypertension, diabetes mellitus, and dyslipidemia were much more common in patients with NSTEMI than STEMI. Among medical treatments, the use of β blockers, angiotensin receptor blocker, and statin were increased from 2006 to 2013 in patients with STEMI and NSTEMI. Patients with STEMI and NSTEMI were more inclined to be increasingly treated by invasive treatments with percutaneous coronary intervention. In conclusion, this study demonstrated that the trend of myocardial infarction has been changed rapidly in the aspect of risk factors, ratio of STEMI versus NSTEMI, and therapeutic strategies during the recent 8 years in Korea.

  11. Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model.

    PubMed

    Kang, Pin-Fang; Wu, Wen-Juan; Tang, Yang; Xuan, Ling; Guan, Su-Dong; Tang, Bi; Zhang, Heng; Gao, Qin; Wang, Hong-Ju

    2016-01-01

    The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2) when diabetes mellitus (DM) rat heart was subjected to ischemia/reperfusion (I/R) intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH); cardiomyocyte in high glucose (HG) condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker), atractyloside (mitoPTP opener), and wortmannin (PI3K inhibitor) groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening.

  12. Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model

    PubMed Central

    Kang, Pin-Fang; Wu, Wen-Juan; Tang, Yang; Xuan, Ling; Guan, Su-Dong; Tang, Bi; Zhang, Heng

    2016-01-01

    The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2) when diabetes mellitus (DM) rat heart was subjected to ischemia/reperfusion (I/R) intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH); cardiomyocyte in high glucose (HG) condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker), atractyloside (mitoPTP opener), and wortmannin (PI3K inhibitor) groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening. PMID:27829984

  13. The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury

    PubMed Central

    2013-01-01

    Background MicroRNAs were enrolled in various cardiovascular disease especially ischemic heart diseases, but the microRNA changes during myocardial ischemia reperfusion injury underwent cardiopulmonary bypass are still unknown. This study screens the microRNA differences in CPB canines and evaluates the relationship of microRNAs with myocardial ischemia reperfusion injury. Methods 13 healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Left ventricular myocardial samples, blood samples and hemodynamic data were taken at different time points. We performed microRNAs microarray experiments upon the left ventricle myocardium tissue of canines before CPB and after reperfusion for 90 minutes by pooling 3 tissue samples together and used qRT-PCR for confirmation. Results Statistically significant difference was found in mir-499 level before CPB and after reperfusion (T1 vs. T4, p = 0.041). We further examined the mir-499 levels by using qRT-PCR in all 13 canines at 4 different time points (T1 vs. T4, p = 0.029). Mir-499 expression was negatively correlated with cardiac troponin T (cTnT) and creatine kinase- MB (CK-MB) levels of canines in all time points samples (r = 0.469, p < 0.001 and r = 0.273, p = 0.050 respectively). Moreover, higher mir-499 expression level was associated with higher dP/dtmax at 25 minutes and 90 minutes after reperfusion. Conclusion Myocardial ischemic reperfusion injury with cardiopulmonary bypass results in declining level of mir-499 expression in left ventricle myocardium of canines, suggesting mir-499 would be a potential therapeutic target in cardiac protection during open heart surgery. PMID:23800236

  14. Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

    PubMed Central

    Bukowczan, Jakub; Warzecha, Zygmunt; Ceranowicz, Piotr; Kuśnierz-Cabala, Beata; Tomaszewska, Romana

    2015-01-01

    Objective Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis. Aim The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion. Methods Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8nmol/kg/dose) was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula. Results Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food

  15. Effects of dexmedetomidine postconditioning on myocardial ischemia and the role of the PI3K/Akt-dependent signaling pathway in reperfusion injury

    PubMed Central

    CHENG, XIANG YANG; GU, XIAO YU; GAO, QIN; ZONG, QIAO FENG; LI, XIAO HONG; ZHANG, YE

    2016-01-01

    The present study aimed to determine whether post-ischemic treatment with dexmedetomidine (DEX) protected the heart against acute myocardial ischemia/reperfusion (I/R)-induced injury in rats. The phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)-dependent signaling pathway was also investigated. Male Sprague Dawley rats (n=64) were subjected to ligation of the left anterior descending artery (LAD), which produced ischemia for 25 min, followed by reperfusion. Following LAD ligation, rats were treated with DEX (5, 10 and 20 µg/kg) or underwent post-ischemic conditioning, which included three cycles of ischemic insult. In order to determine the role of the PI3K/Akt signaling pathway, wortmannin (Wort), a PI3K inhibitor, was used to treat a group of rats that had also been treated with DEX (20 µg/kg). Post-reperfusion, lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase isoenzymes (CK-MB), superoxide dismutase (SOD) and malondialdehyde (MDA) serum levels were measured using an ultraviolet spectrophotometer. The protein expression levels of phosphorylated (p)-Akt, Ser9-p-glycogen synthase kinase-3β (p-GSK-3β) and cleaved caspase-3 were detected in heart tissue by western blotting. The mRNA expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected using reverse transcription-polymerase chain reaction. At the end of the experiment, the hearts were removed and perfused in an isolated perfusion heart apparatus with Evans blue (1%) in order to determine the non-ischemic areas. The risk and infarct areas of the heart were not dyed. As expected, I/R induced myocardial infarction, as determined by the increased serum levels of cTnI, CK-MB and MDA, and the decreased levels of SOD. Post-ischemic treatment with DEX increased the expression levels of p-Akt and p-GSK-3β, whereas caspase-3 expression was reduced following DEX treatment compared with in the I/R group. Compared with the I/R group, the ratio of Bcl

  16. Holmium:YAG laser coronary angioplasty in acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Topaz, On; Luxenberg, Michael; Schumacher, Audrey

    1994-07-01

    Patients who sustain complicated acute myocardial infarction in whom thrombolytic agents either fail or are contraindicated often need mechanical revascularization other than PTCA. In 24 patients with acute infarction complicated by continuous chest pain and ischemia who either received lytics or with contraindication to lytics, a holmium:YAG laser (Eclipse Surgical Technologies, Palo Alto, CA) was utilized for thrombolysis and plaque ablation. Clinical success was achieved in 23/24 patients, with 23 patients (94%) surviving the acute infarction. Holmium:YAG laser is very effective and safe in thrombolysis and revascularization in this complicated clinical setting.

  17. EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction

    PubMed Central

    Cuadrado, Irene; Piedras, Maria Jose Garcia Miguel; Herruzo, Irene; Turpin, Maria del Carmen; Castejón, Borja; Reventun, Paula; Martin, Ana; Saura, Marta; Zamorano, Jose Luis; Zaragoza, Carlos

    2016-01-01

    Inhibition of extracellular matrix (ECM) degradation may represent a mechanism for cardiac protection against ischemia. Extracellular matrix metalloproteinase inducer (EMMPRIN) is highly expressed in response to acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including gelatinases MMP-2 and MMP-9. We targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles conjugated with the EMMPRIN binding peptide AP-9 (NAP9), or an AP-9 scrambled peptide as a negative control (NAPSC). We found that NAP9 binds to endogenous EMMPRIN in cultured HL1 myocytes and in mouse hearts subjected to ischemia/reperfusion (IR). Injection of NAP9 at the time of or one day after IR, was enough to reduce progression of myocardial cell death when compared to Control and NAPSC injected mice (infarct size in NAP9 injected mice: 32%±6.59 vs Control: 46%±9.04 or NAPSC injected mice: 48%±7.64). In the same way, cardiac parameters were recovered to almost healthy levels (LVEF NAP9 63% ± 7.24 vs Control 42% ± 4.74 or NAPSC 39% ± 6.44), whereas ECM degradation was also reduced as shown by inhibition of MMP-2 and MMP-9 activation. Cardiac magnetic resonance (CMR) scans have shown a signal enhancement in the left ventricle of NAP9 injected mice with respect to non-injected, and to mice injected with NAPSC. A positive correlation between CMR enhancement and Evans-Blue/TTC staining of infarct size was calculated (R:0.65). Taken together, these results point to EMMPRIN targeted nanoparticles as a new approach to the mitigation of ischemic/reperfusion injury. PMID:26941847

  18. Effects of antagonists for endothelin ET(A) and ET(B) receptors on coronary endothelial and myocardial function after ischemia-reperfusion in anesthetized goats.

    PubMed

    Climent, Belén; Fernández, Nuria; García-Villalón, Angel Luis; Monge, Luis; Sánchez, Ana; Diéguez, Godofredo

    2006-05-01

    To compare the effects of antagonists for endothelin ET(A) and ET(B) receptors on the action of ischemia-reperfusion on endothelial and myocardial function, 30 min of partial or total occlusion followed by 60 min of reperfusion of the left circumflex coronary artery was induced in anesthetized goats treated with intracoronary administration of saline (vehicle), BQ-123 (endothelin ET(A) receptors antagonist) or BQ-788 (endothelin ET(B) receptors antagonist). During reperfusion after partial occlusion, coronary vascular conductance and left ventricle dP/dt were decreased after saline or BQ-788, and they normalized after BQ-123. In these three groups of animals, the coronary effects of acetylcholine (3-100 ng) and sodium nitroprusside (1-10 microg) during reperfusion were as under control. During reperfusion after total occlusion, coronary vascular conductance and left ventricle dP/dt were decreased after saline, and they normalized after BQ-123 or BQ-788. In these three groups of animals, the coronary effects of acetylcholine but not those of sodium nitroprusside during reperfusion were decreased after saline, and they reversed after BQ-123 or BQ-788. Therefore, selective antagonists of endothelin ET(B) and ET(A) receptors may produce similar protection of coronary vasculature and myocardium against reperfusion after severe ischemia. Selective antagonists of endothelin ET(B) receptors, contrarily to those of endothelin ET(A) receptors, may be ineffective to protect coronary vasculature and myocardium against reperfusion after mild ischemia.

  19. In vivo gene transfection with heat shock protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat.

    PubMed Central

    Suzuki, K; Sawa, Y; Kaneda, Y; Ichikawa, H; Shirakura, R; Matsuda, H

    1997-01-01

    Heat shock protein 70 (HSP70) has been reported to be involved in the myocardial self-preservation system. To obtain the evidence that HSP70 plays a direct role in the protection from myocardial ischemia-reperfusion injury, rat hearts were transfected with human HSP70 gene by intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome containing human HSP70 gene. The control hearts were infused with HVJ-liposome without the HSP70 gene. The hearts from whole-body heat-stressed or nontreated rats were also examined. Western blot and immunohistochemical analysis showed that apparent overexpression of HSP70 occurred in the gene transfected hearts and that gene transfection might be more effective for HSP70 induction than heat stress. In Langendorff perfusion, better functional recovery as well as less creatine phosphokinase leakage after ischemia were obtained in the gene transfected hearts with HSP70 than in the control or nontreated hearts. Furthermore, the gene transfected hearts showed better functional recovery than the heat-stressed hearts. These results indicated that overexpressed HSP70 plays a protective role in myocardial injury, suggesting the possibility that gene transfection with HSP70 may become a novel method for myocardial protection through enforcing the self-preservation systems. PMID:9120008

  20. Plin5 alleviates myocardial ischaemia/reperfusion injury by reducing oxidative stress through inhibiting the lipolysis of lipid droplets

    PubMed Central

    Zheng, Pengfei; Xie, Zhonglin; Yuan, Yuan; Sui, Wen; Wang, Chao; Gao, Xing; Zhao, Yuanlin; Zhang, Feng; Gu, Yu; Hu, Peizhen; Ye, Jing; Feng, Xuyang; Zhang, Lijun

    2017-01-01

    Myocardial ischaemia-reperfusion (I/R) injury is a complex pathophysiological process. Current research has suggested that energy metabolism disorders, of which the abnormal consumption of fatty acids is closely related, compose the main pathological basis for myocardial I/R injury. Lipid droplets (LD) are critical regulators of lipid metabolism by LD-associated proteins. Among the lipid droplet proteins, the perilipin family members regulate lipolysis and lipogenesis through different mechanisms. Plin5, an important perilipin protein, promotes LD generation and lowers fatty acid oxidation, thus protecting the myocardium from lipotoxicity. This study investigated the protective effects of Plin5 in I/R myocardium. Our results indicated that Plin5 deficiency exacerbated the myocardial infarct area, aggravated left ventricular systolic dysfunction, reduced lipid storage, and elevated free fatty acids. Plin5-deficient myocardium exhibited severely damaged mitochondria, elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity. Furthermore, the decreased phosphorylation of PI3K/Akt in Plin5-null cardiomyocytes might contribute to I/R injury aggravation. In conclusion, Plin5, a new regulator of myocardial lipid metabolism, decreases free fatty acid peroxidation by inhibiting the lipolysis of intracellular lipid droplets, thus providing cardioprotection against I/R injury and shedding new light on therapeutic solutions for I/R diseases. PMID:28218306

  1. Aging might augment reactive oxygen species (ROS) formation and affect reactive nitrogen species (RNS) level after myocardial ischemia/reperfusion in both humans and rats.

    PubMed

    Fan, Qian; Chen, Mulei; Fang, Xiangyang; Lau, Wayne Bond; Xue, Lei; Zhao, Lina; Zhang, Hui; Liang, Yan-Hong; Bai, Xi; Niu, Hong-Yu; Ye, Jing; Chen, Qing; Yang, Xinchun; Liu, Miaobing

    2013-08-01

    Previous studies indicate aging results in significantly decreased cardiac function and increased myocardial apoptosis after myocardial ischemia/reperfusion (MI/R) in humans or rats. The underlying mechanisms of aging-exacerbated effects remain unknown. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are known to play vital roles in aging-related MI/R injury. Heretofore, the effects of aging upon ROS and RNS formation were not investigated in humans, which is the focus of the current study. Due to experimental limitations with clinical trials, an additional animal experiment was performed. All enrolled acute myocardial infarction (AMI) patients received percutaneous coronary intervention (PCI) therapy. AMI patients were assigned into two groups: adult (age <65, n = 34) and elderly (age ≥65, n = 45) AMI patients. Blood samples were obtained from all study participants at 24 h and 3 days post-PCI. Plasma/white blood cell (WBC) ROS and RNS markers (malondialdehyde (MDA), myeloperoxidase (MPO), reduced glutathione (GSH), inducible nitric oxide synthase (iNOS) activity, NOx, and nitrotyrosine) were determined. The same markers were determined in rat cardiac tissue after 24 h MI/R. Compared to the adult group, elderly patients manifested increased plasma MDA and MPO and decreased plasma GSH concentrations. No significant differences in plasma NOx or nitrotyrosine concentration existed between adult and elderly patients. Furthermore, WBC iNOS activity in elderly patients was significantly decreased compared to the adult group. The measurement of ROS markers in the rat experiments was consistent and supported human study data. Surprisingly, RNS markers (NOx and nitrotyrosine) in blood and heart tissue increased from young to middle-aged rats but decreased from middle age to old age. Aging augments ROS, which might exacerbate MI/R injury. Additionally, our data support aging-induced changes of RNS levels in humans and rats in vivo.

  2. Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation

    PubMed Central

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2016-01-01

    There is strong evidence to suggest that angiotensin-converting enzyme inhibitors (ACEIs) protect against local myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore whether ACEIs exert cardioprotective effects in a swine model of cardiac arrest (CA) and resuscitation. Male pigs were randomly assigned to three groups: sham-operated group, saline treatment group and enalapril treatment group. Thirty minutes after drug infusion, the animals in the saline and enalapril groups were subjected to ventricular fibrillation (8 min) followed by cardiopulmonary resuscitation (up to 30 min). Cardiac function was monitored, and myocardial tissue and blood were collected for analysis. Enalapril pre-treatment did not improve cardiac function or the 6-h survival rate after CA and resuscitation; however, this intervention ameliorated myocardial ultrastructural damage, reduced the level of plasma cardiac troponin I and decreased myocardial apoptosis. Plasma angiotensin (Ang) II and Ang-(1–7) levels were enhanced in the model of CA and resuscitation. Enalapril reduced the plasma Ang II level at 4 and 6 h after the return of spontaneous circulation whereas enalapril did not affect the plasma Ang-(1–7) level. Enalapril pre-treatment decreased the myocardial mRNA and protein expression of angiotensin-converting enzyme (ACE). Enalapril treatment also reduced the myocardial ACE/ACE2 ratio, both at the mRNA and the protein level. Enalapril pre-treatment did not affect the upregulation of ACE2, Ang II type 1 receptor (AT1R) and MAS after CA and resuscitation. Taken together, these findings suggest that enalapril protects against ischemic injury through the attenuation of the ACE/Ang II/AT1R axis after CA and resuscitation in pigs. These results suggest the potential therapeutic value of ACEIs in patients with CA. PMID:27633002

  3. Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

    PubMed Central

    la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

    2013-01-01

    OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

  4. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    PubMed

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  5. Classical and remote post-conditioning effects on ischemia/reperfusion-induced acute oxidant kidney injury.

    PubMed

    Kadkhodaee, Mehri; Najafi, Atefeh; Seifi, Behjat

    2014-11-01

    The present study aimed to analyze and compare the effects of classical and remote ischemic postconditioning (POC) on rat renal ischemia/reperfusion (IR)-induced acute kidney injury. After right nephrectomy, male rats were randomly assigned into four groups (n = 8). In the IR group, 45 min of left renal artery occlusion was induced followed by 24 h of reperfusion. In the classical POC group, after induction of 45 min ischemia, 4 cycles of 10 s of intermittent ischemia and reperfusion were applied to the kidney before complete restoring of renal blood. In the remote POC group, 4 cycles of 5 min ischemia and reperfusion of left femoral artery were applied after 45 min renal ischemia and right at the time of renal reperfusion. There was a reduction in renal function (increase in blood urea and creatinine) in the IR group. Application of both forms of POC prevented the IR-induced reduction in renal function and histology. There were also significant improvements in kidney oxidative stress status in both POC groups demonstrated by a reduction in malondialdehyde (MDA) formation and preservation of antioxidant levels comparing to the IR group. We concluded that both methods of POC have protective effects on renal function and histology possibly by a reduction in IR-induced oxidative stress.

  6. Fenofibrate plus Metformin Produces Cardioprotection in a Type 2 Diabetes and Acute Myocardial Infarction Model

    PubMed Central

    Oidor-Chan, Víctor Hugo; Hong, Enrique; Pérez-Severiano, Francisca; Montes, Sergio; Torres-Narváez, Juan Carlos; del Valle-Mondragón, Leonardo; Pastelín-Hernández, Gustavo; Sánchez-Mendoza, Alicia

    2016-01-01

    We investigated whether fenofibrate, metformin, and their combination generate cardioprotection in a rat model of type 2 diabetes (T2D) and acute myocardial infarction (AMI). Streptozotocin-induced diabetic- (DB-) rats received 14 days of either vehicle, fenofibrate, metformin, or their combination and immediately after underwent myocardial ischemia/reperfusion (I/R). Fenofibrate plus metformin generated cardioprotection in a DBI/R model, reported as decreased coronary vascular resistance, compared to DBI/R-Vehicle, smaller infarct size, and increased cardiac work. The subchronic treatment with fenofibrate plus metformin increased, compared with DBI/R-Vehicle, total antioxidant capacity, manganese-dependent superoxide dismutase activity (MnSOD), guanosine triphosphate cyclohydrolase I (GTPCH-I) expression, tetrahydrobiopterin : dihydrobiopterin (BH4 : BH2) ratio, endothelial nitric oxide synthase (eNOS) activity, nitric oxide (NO) bioavailability, and decreased inducible NOS (iNOS) activity. These findings suggest that PPARα activation by fenofibrate + metformin, at low doses, generates cardioprotection in a rat model of T2D and AMI and may represent a novel treatment strategy to limit I/R injury in patients with T2D. PMID:27069466

  7. [Double post-acute myocardial infarction complication: rupture of the interventricular septum and acute mitral insufficiency].

    PubMed

    Curcio Ruigómez, A; Martín Jiménez, J; Wilhelmi Ayza, M; Soria Delgado, J L

    1997-02-01

    We present a case of double post acute myocardial infarction complication: ventricular septal defect and acute and severe mitral insufficiency. As a consequence of the delay in the diagnosis, the patient developed pulmonary hypertension with values at the systemic level. The patient underwent surgery in order to close the ventricular septal defect and aneurysmectomy, resulting in posterior regression of mitral insufficiency and pulmonary circuit values became normal. The ethology, diagnosis, evolution and treatment of this exceptional association of acute post myocardial infarction complications are discussed.

  8. Suboptimal medical care of patients with ST-Elevation Myocardial Infarction and Renal Insufficiency: results from the Korea acute Myocardial Infarction Registry

    PubMed Central

    2012-01-01

    Background The clinical outcomes of ST-segment elevation myocardial infarction (STEMI) are poor in patients with renal insufficiency. This study investigated changes in the likelihood that patients received optimal medical care throughout the entire process of myocardial infarction management, on the basis of their glomerular filtration rate (GFR). Methods This study analyzed 7,679 patients (age, 63 ± 13 years; men 73.6%) who had STEMI and were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) from November 2005 to August 2008. The study subjects were divided into 5 groups corresponding to strata used to define chronic kidney disease stages. Results Patients with lower GFR were less likely to present with typical chest pain. The average symptom-to-door time, door-to-balloon time, and symptom-to-balloon time were longer with lower GFR than higher GFR. Primary reperfusion therapy was performed less frequently and the results of reperfusion therapy were poorer in patients with renal insufficiency; these patients were less likely to receive adjunctive medical treatment, such as treatment with aspirin, clopidogrel, β-blocker, angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB), or statin, during hospitalization and at discharge. Patients who received less intense medical therapy had worse clinical outcomes than those who received more intense medical therapy. Conclusions Patients with STEMI and renal insufficiency had less chance of receiving optimal medical care throughout the entire process of MI management, which may contribute to worse outcomes in these patients. PMID:22966970

  9. [UCP2 and UCP3 gene expression, heart function and oxygen cost of myocardial work changes during aging and ischemia-reperfusion].

    PubMed

    Hoshovs'ka, Iu V; Lisovyĭ, O O; Shymans'ka, T V; Sahach, V F

    2009-01-01

    To examine the effects of ischemia/reperfusion on UCPs genes expression, heart function and oxygen cost of myocardial work, hearts of adult (6 mo) and old (24 mo) rats were perfused by Langendorf preparation and subjected to 20 min ischemia followed by 40 min reperfusion. Mitochondrial permeability transition due to ischemic stimuli was evaluated by release of mitochondrial factor (lambda 250 nm) which was previously shown as a marker of MPTP opening. Expression of UCPs was detected by reverse transcriptional polymerase chain reaction. Mitochondrial membrane potential (deltaphi(m)) and oxygen consumption in isolated heart mitochondria of adult and old rats were measured. It was shown that impaired function of aging rat hearts was accompanied with an increased oxygen cost of myocardial work and lower mitochondrial membrane potential compared with adult rats. Reperfusion disturbances of cardiodynamic, contractile activity of myocardium and noneffective oxygen utilization in early period of reperfusion were less intensive in aged hearts than in adult ones. Therefore, the levels of mRNA of UCP2 in aging hearts were higher and mRNA levels of UCP3 were tended to increase. At the same time ischemia/reperfusion increased the expression of UCP2 and UCP3 in adult myocardium: mRNA levels of UCPs were significantly higher that those in control, whereas there was no such effect in aging hearts. It is concluded that uncoupling proteins are implicated in the age-depended heart dysfunction and development of the pathological mechanisms during ischemia-reperfusion.

  10. Depressive Symptoms Are Associated with Mental Stress-Induced Myocardial Ischemia after Acute Myocardial Infarction

    PubMed Central

    Wei, Jingkai; Pimple, Pratik; Shah, Amit J.; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon A.; Ibeanu, Ijeoma; Murrah, Nancy; Shallenberger, Lucy; Raggi, Paolo; Vaccarino, Viola

    2014-01-01

    Objectives Depression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI. Methods We studied 98 patients (49 women and 49 men) age 38–60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task), and after exercise or pharmacological stress. A summed difference score (SDS), obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores. Results There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30), p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56), p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress. Conclusion Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological) stress. PMID:25061993

  11. A myocardial ischemia- and reperfusion-induced injury is mediated by reactive oxygen species released from blood platelets.

    PubMed

    Seligmann, Christian; Prechtl, Gerald; Kusus-Seligmann, Magda; Daniel, Werner G

    2013-01-01

    In recent experimental studies, blood platelets have been found to exhibit some cardiodepressive effects in ischemic and reperfused guinea pig hearts independent of thrombus formation. These effects seemed to be mediated by reactive oxygen species (ROS). However, the source of these ROS - platelets or heart - remained still unknown. Isolated, buffer-perfused and pressure-volume work performing guinea pig hearts were exposed to a low-flow ischemia (1 ml/min) of 30 min duration and reperfused at a constant flow of 5 ml/min. Human thrombocytes were administered as 1 min bolus (20 000 thrombocytes/µl perfusion buffer) in the 15th min of ischemia or in the 1st or 5th min of reperfusion in the presence of thrombin (0.3 U/ml perfusion buffer). Recovery of external heart work (REHW) was expressed as ratio between postischemic and preischemic EHW in percent. Intracoronary platelet retention (RET) was quantified as percent of platelets applied. In a second set of experiments, thrombocytes were incubated with 10 µM of the irreversible NADPH oxidase blocker diphenyliodonium chloride and washed twice, thereafter, and administered according to the same protocol as described above. Hearts exposed to ischemia and reperfusion in the presence of thrombin but without application of platelets served as controls. Controls without application of platelets did not reveal a severe compromisation of myocardial function (REHW 85.5 ± 1%). However, addition of platelets during ischemia or in the 1st or 5th min of reperfusion led to a significant reduction of REHW as compared with controls (REHW 62.4 ± 6, 53.9 ± 3, 40.5 ± 3, respectively). Application of platelets pretreated with diphenyliodonium chloride did not reveal any cardiodepressive effects being significantly different from controls without platelet application. Moreover, treatment of platelets with diphenyliodonium chloride did not significantly decrease intracoronary platelet retention. In conclusion, these results demonstrate

  12. Management of acute perioperative myocardial infarction: a case report of concomitant acute myocardial infarction and tumor bleeding in the transverse colon

    PubMed Central

    Li, Yu-Feng; Gao, Wen-Qian; Li, Yuan-Xin; Feng, Quan-Zhou; Zhu, Ping

    2016-01-01

    Acute myocardial infarction complicated by bleeding colon tumor is problematic with regard to management, and appropriate balance of antiplatelet or anticoagulation therapy and hemostasis or surgery is crucial for effective treatment. Here, we present a case of concomitant acute myocardial infarction and bleeding tumor in the transverse colon, and share our experience of successfully balancing anticoagulation therapy and hemostasis. PMID:26937182

  13. The production of hydrogen sulfide limits myocardial ischemia and reperfusion injury and contributes to the cardioprotective effects of preconditioning with endotoxin, but not ischemia in the rat.

    PubMed

    Sivarajah, A; McDonald, M C; Thiemermann, C

    2006-08-01

    We investigated whether (endogenous) hydrogen sulfide (H2S) protects the heart against myocardial ischemia and reperfusion injury. Furthermore, we investigated whether endogenous H2S is involved in the protection afforded by (1) ischemic preconditioning and (2) the second window of protection caused by endotoxin. The involvement of one of the potential (end) effectors of the cardioprotection afforded by H2S was investigated using the mitochondrial KATP channel blocker, 5-hydroxydecanoate (5-HD; 5 mg/kg). Animals were subjected to 25 min regional myocardial ischemia followed by reperfusion (2 h) and were pretreated with the H2S donor, sodium hydrosulfide (3 mg/kg i.v.). Animals were also subjected to shorter periods of myocardial ischemia (15 min) and reperfusion (2 h) and pretreated with an irreversible inhibitor of cystathionine-gamma-lyase, dl-propargylglycine (PAG; 50 mg/kg i.v.). Animals were also pretreated with PAG (50 mg/kg) and subjected to either (1) ischemic preconditioning or (2) endotoxin (1 mg/kg i.p.) 16 h before myocardial ischemia. Myocardial infarct size was determined by p-nitroblue tetrazolium staining. Administration of sodium hydrosulfide significantly reduced myocardial infarct size, and this effect was abolished by 5-HD. Administration of PAG (50 mg/kg) or 5-HD significantly increased infarct size caused by 15 min of myocardial ischemia. The delayed cardioprotection afforded by endotoxin was abolished by 5-HD or PAG. In contrast, PAG (50 mg/kg) did not affect the cardioprotective effects of ischemic preconditioning. These findings suggest that (1) endogenous H2S is produced by myocardial ischemia in sufficient amounts to limit myocardial injury and (2) the synthesis or formation of H2S by cystathionine-gamma-lyase may contribute to the second window of protection caused by endotoxin.

  14. Glycyrrhiza glabra protects from myocardial ischemia-reperfusion injury by improving hemodynamic, biochemical, histopathological and ventricular function.

    PubMed

    Ojha, Shreesh; Golechha, Mahaveer; Kumari, Santosh; Bhatia, Jagriti; Arya, Dharamvir S

    2013-01-01

    Present study evaluated the cardioprotective effect of Glycyrrhiza glabra against ischemia-reperfusion injury (I-R) induced by ligation of left anterior descending coronary artery (LADCA) in rats. Ligation of LADCA for 45 min followed by 60 min of reperfusion has induced significant (p<0.05) heart dysfunction evidenced by significant (p<0.05) decrease in mean arterial pressure (MAP), heart rate (HR), contractility; (+)LVdP/dtmax and relaxation; (-)LVdP/dtmax along with increased left ventricular end diastolic pressure (LVEDP). Ligation induced I-R injury also significantly (p<0.05) decreased myocyte injury enzymes, creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH) as well as antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Furthermore, I-R injury also induced lipid peroxidation evidenced by significant (p<0.05) increase in malondialdehyde (MDA) formation and histological perturbations concomitant to depletion of glutathione (GSH) from heart. However, pretreatment with G. glabra significantly (p<0.05) prevented the depletion of the antioxidant enzymes; SOD, CAT, GSH-Px and myocyte injury marker enzymes; CK-MB isoenzyme and LDH. Pretreatment with G. glabra also prevented GSH depletion and inhibited lipid peroxidation in heart. In addition to improving biochemical indices of myocardial function, G. glabra also significantly (p<0.05) reinstated MAP, HR, (±)LVdP/dtmax and attenuated abrupt rise in LVEDP. Histopathological preservation evidenced by reduced infiltration of cells and myonecrosis depicted the myocardial salvaging effect of G. glabra. Taken together, results of the present study clearly suggest the cardioprotective potential of G. glabra against myocardial infarction by amelioration of oxidative stress and favorable modulation of cardiac function.

  15. Seabuckthorn Pulp Oil Protects against Myocardial Ischemia-Reperfusion Injury in Rats through Activation of Akt/eNOS.

    PubMed

    Suchal, Kapil; Bhatia, Jagriti; Malik, Salma; Malhotra, Rajiv Kumar; Gamad, Nanda; Goyal, Sameer; Nag, Tapas C; Arya, Dharamvir S; Ojha, Shreesh

    2016-01-01

    Seabuckthorn (SBT) pulp oil obtained from the fruits of seabuckthorn [Hippophae rhamnoides L. (Elaeagnaceae)] has been used traditionally for its medicinal and nutritional properties. However, its role in ischemia-reperfusion (IR) injury of myocardium in rats has not been elucidated so far. The present study reports the cardioprotective effect of SBT pulp oil in IR-induced model of myocardial infarction in rats and underlying mechanism mediating activation of Akt/eNOS signaling pathway. Male albino Wistar rats were orally administered SBT pulp oil (5, 10, and 20 ml/kg/day) or saline for 30 days. On the day 31, ischemia was induced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. SBT pulp oil pretreatment at the dose of 20 ml/kg observed to stabilize cardiac function and myocardial antioxidants such as glutathione, superoxide dismutase, catalase, and inhibited lipid peroxidation evidenced by reduced malondialdehyde levels as compared to IR-control group. SBT pulp oil also improved hemodynamic and contractile function and decreased tumor necrosis factor and activities of myocyte injury marker enzymes; lactate dehydrogenase and creatine kinase-MB. Additionally, a remarkable rise in expression of pAkt-eNOS, Bcl-2 and decline in expression of IKKβ/NF-κB and Bax was observed in the myocardium. The histopathological and ultrastructural salvage of cardiomyocytes further supports the cardioprotective effect of SBT pulp oil. Based on findings, it can be concluded that SBT pulp oil protects against myocardial IR injury mediating favorable modulation of Akt-eNOS and IKKβ/NF-κB expression.

  16. Seabuckthorn Pulp Oil Protects against Myocardial Ischemia–Reperfusion Injury in Rats through Activation of Akt/eNOS

    PubMed Central

    Suchal, Kapil; Bhatia, Jagriti; Malik, Salma; Malhotra, Rajiv Kumar; Gamad, Nanda; Goyal, Sameer; Nag, Tapas C.; Arya, Dharamvir S.; Ojha, Shreesh

    2016-01-01

    Seabuckthorn (SBT) pulp oil obtained from the fruits of seabuckthorn [Hippophae rhamnoides L. (Elaeagnaceae)] has been used traditionally for its medicinal and nutritional properties. However, its role in ischemia–reperfusion (IR) injury of myocardium in rats has not been elucidated so far. The present study reports the cardioprotective effect of SBT pulp oil in IR-induced model of myocardial infarction in rats and underlying mechanism mediating activation of Akt/eNOS signaling pathway. Male albino Wistar rats were orally administered SBT pulp oil (5, 10, and 20 ml/kg/day) or saline for 30 days. On the day 31, ischemia was induced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. SBT pulp oil pretreatment at the dose of 20 ml/kg observed to stabilize cardiac function and myocardial antioxidants such as glutathione, superoxide dismutase, catalase, and inhibited lipid peroxidation evidenced by reduced malondialdehyde levels as compared to IR-control group. SBT pulp oil also improved hemodynamic and contractile function and decreased tumor necrosis factor and activities of myocyte injury marker enzymes; lactate dehydrogenase and creatine kinase-MB. Additionally, a remarkable rise in expression of pAkt–eNOS, Bcl-2 and decline in expression of IKKβ/NF-κB and Bax was observed in the myocardium. The histopathological and ultrastructural salvage of cardiomyocytes further supports the cardioprotective effect of SBT pulp oil. Based on findings, it can be concluded that SBT pulp oil protects against myocardial IR injury mediating favorable modulation of Akt-eNOS and IKKβ/NF-κB expression. PMID:27445803

  17. Cardiac Per2 Functions as Novel Link between Fatty Acid Metabolism and Myocardial Inflammation during Ischemia and Reperfusion Injury of the Heart

    PubMed Central

    Bonney, Stephanie; Kominsky, Doug; Brodsky, Kelley; Eltzschig, Holger; Walker, Lori; Eckle, Tobias

    2013-01-01

    Disruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In contrast to Clock−/−, Per2−/− mice have larger infarct sizes with deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we measured lactate during reperfusion in Per1−/−, Per2−/− or wildtype mice. As lactate measurements in whole blood indicated an exclusive role of Per2 in controlling lactate production during myocardial ischemia, we next performed gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2−/− mice. Surprisingly, high-throughput gene array analysis revealed dominantly lipid metabolism as the differentially regulated pathway in wildtype mice when compared to Per2−/−. In all ischemia-reperfusion protocols used, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI) confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2−/− mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated ‘Per2-genes’. Subsequent studies on inflammatory markers showed increasing IL-6 or TNFα levels during reperfusion in Per2−/− mice. In summary, these studies reveal an important role of cardiac Per2 for fatty acid metabolism and inflammation during myocardial ischemia and reperfusion, respectively. PMID:23977055

  18. MicroRNAs regulate mitochondrial apoptotic pathway in myocardial ischemia-reperfusion-injury.

    PubMed

    Makhdoumi, Pouran; Roohbakhsh, Ali; Karimi, Gholamreza

    2016-12-01

    MicroRNAs (miRNAs) are small non-coding RNAs that act as post-transcriptional gene regulators. They are involved in the pathogenesis of different disorders including heart diseases. MiRNAs contribute to ischemia/reperfusion injury (I/RI) by altering numerous key signaling elements. Together with alterations in the various potential signaling pathways, modification in miRNA expression has been suggested as a part of the response network following ischemia/reperfusion (I/R). In addition, cardiac mitochondrial homeostasis is closely associated with cardiac function and impairment of mitochondrial activity occurred after ischemia/reperfusion injury. MiRNAs play a key role in the regulation of mitochondrial apoptotic pathway and signaling proteins. In this review, we summarize the knowledge currently available regarding the molecular mechanisms of miRNA-regulated mitochondrial functions during ischemia/reperfusion injury. This regulation occurs in different stages of mitochondrial apoptosis pathway.

  19. [Sexuality in acute myocardial infarction patients].

    PubMed

    Casado Dones, Ma J; de Andrés Gimeno, B; Moreno González, C; Fernández Balcones, C; Cruz Martín, R Ma; Colmenar García, C

    2002-01-01

    We as nurses in the Coronary Unit we do not see the sexuality of the patients sufficiently addressed neither by us nor by the patients themselves. In this article we are trying to analize the reasons and to emphasize the need to include this subject in our Nursing Problem List. In it we explaine the fears and the wrong ideas that we have identified in our patients. The sexual function is not affected by a myocardial infarction but psychological factors, age, drugs and other associated diseases might be a reason. A quiet enviroment, a fit training plan and looking for personalise proper alternatives may help the patient to start a satisfactory sexual life again.

  20. Venlafaxine induced acute myocardial infarction with normal coronary arteries.

    PubMed

    Godkar, Darshan; Stensby, Jessica; Sinnapunayagam, Selvaratnam; Niranjan, Selva

    2009-01-01

    We describe the case of a 51-year-old female with no risk factors for coronary artery disease who had an episode of a non-ST-elevation myocardial infarction in association with an overdose of Venlafaxine. Cardiac catheterization revealed normal coronary arteries. Because no other obvious exacerbating factors for ischemia were observed, we assume that this drug may have contributed to the development of an acute ischemic event because of its pharmacologic properties.

  1. [Acute myocardial infarction during tocolytic treatment with ritodrine].

    PubMed

    Fornet, I; Calvo, M; Gimeno, M; Canser, E; Alonso, E; Gilsanz, F

    2006-05-01

    Ritodrine, a beta2-adrenergic agonist with a selective effect on the uterine muscle, is prescribed to prevent premature labor and to treat a hypertonic uterus. At therapeutic doses ritodrine has chronotropic and peripheral vasodilator effects. At high doses it has been related to sporadic cases of subendocardial necrosis, pulmonary edema, and death in pregnancy. We report the case of a pregnant woman who had a non-Q wave acute myocardial infarction after administration of ritodrine.

  2. An unusual presentation of mad honey poisoning: acute myocardial infarction.

    PubMed

    Akinci, Sinan; Arslan, Uğur; Karakurt, Kamber; Cengel, Atiye

    2008-09-26

    An unusual type of food poisoning is commonly seen in the Black Sea coast of Turkey due to grayanotoxin containing toxic honey so called "mad honey" ingestion. In cases of toxication bradycardia and rhythm disturbances are commonly observed. Herein, we present a case of a patient who was admitted to the hospital because of acute myocardial infarction with normal coronary arteries after "mad honey" ingestion.

  3. Mechanisms Underlying Acute Protection from Cardiac Ischemia-Reperfusion Injury

    PubMed Central

    Murphy, Elizabeth; Steenbergen, Charles

    2009-01-01

    Mitochondria play an important role in cell death and cardioprotection. During ischemia, when ATP is progressively deleted, ion pumps cannot function resulting in a rise in calcium (Ca2+), which further accelerates ATP depletion. The rise in Ca2+ during ischemia and reperfusion leads to mitochondrial Ca2+ accumulation, particularly during reperfusion when oxygen is reintroduced. Reintroduction of oxygen allows generation of ATP; however damage to electron transport chain results in increased mitochondrial generation of reactive oxygen species (ROS). Mitochondrial Ca2+ overload, and increased ROS can result in opening of the mitochondrial permeability transition pore, which further compromises cellular energetics. The resultant low ATP and altered ion homeostasis result in rupture of the plasma membrane and cell death. Mitochondria have long been proposed as central players in cell death, since the mitochondria are central to synthesis of both ATP and ROS and since mitochondrial and cytosolic Ca2+ overload are key components of cell death. Many cardioprotective mechanisms converge on the mitochondria to reduce cell death. Reducing Ca2+ overload and reducing ROS have both been reported to reduce ischemic injury. Preconditioning activates a number of signaling pathways that reduce Ca2+ overload and reduce activation of the mitochondrial permeability transition pore. The mitochondrial targets of cardioprotective signals will be discussed in detail. PMID:18391174

  4. A Type A Aortic Dissection Mimicking an Acute Myocardial Infarction

    PubMed Central

    D’Aloia, Antonio; Vizzardi, Enrico; Bugatti, Silvia; Magatelli, Marco; Bonadei, Ivano; Rovetta, Riccardo; Quinzani, Filippo; Curnis, Antonio; Cas, Livio Dei

    2012-01-01

    We describe a case of a 54 years old man in whom an initial diagnosis of acute coronary syndrome (ACS) revealed to be finally an acute aortic dissection. This case report stresses the importance to maintain a high grade of suspicion of aortic dissection as a possible alternative in presence of eletrocardiographic myocardial ischemic signs. In many medical centers where thrombolitic therapy, antiplatelets receptor blockers, heparin or percutaneous coronary angioplasty is the first line therapy for ACS the outcome may be catastrophic in situation such as aortic dissection.

  5. Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction

    PubMed Central

    Teren, A.; Kirsten, H.; Beutner, F.; Scholz, M.; Holdt, L. M.; Teupser, D.; Gutberlet, M.; Thiery, J.; Schuler, G.; Eitel, I.

    2017-01-01

    Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15–25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 × 10−5), and regulation of inflammatory response (p = 1.86 × 10−3). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction. PMID:28155873

  6. Ablation of C/EBP homologous protein increases the acute phase mortality and doesn't attenuate cardiac remodeling in mice with myocardial infarction.

    PubMed

    Luo, Guangjin; Li, Qingman; Zhang, Xiajun; Shen, Liang; Xie, Jiahe; Zhang, Jingwen; Kitakaze, Masafumi; Huang, Xiaobo; Liao, Yulin

    2015-08-14

    Endoplasmic reticulum stress is a proapoptotic and profibrotic stimulus. Ablation of C/EBP homologous protein (CHOP) is reported to reverse cardiac dysfunction by attenuating cardiac endoplasmic reticulum stress in mice with pressure overload or ischemia/reperfusion, but it is unclear whether loss of CHOP also inhibits cardiac remodeling induced by permanent-infarction. In mice with permanent ligation of left coronary artery, we found that ablation of CHOP increased the acute phase mortality. For the mice survived to 4 weeks, left ventricular anterior (LV) wall thickness was larger in CHOP knockout mice than in the wildtype littermates, while no difference was noted on posterior wall thickness, LV dimensions, LV fractional shortening and ejection fraction. Similarly, invasive assessment of LV hemodynamics, morphological analysis of heart and lung weight indexes, myocardial fibrosis and TUNEL-assessed apoptosis showed no significant differences between CHOP knockout mice and their wildtype ones, while in mice with ischemia for 45 min and reperfusion for 1 week, myocardial fibrosis and apoptosis in the infarct area were significantly attenuated in CHOP knockout mice. These findings indicate that ablation of CHOP doesn't ameliorate cardiac remodeling induced by permanent-myocardial infarction, which implicates that early reperfusion is a prerequisite for ischemic myocardium to benefit from CHOP inhibition.

  7. Resveratrol attenuates myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B.

    PubMed

    Yang, Lei; Zhang, Yan; Zhu, Mengmeng; Zhang, Qiong; Wang, Xiaoling; Wang, Yanjiao; Zhang, Jincai; Li, Jing; Yang, Liang; Liu, Jie; Liu, Fei; Yang, Yinan; Kang, Licheng; Shen, Yanna; Qi, Zhi

    2016-12-01

    The objective was to examine the protective effect of resveratrol (RSV) on myocardial ischemia/reperfusion (IR) injury and whether the mechanism was related to vascular endothelial growth factor B (VEGF-B) signaling pathway. Rat hearts were isolated for Langendorff perfusion test and H9c2 cells were used for in vitro assessments. RSV treatment significantly improved left ventricular function, inhibited CK-MB release, and reduced infarct size in comparison with IR group ex vivo. RSV treatment markedly decreased cell death and apoptosis of H9c2 cells during IR. We found that RSV was responsible for the up-regulation of VEGF-B mRNA and protein level, which caused the activation of Akt and the inhibition of GSK3β. Additionally, RSV prevented the generation of reactive oxygen species (ROS) by up-regulating the expression of MnSOD either in vitro or ex vivo. We also found that the inhibition of VEGF-B abolished the cardioprotective effect of RSV, increased apoptosis, and led to the down-regulation of phosphorylated Akt, GSK3β, and MnSOD in H9c2 cells. These results demonstrated that RSV was able to attenuate myocardial IR injury via promotion of VEGF-B/antioxidant signaling pathway. Therefore, the up-regulation of VEGF-B can be a promising modality for clinical myocardial IR injury therapy.

  8. Effect of Salvia miltiorrhiza and ligustrazine injection on myocardial ischemia/reperfusion and hypoxia/reoxygenation injury

    PubMed Central

    Huang, Wendong; Yang, Yongfei; Zeng, Zhi; Su, Meiling; Gao, Qi; Zhu, Banghao

    2016-01-01

    Salvia miltiorrhiza and ligustrazine are traditional Chinese medicines that have been used in combination for treatment of cardiovascular disease, including coronary heart disease, cardiac angina and atherosclerosis in Asia, in particular, China. The present study aimed to determine the effect of S. miltiorrhiza and ligustrazine injection (SLI) on myocardial ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) injuries via the Akt serine/threonine kinase (Akt)-endothelial nitric oxide synthase (eNOS) signaling pathway. Male Sprague-Dawley rats were randomly assigned into six groups: i) Sham group; ii) I/R group; iii) Low-SLI group (6.8 mg/kg/day, i.p.); iv) Medium-SLI group (20.4 mg/kg/day, i.p.); v) High-SLI group (61.2 mg/kg/day, i.p.); vi) verapamil group (6 mg/kg/day, i.p.). Prior to surgery, the aforementioned groups were pretreated with a homologous drug once per day for 3 days. The effect of SLI following 35 min coronary artery occlusion and 2 h reperfusion was evaluated by determining infarct size, hemodynamics, biochemical values and histological observations. Additionally, cell viability, caspase-3 expression, B cell leukemia/lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio, phosphorylated (p-)Akt and p-eNOS were also investigated following 2 h simulated ischemia and 2 h simulated reperfusion in H9C2 cardiomyocyte cells. Pretreatment with SLI significantly improved cardiac function in a dose-dependent manner and reduced myocardial infarct size, creatine kinase, lactate dehydrogenase and malondialdehyde levels in blood serum. Additionally, myocardial histopathology changes in the rat model were also alleviated in SLI treatment groups. The present in vitro study revealed that treatment with SLI reduced the apoptotic rate of H9C2 cells by inhibiting the activation of caspase-3 and increasing the Bcl-2/Bax ratio. The effect of SLI was associated with increased phosphorylation of the survival kinase Akt at Ser473 and its downstream target e

  9. Phosphodiesterase-5 Inhibitor, Tadalafil, Protects against Myocardial Ischemia/Reperfusion through Protein-Kinase G Dependent Generation of Hydrogen Sulfide

    PubMed Central

    Salloum, Fadi N.; Chau, Vinh Q.; Hoke, Nicholas N.; Abbate, Antonio; Varma, Amit; Ockaili, Ramzi A.; Toldo, Stefano; Kukreja, Rakesh C.

    2014-01-01

    Background Tadalafil is a novel long acting inhibitor of phosphodiesterase-5. Since cGMP-dependent protein kinase (PKG) signaling plays a key role in cardioprotection, we hypothesized that PKG activation with tadalafil would limit myocardial ischemia/reperfusion (I/R) injury and dysfunction. Additionally, we contemplated that cardioprotection with tadalafil is mediated by hydrogen sulfide (H2S) signaling in a PKG-dependent fashion. Methods and Results After baseline transthoracic echocardiography (TTE), adult ICR mice were injected i.p. with vehicle (10% DMSO) or tadalafil (1 mg/kg) with or without KT5823 (KT, PKG blocker, 1 mg/kg) or dl-propargylglycine [PAG, Cystathionine-γ-lyase (CSE, H2S-producing enzyme) blocker; 50 mg/kg] 1 h prior to coronary artery ligation for 30 min and reperfusion for 24 h, whereas C57BL-wild type and CSE-knockout mice were treated with either vehicle or tadalafil. After reperfusion, TTE was performed and hearts were collected for infarct size (IS) measurement using TTC staining. Survival was increased with tadalafil (95%) compared with control (65%, P<0.05). Infarct size was reduced with tadalafil (13.2±1.7%) compared to vehicle (40.6±2.5%; P<0.05). KT and PAG abolished tadalafil-induced protection (IS: 39.2±1% and 51.2±2.4%, respectively) similar to genetic deletion of CSE (47.2±5.1%). Moreover, tadalafil preserved fractional shortening (FS: 31±1.5%) compared to control (FS: 22±4.8%, P<0.05). Baseline FS was 44±1.7%. KT and PAG abrogated the preservation of LV function with tadalafil by a decline in FS to 17±1% and 23±3%, respectively. Compared to vehicle, myocardial H2S production was significantly increased with tadalafil and was abolished with KT. Conclusion PKG activation with tadalafil limits myocardial infarction and preserves LV function through H2S signaling. PMID:19752383

  10. Changes of endothelin-1 and big endothelin-1 levels and action potential duration during myocardial ischemia-reperfusion in dogs with and without ventricular fibrillation.

    PubMed

    Vágó, Hajnalka; Soós, Pál; Zima, Endre; Gellér, László; Keltai, Katalin; Róka, Attila; Kékesi, Violetta; Juhász-Nagy, Alexander; Merkely, Béla

    2004-11-01

    Myocardial ischemia-reperfusion is associated with increased production of endothelin-1 (ET-1). Moreover, exogenous ET-1 has arrhythmogenic properties. Our aim was to investigate the correlation between endogenous ET-1, big ET-1 levels and epicardial monophasic action potential duration during myocardial ischemia-reperfusion in anesthetized dogs. Thirty-minute myocardial ischemia was followed by a 90-minute reperfusion period in 18 mongrel dogs. The total incidence of ventricular fibrillation (VF) during ischemia and reperfusion was 11.1% and 33.3%, respectively. During ischemia, the monophasic action potential duration at 90% repolarization (MAPD90) decreased significantly (control versus ischemia, 30 minutes, 224.7 +/- 7.1 ms versus 173.8 +/- 7.6 ms; P < 0.05), while during reperfusion a significant prolongation of MAPD90 was observed (ischemia, 30 minutes versus reperfusion, 30 minutes, 173.8 +/- 7.6 ms versus 249.7 +/- 9.9 ms, P < 0.05). During reperfusion ET-1 and big ET-1 levels increased significantly in the coronary sinus and femoral artery (control versus reperfusion, 90 minutes: coronary sinus ET-1, 15.1 +/- 1.4 fmol/mL versus 22.3 +/- 1.1 fmol/mL; big ET-1, 14.7 +/- 1.9 fmol/mL versus 27.4 +/- 2.3 fmol/mL; P < 0.05). The ET-1 concentration increased to a higher level during ischemia in dogs with VF compared with dogs surviving ischemia-reperfusion (non-VF versus VF: control, 15.1 +/- 1.3 versus 15.2 +/- 1.3; ischemia, 30 minutes, 17.6 +/- 1.2 fmol/mL versus 22 +/- 1.6 fmol/mL; P < 0.05), demonstrating a trend of correlation between endothelin levels and development of VF (P = 0.07). ET-1 and big ET-1 levels increased during reperfusion and in the VF group during ischemia; however, there was no correlation between endothelin levels and MAPD90.

  11. [Whole blood viscosity measurement in acute myocardial infarction: feasibility and significance].

    PubMed

    Philippe, F; Lacombe, C; Bucherer, C; Drobinski, G; Montalescot, G; Thomas, D

    2001-10-01

    Thrombolytic agents and new antiplatelet drugs used in acute myocardial infarction (AMI) could change whole blood viscosity. The aim of this pilot trial is to compare blood viscosity at four shear rate levels among three groups of patients: AMI receiving thrombolysis with alteplase (n: 10), AMI eligible for primary angioplasty with abciximab (n: 10), healthy volunteers (n: 10). Viscosity measurement was obtained in 30 minutes with a Couette hemoviscosimeter. At baseline, blood viscosity level was higher in patients with acute coronary syndromes than in healthy volunteers (72 +/- 32 mPa.s versus 51 +/- 13 mPa.s, p<0.05). After thrombolysis, viscosity was higher at 90 minutes than at third day, paradoxically with fibrinogen elevation (72 +/- 32 mPa.s versus 58 +/- 27 mPa.s, p=0.01). In primary angioplasty with abciximab, viscosity decreased significantly (56 +/- 28 mPa.s versus 43 +/- 13 mPa.s, p=0.01). The effects of ionic contrast agent and abciximab are discussed. In healthy volunteers group, 100 mg aspirin once a day during 7 days reduces blood viscosity at high shear stress. The small size of the study population restricts correlation analysis with major clinical adverse events. A larger trial is necessary to evaluate the predictive value of whole blood viscosity in reocclusive and/or hemorrhagic events in those reperfusion strategies but also in case of thrombolytic agent and abciximab combination.

  12. Safety and efficacy of repeat thrombolytic treatment after acute myocardial infarction.

    PubMed Central

    White, H D; Cross, D B; Williams, B F; Norris, R M

    1990-01-01

    Thrombolytic treatment for acute myocardial infarction increases the risk of subsequent reocclusion of the infarct related artery. The efficacy and safety of repeat thrombolytic treatment was assessed in 31 patients treated with streptokinase (n = 13) or tissue plasminogen activator (n = 18) a median of five days (1-716) after the first infusion. The indication for readministration was prolonged chest pain with new ST segment elevation. Efficacy was assessed by infarct artery patency at angiography at a median of eight days after readministration in 22 patients and by non-invasive criteria in 23 patients (reperfusion was deemed to be likely if serum creatine kinase was not increased or reached a peak less than 12 hours after infarction). Angiography showed patency of 70% of the infarct arteries after readministration of streptokinase and of 75% after tissue plasminogen activator. The corresponding patency rates assessed noninvasively were 73% and 75%. Reinfarction was prevented in nine (29%) patients. Allergic reactions occurred in four of eight patients who received streptokinase twice (plasmacytosis and acute reversible renal failure developed in one patient). Two patients had major bleeding and two minor bleeding, all after tissue plasminogen activator, and one of them died of cerebral haemorrhage. Repeat thrombolytic treatment results in late patency rates similar to the rates after the initial administration. Allergic reactions were common in those treated twice with streptokinase. PMID:2119665

  13. Hemodynamic effects of acute digitalization several months after acute myocardial infarction.

    PubMed

    Ressl, J; Jandová, R; Jebavý, P; Kasalický, J; Widimský, J

    1975-01-01

    Left ventricular function was investigated at rest and during exercise by heart catheterization in 15 patients 3-5 months after acute myocardial infarction. The effect of 1 mg digoxin i.v. in ten patients was correlated to placebo (saline solution) in five patients. A significant decrease of the left ventricular enddiastolic pressure, increase of left ventricular systolic ejection fraction and a shift of the left ventricular function curve to left upwards was found after digoxin with no changes in the placebo group. This beneficial effect of acute digitalization in patients convalescing from uncomplicated myocardial infarction without clinical signs of manifest heart failure could have therapeutic implication.

  14. Analysis of temporal dynamics in imagery during acute limb ischemia and reperfusion

    NASA Astrophysics Data System (ADS)

    Irvine, John M.; Regan, John; Spain, Tammy A.; Caruso, Joseph D.; Rodriquez, Maricela; Luthra, Rajiv; Forsberg, Jonathon; Crane, Nicole J.; Elster, Eric

    2014-03-01

    Ischemia and reperfusion injuries present major challenges for both military and civilian medicine. Improved methods for assessing the effects and predicting outcome could guide treatment decisions. Specific issues related to ischemia and reperfusion injury can include complications arising from tourniquet use, such as microvascular leakage in the limb, loss of muscle strength and systemic failures leading to hypotension and cardiac failure. Better methods for assessing the viability of limbs/tissues during ischemia and reducing complications arising from reperfusion are critical to improving clinical outcomes for at-risk patients. The purpose of this research is to develop and assess possible prediction models of outcome for acute limb ischemia using a pre-clinical model. Our model relies only on non-invasive imaging data acquired from an animal study. Outcome is measured by pathology and functional scores. We explore color, texture, and temporal features derived from both color and thermal motion imagery acquired during ischemia and reperfusion. The imagery features form the explanatory variables in a model for predicting outcome. Comparing model performance to outcome prediction based on direct observation of blood chemistry, blood gas, urinalysis, and physiological measurements provides a reference standard. Initial results show excellent performance for the imagery-base model, compared to predictions based direct measurements. This paper will present the models and supporting analysis, followed by recommendations for future investigations.

  15. The ET(A) receptor antagonist LU 135252 has no electrophysiological or anti-arrhythmic effects during myocardial ischaemia/reperfusion in dogs.

    PubMed

    Vágó, Hajnalka; Soós, Pál; Zima, Endre; Gellér, László; Kékesi, Violetta; Andrási, Terézia; Szabó, Tamás; Juhász-Nagy, Alexander; Merkely, Béla

    2002-08-01

    The anti-arrhythmic effects of ET(A) receptor antagonists during myocardial ischaemia and reperfusion remain controversial. Moreover, the electrophysiological mechanism has not yet been identified. The aim of this study was to investigate the potential anti-arrhythmic and electrophysiological effects of the ET(A) receptor antagonist LU 135252 (LU) during myocardial ischaemia and reperfusion in a canine model. A bolus of LU (1 mg/kg; n=10) or saline (control; n=10) was injected into the left anterior descending coronary artery before ligation of this vessel for 30 min, which was followed by a 90-min reperfusion period. LU bolus administration (0.5 mg/kg) was repeated every 30 min. There were no differences in mean arterial blood pressure or coronary blood flow between the two groups. The determined left ventricular ischaemic mass was 25.5+/-1.8% and 27.8+/-2.2% of the total left ventricular mass in the control and LU groups respectively. The total incidence of ventricular fibrillation during ischaemia and reperfusion was 40% in the control and 50% in the LU group (not significantly different). The incidence of non-sustained and sustained ventricular tachycardias during ischaemia, reperfusion and over the whole period (ischaemia plus reperfusion) in the control group was 50%, 50% and 70% respectively, and that in the LU group was 80%, 70% and 100% respectively (no significant differences between groups). The number of ventricular premature beats was not decreased by LU during either ischaemia or reperfusion [median (25th-75th percentile): ischaemia, 20 (13-37) and 56 (32-130) for LU and control groups respectively; reperfusion, 15 (2-21) and 39 (7-74) respectively; ischaemia+reperfusion, 16 (4-35) and 43 (10-82) respectively; no significant differences between groups]. During ischaemia, the monophasic action potential duration at 90% repolarization (MAPD(90)) decreased significantly, while during reperfusion a significant prolongation of MAPD(90) was observed in the

  16. Modulation of Mononuclear Phagocyte Inflammatory Response by Liposome-Encapsulated Voltage Gated Sodium Channel Inhibitor Ameliorates Myocardial Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Ji, Wen-Jie; Zhang, Li; Dong, Yan; Ge, Lan; Lu, Rui-Yi; Sun, Hai-Ying; Guo, Zao-Zeng; Yang, Guo-Hong; Jiang, Tie-Min; Li, Yu-Ming

    2013-01-01

    Background Emerging evidence shows that anti-inflammatory strategies targeting inflammatory monocyte subset could reduce excessive inflammation and improve cardiovascular outcomes. Functional expression of voltage-gated sodium channels (VGSCs) have been demonstrated in monocytes and macrophages. We hypothesized that mononuclear phagocyte VGSCs are a target for monocyte/macrophage phenotypic switch, and liposome mediated inhibition of mononuclear phagocyte VGSC may attenuate myocardial ischemia/reperfusion (I/R) injury and improve post-infarction left ventricular remodeling. Methodology/Principal Findings Thin film dispersion method was used to prepare phenytoin (PHT, a non-selective VGSC inhibitor) entrapped liposomes. Pharmacokinetic study revealed that the distribution and elimination half-life of PHT entrapped liposomes were shorter than those of free PHT, indicating a rapid uptake by mononuclear phagocytes after intravenous injection. In rat peritoneal macrophages, several VGSC α subunits (NaV1.1, NaV1.3, NaV1.4, NaV1.5, NaV1.6, NaV1.7, NaVX, Scn1b, Scn3b and Scn4b) and β subunits were expressed at mRNA level, and PHT could suppress lipopolysaccharide induced M1 polarization (decreased TNF-α and CCL5 expression) and facilitate interleukin-4 induced M2 polarization (increased Arg1 and TGF-β1 expression). In vivo study using rat model of myocardial I/R injury, demonstrated that PHT entrapped liposome could partially suppress I/R injury induced CD43+ inflammatory monocyte expansion, along with decreased infarct size and left ventricular fibrosis. Transthoracic echocardiography and invasive hemodynamic analysis revealed that PHT entrapped liposome treatment could attenuate left ventricular structural and functional remodeling, as shown by increased ejection fraction, reduced end-systolic and end-diastolic volume, as well as an amelioration of left ventricular systolic (+dP/dtmax) and diastolic (-dP/dtmin) functions. Conclusions/Significance Our work for the

  17. Pathological observation of acute myocardial infarction in Chinese miniswine

    PubMed Central

    Wang, Chuang; Wang, Shao-Xin; Dong, Ping-Shuan; Wang, Li-Ping; Duan, Na-Na; Wang, Yan-Yu; Wang, Ke; Li, Zhuan-Zhen; Wei, Li-Juan; Meng, Ya-Li; Cheng, Jian-Xin

    2015-01-01

    The acute myocardial infarction (AMI) model in Chinese miniswine was built by percutaneous coronary artery occlusion. Pathological observation of AMI was performed, and the expression of tumor necrosis factor alpha (TNF-α) in the infarct sites was detected at different days after modeling in Chinese miniswine. The experimental findings may be used as the basis for blood flow reconstruction and intervention after AMI. Seven experimental Chinese miniswine were subjected to general anesthesia and Seldinger right femoral artery puncture. After coronary angiography, the gelfoam was injected via the microtube to occlude the obtuse marginal branch (OM branch). At 1 d, 3 d, 5 d, 7 d, 10 d, 14 d and 17 d after modeling, hetatoxylin-eosin (HE) staining was performed to observe the pathological changes and to detect the expression of TNF-α in the myocardial tissues. Cytoplasmic acidophilia of the necrotic myocardial tissues at 1 d after modeling was enhanced, and cytoplasmic granules were formed; at 3 d, the margins of the necrotic myocardial tissues were infiltrated by a large number of inflammatory cells; at 5 d, the nuclei of the necrotic myocardial cells were fragmented; at 7 d, extensive granulation tissues were formed at the margin of the necrotic myocardial tissues; at 10 d, part of the granulation tissues were replaced by fibrous scar tissues; at 14-17 d, all granulation tissues were replaced by fibrous scar tissues. Immunohistochemical detection indicated that no TNF-α expression in normal myocardial tissues. The TNF-α expression was first detected at 3 d in the necrotic myocardial tissues and then increased at 5 d and 7 d. After reaching the peak at 10 d, the expression began to decrease at 14 d and the decrease continued at 17 d. Coronary angiography showed the disappearance of blood flow at the distal end of OM branch occluded by gelfoam, indicating that AMI model was constructed successfully. The repair of the infarcted myocardium began at 10-17 d after

  18. Acute kidney injury and post-reperfusion syndrome in liver transplantation

    PubMed Central

    Umbro, Ilaria; Tinti, Francesca; Scalera, Irene; Evison, Felicity; Gunson, Bridget; Sharif, Adnan; Ferguson, James; Muiesan, Paolo; Mitterhofer, Anna Paola

    2016-01-01

    In the past decades liver transplantation (LT) has become the treatment of choice for patients with end stage liver disease (ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death (DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease (CKD). Acute kidney injury (AKI) post-LT has been recently recognized as an important risk factor for the occurrence of de novo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome (PRS) that can influence recipient’s morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since pre-LT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A PubMed search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on PubMed search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors

  19. Carbon monoxide increases inducible NOS expression that mediates CO-induced myocardial damage during ischemia-reperfusion.

    PubMed

    Meyer, Grégory; André, Lucas; Kleindienst, Adrien; Singh, François; Tanguy, Stéphane; Richard, Sylvain; Obert, Philippe; Boucher, François; Jover, Bernard; Cazorla, Olivier; Reboul, Cyril

    2015-04-01

    We investigated the role of inducible nitric oxide (NO) synthase (iNOS) on ischemic myocardial damage in rats exposed to daily low nontoxic levels of carbon monoxide (CO). CO is a ubiquitous environmental pollutant that impacts on mortality and morbidity from cardiovascular diseases. We have previously shown that CO exposure aggravates myocardial ischemia-reperfusion (I/R) injury partly because of increased oxidative stress. Nevertheless, cellular mechanisms underlying cardiac CO toxicity remain hypothetical. Wistar rats were exposed to simulated urban CO pollution for 4 wk. First, the effects of CO exposure on NO production and NO synthase (NOS) expression were evaluated. Myocardial I/R was performed on isolated perfused hearts in the presence or absence of S-methyl-isothiourea (1 μM), a NOS inhibitor highly specific for iNOS. Finally, Ca(2+) handling was evaluated in isolated myocytes before and after an anoxia-reoxygenation performed with or without S-methyl-isothiourea or N-acetylcystein (20 μM), a nonspecific antioxidant. Our main results revealed that 1) CO exposure altered the pattern of NOS expression, which is characterized by increased neuronal NOS and iNOS expression; 2) cardiac NO production increased in CO rats because of its overexpression of iNOS; and 3) the use of a specific inhibitor of iNOS reduced myocardial hypersensitivity to I/R (infarct size, 29 vs. 51% of risk zone) in CO rat hearts. These last results are explained by the deleterious effects of NO and reactive oxygen species overproduction by iNOS on diastolic Ca(2+) overload and myofilaments Ca(2+) sensitivity. In conclusion, this study highlights the involvement of iNOS overexpression in the pathogenesis of simulated urban CO air pollution exposure.

  20. Impact of caloric restriction on myocardial ischaemia/reperfusion injury and new therapeutic options to mimic its effects

    PubMed Central

    Rohrbach, Susanne; Aslam, Muhammad; Niemann, Bernd; Schulz, Rainer

    2014-01-01

    Caloric restriction (CR) is the most reliable intervention to extend lifespan and prevent age-related disorders in various species from yeast to rodents. Short- and long-term CR confers cardio protection against ischaemia/reperfusion injury in young and even in aged rodents. A few human trials suggest that CR has the potential to mediate improvement of cardiac or vascular function and induce retardation of cardiac senescence also in humans. The underlying mechanisms are diverse and have not yet been clearly defined. Among the known mediators for the benefits of CR are NO, the AMP-activated PK, sirtuins and adiponectin. Mitochondria, which play a central role in such complex processes within the cell as apoptosis, ATP-production or oxidative stress, are centrally involved in many aspects of CR-induced protection against ischaemic injury. Here, we discuss the relevant literature regarding the protection against myocardial ischaemia/reperfusion injury conferred by CR. Furthermore, we will discuss drug targets to mimic CR and the possible role of calorie restriction in preserving cardiovascular function in humans. PMID:24611611

  1. Evaluation of the relationship between hyperinsulinaemia and myocardial ischaemia/reperfusion injury in a rat model of depression.

    PubMed

    Solskov, Lasse; Løfgren, Bo; Pold, Rasmus; Kristiansen, Steen B; Nielsen, Torsten T; Overstreet, David H; Schmitz, Ole; Bøtker, Hans Erik; Lund, Sten; Wegener, Gregers

    2009-11-09

    Major depression is associated with medical co-morbidity, such as ischaemic heart disease and diabetes, but the underlying pathophysiological mechanisms remain unclear. The FSL (Flinders Sensitive Line) rat is a genetic animal model of depression exhibiting features similar to those of depressed individuals. The aim of the present study was to compare the myocardial responsiveness to I/R (ischaemia/reperfusion) injury and the effects of IPC (ischaemic preconditioning) in hearts from FSL rats using SD (Sprague-Dawley) rats as controls and to characterize differences in glucose metabolism and insulin sensitivity between FSL and SD rats. Hearts were perfused in a Langendorff model and were subjected or not to IPC before 40 min of global ischaemia, followed by 120 min of reperfusion. Myocardial infarct size was found to be significantly larger in the FSL rats than in the SD rats following I/R injury (62.4+/-4.2 compared with 46.9+/-2.9%; P<0.05). IPC reduced the infarct size (P<0.01) and improved haemodynamic function (P<0.01) in both FSL and SD rats. No significant difference was found in blood glucose levels between the two groups measured after 12 h of fasting, but fasting plasma insulin (70.1+/-8.9 compared with 40.9+/-4.7 pmol/l; P<0.05) and the HOMA (homoeostatic model assessment) index (P<0.01) were significantly higher in FSL rats compared with SD rats. In conclusion, FSL rats had larger infarct sizes following I/R injury and were found to be hyperinsulinaemic compared with SD rats, but appeared to have a maintained cardioprotective mechanism against I/R injury, as IPC reduced infarct size in these rats. This animal model may be useful in future studies when examining the mechanisms that contribute to the cardiovascular complications associated with depression.

  2. Polycythemia vera presenting as acute myocardial infarction: An unusual presentation

    PubMed Central

    Bahbahani, Hussain; Aljenaee, Khaled; Bella, Abdelhaleem

    2014-01-01

    Acute myocardial infarction (AMI) is usually seen in the setting of atherosclerosis and its associated risk factors. Myocardial infarction in the young poses a particular challenge, as the disease is less likely, due to atherosclerosis. We report the case of a 37-year-old female patient who presented with ST segment elevation anterolateral AMI. The only abnormality on routine blood investigation was raised hemoglobin and hematocrit. After further testing, she was diagnosed according to the World Health Organization (WHO) criteria with polycythemia vera. This case illustrates the importance of recognizing polycythemia vera as an important cause of thrombosis, which can present initially as AMI, and to emphasize the early recognition of the disease in order to initiate appropriate management strategies. PMID:25544823

  3. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    PubMed Central

    Garcia, Larissa Ferraz; Mataveli, Fábio D’Aguiar; Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell; Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva

    2015-01-01

    Objective Evaluate the effects of VEGF165 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Methods Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF165 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. Results There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF165. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF165, suggesting greater tissue differentiation. Conclusion The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF165 seems to provide a protective effect in the treatment of acute myocardial infarct. PMID:25993074

  4. Effect of hydroxy safflower yellow A on myocardial apoptosis after acute myocardial infarction in rats.

    PubMed

    Zhou, M X; Fu, J H; Zhang, Q; Wang, J Q

    2015-04-10

    This study aimed to investigate the effect of hydroxy safflower yellow A (HSYA) on myocardial apoptosis after acute myocardial infarction (AMI) in rats. We randomly divided 170 male Wistar rats into 6 groups (N = 23): normal control, sham, control, SY (90 mg/kg), HSYA high-dose (HSYA-H, 40 mg/kg), and HSYA low-dose groups (HSYA-L, 20 mg/kg). Myocardial ischemic injury was induced by ligating the anterior descending coronary artery, and the degree of myocardial ischemia was evaluated using electrocardiography and nitroblue tetrazolium staining. Bax and Bcl-2 expressions in the ischemic myocardium were determined using immunohistochemical analysis. Peroxisome proliferator-activated receptor-γ (PPAR-γ) expression in the myocardium of rats with AMI was determined using reverse transcription-polymerase chain reaction. Compared to rats in the control group, those in the HYSA-H, HSYA-L, and SY groups showed a decrease in the elevated ST segments and an increase in the infarct size. The rats in the drug-treated groups showed a significantly lower percentage of Bax-positive cells and a significantly higher percentage of Bcl-2-positive cells than those in the control group (P < 0.05). Moreover, mRNA expression of PPAR-γ in the ischemic myocardium of rats in the SY, HSYA-L, and HSYA-H groups was significantly lower than that in the control group (P < 0.05). Thus, HSYA and SY can attenuate myocardial ischemia in rats, possibly by increasing the level of Bcl-2/Bax, and PPAR-γ may be not a necessary link in this process.

  5. Impact of microvascular obstruction on semiautomated techniques for quantifying acute and chronic myocardial infarction by cardiovascular magnetic resonance

    PubMed Central

    Bulluck, Heerajnarain; Rosmini, Stefania; Abdel-Gadir, Amna; Bhuva, Anish N; Treibel, Thomas A; Fontana, Marianna; Weinmann, Shane; Sirker, Alex; Herrey, Anna S; Manisty, Charlotte; Moon, James C; Hausenloy, Derek J

    2016-01-01

    Aims The four most promising semiautomated techniques (5-SD, 6-SD, Otsu and the full width half maximum (FWHM)) were compared in paired acute and follow-up cardiovascular magnetic resonance (CMR), taking into account the impact of microvascular obstruction (MVO) and using automated extracellular volume fraction (ECV) maps for reference. Furthermore, their performances on the acute scan were compared against manual myocardial infarct (MI) size to predict adverse left ventricular (LV) remodelling (≥20% increase in end-diastolic volume). Methods 40 patients with reperfused ST segment elevation myocardial infarction (STEMI) with a paired acute (4±2 days) and follow-up CMR scan (5±2 months) were recruited prospectively. All CMR analysis was performed on CVI42. Results Using manual MI size as the reference standard, 6-SD accurately quantified acute (24.9±14.0%LV, p=0.81, no bias) and chronic MI size (17.2±9.7%LV, p=0.88, no bias). The performance of FWHM for acute MI size was affected by the acquisition sequence used. Furthermore, FWHM underestimated chronic MI size in those with previous MVO due to the significantly higher ECV in the MI core on the follow-up scans previously occupied by MVO (82 (75–88)% vs 62 (51–68)%, p<0.001). 5-SD and Otsu were precise but overestimated acute and chronic MI size. All techniques were performed with high diagnostic accuracy and equally well to predict adverse LV remodelling. Conclusions 6-SD was the most accurate for acute and chronic MI size and should be the preferred semiautomatic technique in randomised controlled trials. However, 5-SD, FWHM and Otsu could also be used when precise MI size quantification may be adequate (eg, observational studies). PMID:28008358

  6. Association of Interleukin 8 and Myocardial Recovery in Patients with ST-Elevation Myocardial Infarction Complicated by Acute Heart Failure

    PubMed Central

    Husebye, Trygve; Eritsland, Jan; Arnesen, Harald; Bjørnerheim, Reidar; Mangschau, Arild; Seljeflot, Ingebjørg; Andersen, Geir Øystein

    2014-01-01

    Background No data from controlled trials exists regarding the inflammatory response in patients with de novo heart failure (HF) complicating ST-elevation myocardial infarction (STEMI) and a possible role in the recovery of contractile function. We therefore explored the time course and possible associations between levels of inflammatory markers and recovery of impaired left ventricular function as well as levosimendan treatment in STEMI patients in a substudy of the LEvosimendan in Acute heart Failure following myocardial infarction (LEAF) trial. Methods A total of 61 patients developing HF within 48 hours after a primary PCI-treated STEMI were randomised double-blind to a 25 hours infusion of levosimendan or placebo. Levels of IL-6, CRP, sIL-6R, sgp130, MCP-1, IL-8, MMP-9, sICAM-1, sVCAM-1 and TNF-α were measured at inclusion (median 22 h, interquartile range (IQR) 14, 29 after PCI), on day 1, day 2, day 5 and 6 weeks. Improvement in left ventricular function was evaluated as change in wall motion score index (WMSI) by echocardiography. Results Only circulating levels of IL-8 at inclusion were associated with change in WMSI from baseline to 6 weeks, r = ÷0.41 (p = 0.002). No association, however, was found between IL-8 and WMSI at inclusion or peak troponin T. Furthermore, there was a significant difference in change in WMSI from inclusion to 6 weeks between patients with IL-8 levels below, compared to above median value, ÷0.44 (IQR÷0.57, ÷0.19) vs. ÷0.07 (IQR÷0.27, 0.07), respectively (p<0.0001). Levosimendan did not affect the levels of inflammary markers compared to control. Conclusion High levels of IL-8 in STEMI patients complicated with HF were associated with less improvement in left ventricular function during the first 6 weeks after PCI, suggesting a possible role of IL-8 in the reperfusion-related injury of post-ischemic myocardium. Further studies are needed to confirm this hypothesis. Trial Registration ClinicalTrials.gov NCT00324766

  7. Sex differences in ischemia/reperfusion-induced acute kidney injury are dependent on the renal sympathetic nervous system.

    PubMed

    Tanaka, Ryosuke; Tsutsui, Hidenobu; Ohkita, Mamoru; Takaoka, Masanori; Yukimura, Tokihito; Matsumura, Yasuo

    2013-08-15

    Resistance to ischemic acute kidney injury has been shown to be higher in female rats than in male rats. We found that renal venous norepinephrine overflow after reperfusion played important roles in the development of ischemic acute kidney injury. In the present study, we investigated whether sex differences in the pathogenesis of ischemic acute kidney injury were derived from the renal sympathetic nervous system using male and female Sprague-Dawley rats. Ischemia/reperfusion-induced acute kidney injury was achieved by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function was impaired after reperfusion in both male and female rats; however, renal dysfunction and histological damage were more severe in male rats than in female rats. Renal venous plasma norepinephrine levels after reperfusion were markedly elevated in male rats, but were not in female rats. These sex differences were eliminated by ovariectomy or treatment with tamoxifen, an estrogen receptor antagonist, in female rats. Furthermore, an intravenous injection of hexamethonium (25mg/kg), a ganglionic blocker, 5 min before ischemia suppressed the elevation in renal venous plasma norepinephrine levels after reperfusion, and attenuated renal dysfunction and histological damage in male rats, and ovariectomized and tamoxifen-treated female rats, but not in intact females. Thus, the present findings confirmed sex differences in the pathogenesis of ischemic acute kidney injury, and showed that the attenuation of ischemia/reperfusion-induced acute kidney injury observed in intact female rats may be dependent on depressing the renal sympathetic nervous system with endogenous estrogen.

  8. Magnetic Resonance Imaging (MRI) Analysis of Ischemia/Reperfusion in Experimental Acute Renal Injury.

    PubMed

    Pohlmann, Andreas; Arakelyan, Karen; Seeliger, Erdmann; Niendorf, Thoralf

    2016-01-01

    Imbalance between renal oxygen delivery and demand in the first hours after reperfusion is suggested to be decisive in the pathophysiological chain of events leading to ischemia-induced acute kidney injury. Here we describe blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) for continuous monitoring of the deoxyhemoglobin-sensitive MR parameter T 2* in the renal cortex, outer medulla, and inner medulla of rats throughout renal ischemia/reperfusion (I/R). Changes during I/R are benchmarked against the effects of variations in the fraction of inspired oxygen (hypoxia, hyperoxia). This method may be useful for investigating renal blood oxygenation of rats in vivo under various experimental (patho)physiological conditions.

  9. Spontaneous splenic artery aneurysm rupture: mimicking acute myocardial infarct.

    PubMed

    Zeren, Sezgin; Bayhan, Zülfü; Sönmez, Yalcın; Mestan, Metin; Korkmaz, Mehmet; Kadıoglu, Emine; Ucar, Bercis Imge; Devir, Cigdem; Ekici, Fatih Mehmet; Sanal, Bekir

    2014-12-01

    Spontaneous splenic artery aneurysm (SAA) is a rare but a life-threatening condition. Thus, early diagnoses may increase the chance of survival. A 52-year-old female patient was admitted to the emergency department with a pain that starts from the chest and epigastric region and radiates to back and left arm. The patient prediagnosed as having acute myocardial infarct and was under observation when acute abdomen and hemorrhagic shock developed. After further investigation, the patient was diagnosed as having SAA and has undergone a successful surgery. The patient was fully cured and discharged from the hospital on the seventh postoperative day. The patient originally presented with SAA, although she was primarily observed in the emergency department with acute myocardial infarct diagnosis because of similar symptoms and clinical findings to cardiovascular diseases. When changes in the clinical picture occurred, the patient was reevaluated and had undergone an operation because of SAA rupture. Therefore, physicians should take into consideration of aneurysm rupture in the differential diagnosis of the cardiovascular conditions; otherwise, the patient may lose his/her life.

  10. Holmium:YAG laser angioplasty: treatment of acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Topaz, On

    1993-06-01

    We report our clinical experience with a group of 14 patients who presented with acute myocardial infarction. A holmium:YAG laser was applied to the infarct-related artery. This laser emits 250 - 600 mJ per pulse, with a pulse length of 250 microseconds and repetition rate of 5 Hz. Potential benefits of acute thrombolysis by lasers include the absence of systemic lytic state; a shortened thrombus clearing time relative to using thrombolytics; safe removal of the intracoronary thrombus and facilitation of adjunct balloon angioplasty. Potential clinical difficulties include targeting the obstructive clot and plaque, creation of debris and distal emboli and laser-tissue damage. It is conceivable that holmium:YAG laser can be a successful thrombolytic device as its wave length (2.1 microns) coincides with strong water absorption peaks. Since it is common to find an atherosclerotic plaque located under or distal to the thrombotic occlusion, this laser can also be applied for plaque ablation, and the patient presenting with acute myocardial infarction can clearly benefit from the combined function of this laser system.

  11. Weather fronts and acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Kveton, Vit

    1991-03-01

    Some methodological aspects are discussed of the investigation of acute infarct myocarditis (AIM) in relation to weather fronts. Results of a new method of analysis are given. Data were analysed from about the hour of the onset of symptoms, and led to the diagnosis of AIM either immediately or within a few hours or days (3019 cases observed over 4.5 years during 1982 1986 in Plzen, Czechoslovakia). Weather classification was based on three factors (the type of the foregoing front, the type of the subsequent front, the time section of the time interval demarcated by the passage of the surfaces of the fronts). AIM occurrence increased in particular types of weather fronts: (i) by 30% during 7 12 h after a warm front, if the time span between fronts exceeded 24 h; (ii) by 10% in time at least 36 h distant from the foregoing cold or occlusion front and from the succeeding warm or occlusion front; (iii) by 20% during 0 2 h before the passage of the front, provided the foregoing front was not warm and the interval between fronts exceeded 5 h. AIM occurrence decreased by 15% 20% for time span between fronts > 24 h at times 6 11, 6 23 and 6 35 h before a coming warm or occlusion front (for interfrontal intervals 25 48, 49 72 and possibly > 72 h), and also at 12 23 and possibly 12 35 h before a cold front (for intervals 49 72 and possibly > 72 h), if the foregoing front was cold or an occlusion front.

  12. Body Mass Index and Mortality in Acute Myocardial Infarction Patients

    PubMed Central

    Bucholz, Emily M.; Rathore, Saif S.; Reid, Kimberly J.; Jones, Philip G.; Chan, Paul S.; Rich, Michael W.; Spertus, John A.; Krumholz, Harlan M.

    2012-01-01

    Background Previous studies have described an “obesity paradox” with heart failure, whereby higher body mass index (BMI) is associated with lower mortality. However, little is known about the impact of obesity on survival after acute myocardial infarction. Methods Data from 2 registries of patients hospitalized in the United States with acute myocardial infarction between 2003–04 (PREMIER) and 2005–08 (TRIUMPH) were used to examine the association of BMI with mortality. Patients (n=6359) were categorized into BMI groups (kg/m2) using baseline measurements. Two sets of analyses were performed using Cox proportional hazards regression with fractional polynomials to model BMI as categorical and continuous variables. To assess the independent association of BMI with mortality, analyses were repeated adjusting for 7 domains of patient and clinical characteristics. Results Median BMI was 28.6. BMI was inversely associated with crude 1-year mortality (normal, 9.2%; overweight, 6.1%; obese, 4.7%; morbidly obese; 4.6%; p<0.001), which persisted after multivariable adjustment. When BMI was examined as a continuous variable, the hazards curve declined with increasing BMI and then increased above a BMI of 40. Compared with patients with a BMI of 18.5, patients with higher BMIs had a 20% to 68% lower mortality at 1 year. No interactions between age (p=0.37), gender (p=0.87) or diabetes mellitus (p=0.55) were observed. Conclusions There appears to be an “obesity paradox” among acute myocardial infarction patients such that higher BMI is associated with lower mortality, an effect that was not modified by patient characteristics and was comparable across age, gender, and diabetes subgroups. PMID:22483510

  13. Schisandrin B protects myocardial ischemia-reperfusion injury partly by inducing Hsp25 and Hsp70 expression in rats.

    PubMed

    Chiu, Po Yee; Ko, Kam Ming

    2004-11-01

    Schisandrin B (Sch B) is a hepato- and cardioprotective ingredient isolated from the fruit of Schisandra chinensis, a traditional Chinese herb clinically used to treat viral and chemical hepatitis. In order to investigate whether the induction of heat shock protein (Hsp)25 and Hsp70 expression plays a role in the cardioprotection afforded by Sch B pre-treatment against ischemia-reperfusion (I-R) injury, the time-course of myocardial Hsp25 and Hsp70 expression was examined in Sch B-pre-treated rats. Sch B pre-treatment (1.2 mmol/kg) produced time-dependent increases in Hsp25 and Hsp70 expression in rat hearts, with the maximum enhancement observable at 48 and 72 h post-dosing, respectively. Buthionine sulfoximine/phorone treatment, while abolishing the beneficial effect of Sch B on mitochondrial glutathione redox status, did not completely abrogate the cardioprotection against I-R injury. Heat shock treatment could increase myocardial Hsp25 and Hsp70 expression and protect against I-R injury under the present experimental conditions. The results indicate that the induction of Hsp25 and Hsp70 expression contributes at least partly to the cardioprotection afforded by Sch B pre-treatment against I-R injury.

  14. Hydroxysafflor yellow A alleviates myocardial ischemia/reperfusion in hyperlipidemic animals through the suppression of TLR4 signaling

    PubMed Central

    Han, Dan; Wei, Jie; Zhang, Rui; Ma, Wenhuan; Shen, Chen; Feng, Yidong; Xia, Nian; Xu, Dan; Cai, Dongcheng; Li, Yunman; Fang, Weirong

    2016-01-01

    Hyperlipidemia aggravates myocardial ischemia/reperfusion (MI/R) injury through stimulating excessive inflammatory response. Therefore, blockade of inflammatory signal is a potential therapeutic management for MI/R complicated with hyperlipidemia. Hydroxysafflor yellow A (HSYA, a monomer extracted from Carthamus tinctorius L.), was studied in this article to address that the regulation of inflammatory signal would alleviate MI/R combined with hyperlipidemia injury. High-fat diet induced hyperlipidemia worsened MI/R mediated heart injury (elevation of infarct size, CK-MB and LDH activity), activated TLR4 over-expression in hearts, released inflammatory cytokines (LPS, TNF-α and IL-1β) excessively. HSYA administration suppressed the over-expression of TLR4 and alleviated heart damage caused by MI/R complicated with hyperlipidemia. Furthermore, HSYA had little influence on MI/R injury in TLR4-knockout mice, which indicated that HSYA protected MI/R through TLR4 inhibition. In vitro, hypoxia/reoxygenation (H/R) coexisting with LPS model in neonatal rat ventricular myocytes (NRVMs) induced serious damage compared with H/R injury to NRVMs. HSYA decreased excessive secretion of inflammatory cytokines, down-regulated over-expression of TLR4 and NF-κB in H/R + LPS injured NRVMs. In conclusion, HSYA alleviated myocardial inflammatory injury through suppressing TLR4, offering an alternative medication for MI/R associated with hyperlipidemia. PMID:27731393

  15. Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor gamma-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury.

    PubMed

    Takaya, Norihide; Katoh, Youichi; Iwabuchi, Kazuhisa; Hayashi, Ichiro; Konishi, Hakuoh; Itoh, Seigo; Okumura, Ko; Ra, Chisei; Nagaoka, Isao; Daida, Hiroyuki

    2005-12-01

    Platelet activation and the formation of platelet microaggregates in coronary vessels play pivotal roles in myocardial ischemia and reperfusion injury. The Fc receptor gamma-chain (FcR gamma) is coexpressed with glycoprotein (GP) VI, forming a platelet collagen receptor, and the activation of platelets by collagen is closely coupled with tyrosine phosphorylation of the FcRgamma. To examine the functional significance of platelet FcR gamma/GPVI complex in the early phase of myocardial ischemia and reperfusion injury in mice, we performed coronary occlusion and reperfusion experiments using wild type mice and FcRgamma-deficient (FcRgamma(-/-)) mice that lack GPVI. The infarct size was significantly smaller in FcRgamma(-/-) mice subjected to occlusion and reperfusion of the coronary artery than in control FcR gamma(+/+) mice. Twenty-four hours after the reperfusion, electron microscopy of the injured tissue showed substantially more platelet aggregation and occlusive platelet microthrombi in the capillaries of the damaged areas of the wild type mice than in those of the FcR gamma(-/-) mice. Platelet Syk was scarcely activated in the FcR gamma(-/-) mice after myocardial ischemia and reperfusion, but significantly activated in the FcR gamma(+/+) mice. CD11b expression on neutrophils was elevated after myocardial ischemia and reperfusion in both mouse groups, whereas myeloperoxidase activity in the injured areas was significantly lower in the FcRgamma(-/-) mice than in the FcRgamma(+/+) mice. These results suggest that the collagen-induced activation of platelets through the FcR gamma plays a pivotal role in the extension of myocardial ischemia-reperfusion injury. FcRgamma and GPVI may be important therapeutic targets for myocardial ischemia-reperfusion injury.

  16. Novel, selective EPO receptor ligands lacking erythropoietic activity reduce infarct size in acute myocardial infarction in rats.

    PubMed

    Kiss, Krisztina; Csonka, Csaba; Pálóczi, János; Pipis, Judit; Görbe, Anikó; Kocsis, Gabriella F; Murlasits, Zsolt; Sárközy, Márta; Szűcs, Gergő; Holmes, Christopher P; Pan, Yijun; Bhandari, Ashok; Csont, Tamás; Shamloo, Mehrdad; Woodburn, Kathryn W; Ferdinandy, Péter; Bencsik, Péter

    2016-11-01

    Erythropoietin (EPO) has been shown to protect the heart against acute myocardial infarction in pre-clinical studies, however, EPO failed to reduce infarct size in clinical trials and showed significant safety problems. Here, we investigated cardioprotective effects of two selective non-erythropoietic EPO receptor ligand dimeric peptides (AF41676 and AF43136) lacking erythropoietic activity, EPO, and the prolonged half-life EPO analogue, darbepoetin in acute myocardial infarction (AMI) in rats. In a pilot study, EPO at 100U/mL significantly decreased cell death compared to vehicle (33.8±2.3% vs. 40.3±1.5%, p<0.05) in rat neonatal cardiomyocytes subjected to simulated ischemia/reperfusion. In further studies (studies 1-4), in vivo AMI was induced by 30min coronary occlusion and 120min reperfusion in male Wistar rats. Test compounds and positive controls for model validation (B-type natriuretic peptide, BNP or cyclosporine A, CsA) were administered iv. before the onset of reperfusion. Infarct size (IS) was measured by standard TTC staining. In study 1, 5000U/kg EPO reduced infarct size significantly compared to vehicle (45.3±4.8% vs. 59.8±4.5%, p<0.05). In study 2, darbepoetin showed a U-shaped dose-response curve with maximal infarct size-reducing effect at 5μg/kg compared to the vehicle (44.4±5.7% vs. 65.9±2.7%, p<0.01). In study 3, AF41676 showed a U-shaped dose-response curve, where 3mg/kg was the most effective dose compared to the vehicle (24.1±3.9% vs. 44.3±2.5%, p<0.001). The positive control BNP significantly decreased infarct size in studies 1-3 by approximately 35%. In study 4, AF43136 at 10mg/kg decreased infarct size, similarly to the positive control CsA compared to the appropriate vehicle (39.4±5.9% vs. 58.1±5.4% and 45.9±2.4% vs. 63.8±4.1%, p<0.05, respectively). This is the first demonstration that selective, non-erythropoietic EPO receptor ligand dimeric peptides AF41676 and AF43136 administered before reperfusion are able to reduce

  17. Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction (EXAMI): study protocol for a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Myocardial infarction causes irreversible loss of cardiomyocytes and may lead to loss of ventricular function, morbidity and mortality. Infarct size is a major prognostic factor and reduction of infarct size has therefore been an important objective of strategies to improve outcomes. In experimental studies, glucagon-like peptide 1 and exenatide, a long acting glucagon-like peptide 1 receptor agonist, a novel drug introduced for the treatment of type 2 diabetes, reduced infarct size after myocardial infarction by activating pro-survival pathways and by increasing metabolic efficiency. Methods The EXAMI trial is a multi-center, prospective, randomized, placebo controlled trial, designed to evaluate clinical outcome of exenatide infusion on top of standard treatment, in patients with an acute myocardial infarction, successfully treated with primary percutaneous coronary intervention. A total of 108 patients will be randomized to exenatide (5 μg bolus in 30 minutes followed by continuous infusion of 20 μg/24 h for 72 h) or placebo treatment. The primary end point of the study is myocardial infarct size (measured using magnetic resonance imaging with delayed enhancement at 4 months) as a percentage of the area at risk (measured using T2 weighted images at 3-7 days). Discussion If the current study demonstrates cardioprotective effects, exenatide may constitute a novel therapeutic option to reduce infarct size and preserve cardiac function in adjunction to reperfusion therapy in patients with acute myocardial infarction. Trial registration ClinicalTrials.gov: NCT01254123 PMID:22067476

  18. Cilostazol protects the heart against ischaemia reperfusion injury in a rabbit model of myocardial infarction: focus on adenosine, nitric oxide and mitochondrial ATP-sensitive potassium channels.

    PubMed

    Bai, Yushan; Muqier; Murakami, Hiroya; Iwasa, Masamitsu; Sumi, Shohei; Yamada, Yoshihisa; Ushikoshi, Hiroaki; Aoyama, Takuma; Nishigaki, Kazuhiko; Takemura, Genzou; Uno, Bunji; Minatoguchi, Shinya

    2011-10-01

    1. The present study examined whether or not cilostazol reduces the myocardial infarct size, and investigated its mechanism in a rabbit model of myocardial infarction. 2. Japanese white rabbits underwent 30 min of coronary occlusion, followed by 48 h of reperfusion. Cilostazol (1 and 5 mg/kg) or vehicle was given intravenously 5 min before ischaemia. 8-p-sulfophenyl theophylline (8SPT; an adenosine receptor blocker, 7.5 mg/kg), Nω-nitro-L-arginine methylester (l-NAME; an NOS inhibitor, 10 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD; a mitochondrial ATP-sensitive potassium (KATP) channel blocker, 5 mg/kg) was given intravenously 5 min before cilostazol injection. Infarct size was determined as a percentage of the risk area. 3. The myocardial interstitial levels of adenosine and nitrogen oxide (NOx) during ischaemia and reperfusion, and the intensity of myocardial dihydroethidium staining were determined. 4. Infarct size was significantly reduced in the cilostazol 1 mg/kg (38.4% (2.9%)) and cilostazol 5 mg/kg (30.7% (4.7%)) groups compared with that in the control group (46.5% (4.2%)). The infarct size-reducing effect of cilostazol was completely abolished by 8SPT (46.6% (3.5%)), L-NAME (49.0% (5.5%)), or 5HD (48.5% (5.1%)). 8SPT, L-NAME or 5HD alone did not affect the infarct size. Cilostazol treatment significantly increased myocardial levels of adenosine and NOx during ischaemia, and attenuated the intensity of dihydroethidium staining during reperfusion. 5. These findings show that cilostazol reduces the myocardial infarct size by increasing adenosine and NOx levels, attenuating superoxide production and opening the mitochondrial KATP channels. Cilostazol might provide a new strategy for the treatment of coronary heart disease.

  19. Serum creatine kinase B subunit activity in diagnosis of acute myocardial infarction.

    PubMed Central

    Ljungdahl, L; Gerhardt, W; Hofvendahl, S

    1980-01-01

    The value of serum creatine kinase B subunit activity (CK B) in the diagnosis of acute myocardial infarction was studied in 238 consecutive cases. All were admitted to a coronary care unit because of suspected acute myocardial infarction. Serum CK B activity was determined by an immunoinhibition procedure, using a CK M subunit inhibiting antibody (anti-M). For the evaluation of serum CK B, patients were classified into acute myocardial infarction and non-acute myocardial infarction groups. This classification was based on electrocardiographic findings, on quantitative determinations of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total serum creatine kinase (CK) activities, and on qualitative electrophoretic determinations of serum CK and serum lactate dehydrogenase (LD) isoenzymes. The prevalence of acute myocardial infarction in the patient material was 0.47. Serum CK B subunit activity was found to be a highly selective indicator of acute myocardial infarction with a predictive value of a positive test result of 0.97 and a predictive value of a negative test result of 0.99. The serum CK B activity increased above the acute myocardial infarction discrimination limit within 12 hours from onset of symptoms. Two non-acute myocardial infarction patients, who were resuscitated after cardiac arrest, had increased serum CK B values caused by the transient presence of CK isoenzyme BB in serum. PMID:7378210

  20. Comparative Prognostic Utility of Indexes of Microvascular Function Alone or in Combination in Patients With an Acute ST-Segment–Elevation Myocardial Infarction

    PubMed Central

    Carrick, David; Haig, Caroline; Ahmed, Nadeem; Carberry, Jaclyn; Yue May, Vannesa Teng; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Lindsay, Mitchell; Hood, Stuart; Watkins, Stuart; Davie, Andrew; Mahrous, Ahmed; Mordi, Ify; Ford, Ian; Radjenovic, Aleksandra; Oldroyd, Keith G.

    2016-01-01

    Background: Primary percutaneous coronary intervention is frequently successful at restoring coronary artery blood flow in patients with acute ST-segment–elevation myocardial infarction; however, failed myocardial reperfusion commonly passes undetected in up to half of these patients. The index of microvascular resistance (IMR) is a novel invasive measure of coronary microvascular function. We aimed to investigate the pathological and prognostic significance of an IMR>40, alone or in combination with a coronary flow reserve (CFR≤2.0), in the culprit artery after emergency percutaneous coronary intervention for acute ST-segment–elevation myocardial infarction. Methods: Patients with acute ST-segment–elevation myocardial infarction were prospectively enrolled during emergency percutaneous coronary intervention and categorized according to IMR (≤40 or >40) and CFR (≤2.0 or >2.0). Cardiac magnetic resonance imaging was acquired 2 days and 6 months after myocardial infarction. All-cause death or first heart failure hospitalization was a prespecified outcome (median follow-up, 845 days). Results: IMR and CFR were measured in the culprit artery at the end of percutaneous coronary intervention in 283 patients with ST-segment–elevation myocardial infarction (mean±SD age, 60±12 years; 73% male). The median IMR and CFR were 25 (interquartile range, 15–48) and 1.6 (interquartile range, 1.1–2.1), respectively. An IMR>40 was a multivariable associate of myocardial hemorrhage (odds ratio, 2.10; 95% confidence interval, 1.03–4.27; P=0.042). An IMR>40 was closely associated with microvascular obstruction. Symptom-to-reperfusion time, TIMI (Thrombolysis in Myocardial Infarction) blush grade, and no (≤30%) ST-segment resolution were not associated with these pathologies. An IMR>40 was a multivariable associate of the changes in left ventricular ejection fraction (coefficient, −2.12; 95% confidence interval, −4.02 to −0.23; P=0.028) and left ventricular

  1. Postmortem diagnosis of acute myocardial infarction in patients with acute respiratory failure - demographics, etiologic and pulmonary histologic analysis

    PubMed Central

    de Matos Soeiro, Alexandre; Ruppert, Aline D; Canzian, Mauro; Capelozzi, Vera L; Serrano, Carlos V

    2012-01-01

    OBJECTIVES: Acute respiratory failure is present in 5% of patients with acute myocardial infarction and is responsible for 20% to 30% of the fatal post-acute myocardial infarction. The role of inflammation associated with pulmonary edema as a cause of acute respiratory failure post-acute myocardial infarction remains to be determined. We aimed to describe the demographics, etiologic data and histological pulmonary findings obtained through autopsies of patients who died during the period from 1990 to 2008 due to acute respiratory failure with no diagnosis of acute myocardial infarction during life. METHODS: This study considers 4,223 autopsies of patients who died of acute respiratory failure that was not preceded by any particular diagnosis while they were alive. The diagnosis of acute myocardial infarction was given in 218 (4.63%) patients. The age, sex and major associated diseases were recorded for each patient. Pulmonary histopathology was categorized as follows: diffuse alveolar damage, pulmonary edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds ratio of acute myocardial infarction associated with specific histopathology was determined by logistic regression. RESULTS: In total, 147 men were included in the study. The mean age at the time of death was 64 years. Pulmonary histopathology revealed pulmonary edema as well as the presence of diffuse alveolar damage in 72.9% of patients. Bacterial bronchopneumonia was present in 11.9% of patients, systemic arterial hypertension in 10.1% and dilated cardiomyopathy in 6.9%. A multivariate analysis demonstrated a significant positive association between acute myocardial infarction with diffuse alveolar damage and pulmonary edema. CONCLUSIONS: For the first time, we demonstrated that in autopsies of patients with acute respiratory failure as the cause of death, 5% were diagnosed with acute myocardial infarction. Pulmonary histology revealed a significant inflammatory response, which has

  2. Clinical benefit of adenosine as an adjunct to reperfusion in ST-elevation myocardial infarction patients: An updated meta-analysis of randomized controlled trials

    PubMed Central

    Bulluck, Heerajnarain; Sirker, Alex; Loke, Yoon K.; Garcia-Dorado, David; Hausenloy, Derek J.

    2016-01-01

    Background Adenosine administered as an adjunct to reperfusion can reduce coronary no-reflow and limit myocardial infarct (MI) size in ST-segment elevation myocardial infarction (STEMI) patients. Whether adjunctive adenosine therapy can improve clinical outcomes in reperfused STEMI patients is not clear and is investigated in this meta-analysis of 13 randomized controlled trials (RCTs). Methods We performed an up-to-date search for all RCTs investigating adenosine as an adjunct to reperfusion in STEMI patients. We calculated pooled relative risks using a fixed-effect meta-analysis assessing the impact of adjunctive adenosine therapy on major clinical endpoint including all-cause mortality, non-fatal myocardial infarction, and heart failure. Surrogate markers of reperfusion were also analyzed. Results 13 RCTs (4273 STEMI patients) were identified and divided into 2 subgroups: intracoronary adenosine versus control (8 RCTs) and intravenous adenosine versus control (5 RCTs). In patients administered intracoronary adenosine, the incidence of heart failure was significantly lower (risk ratio [RR] 0.44 [95% CI 0.25–0.78], P = 0.005) and the incidence of coronary no-reflow was reduced (RR for TIMI flow<3 postreperfusion 0.68 [95% CI 0.47–0.99], P = 0.04). There was no difference in heart failure incidence in the intravenous adenosine group but most RCTs in this subgroup were from the thrombolysis era. There was no difference in non-fatal MI or all-cause mortality in both subgroups. Conclusion We find evidence of improved clinical outcome in terms of less heart failure in STEMI patients administered intracoronary adenosine as an adjunct to reperfusion. This finding will need to be confirmed in a large adequately powered prospective RCT. PMID:26402450

  3. Reperfusion Therapies for Acute Ischemic Stroke: An Update

    PubMed Central

    Dorado, Laura; Millán, Mònica; Dávalos, Antoni

    2014-01-01

    Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke. PMID:24646159

  4. Reperfusion therapies for acute ischemic stroke: an update.

    PubMed

    Dorado, Laura; Millán, Mònica; Dávalos, Antoni

    2014-11-01

    Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke.

  5. Acute non-Q-wave myocardial infarction: a distinct clinical entity of increasing importance.

    PubMed Central

    Montague, T J; MacKenzie, B R; Henderson, M A; Macdonald, R G; Forbes, C J; Chandler, B M

    1988-01-01

    Despite the increasing incidence of acute non-Q-wave myocardial infarction, controversy remains regarding its validity as a distinct pathophysiologic physiologic and clinical entity. Review of the data indicates that the controversy is more apparent than real. The pathophysiologic factor discriminating best between non-Q-wave and Q-wave infarction is the incidence rate of total occlusion of the infarct-related artery, approximately 30% in non-Q-wave infarction and 80% in Q-wave infarction. Patients with non-Q-wave infarction have a higher incidence of pre-existing angina than patients with Q-wave infarction; they also have lower peak creatine kinase levels, higher ejection fractions and lower wall-motion abnormality scores, which suggests a smaller area of acute infarction damage. However, patients with non-Q-wave infarction have a significantly shorter time to peak creatine kinase level and more heterogeneous ventriculographic and electrocardiographic infarct patterns. The in-hospital death rate is lower in non-Q-wave than in Q-wave infarction (approximately 12% v. 19%). The long-term death rates are similar for the two groups (27% and 23%), but the incidence of subsequent coronary events is higher among patients with non-Q-wave infarction; in particular, reinfarction is an important predictor of risk of death. Most of the differences in biologic and clinical variables between the two types of acute infarction can be related to a lower incidence of total occlusion, earlier reperfusion or better collateral supply in non-Q-wave infarction. Further study is needed to better characterize the long-term risk and to define the most appropriate therapies. PMID:3044553

  6. Activated platelet chemiluminescence and presence of CD45+ platelets in patients with acute myocardial infarction.

    PubMed

    Gabbasov, Zufar; Ivanova, Oxana; Kogan-Yasny, Victor; Ryzhkova, Evgeniya; Saburova, Olga; Vorobyeva, Inna; Vasilieva, Elena

    2014-01-01

    It has been found that in 15% of acute myocardial infarction patients' platelets generate reactive oxygen species that can be detected with luminol-enhanced chemiluminescence of platelet-rich plasma within 8-10 days after acute myocardial infarction. This increase in generate reactive oxygen species production coincides with the emergence of CD45(+) platelets. The ability of platelets to carry surface leukocyte antigen implies their participation in exchange of specific proteins in the course of acute myocardial infarction. Future studies of CD45(+) platelets in peripheral blood of acute myocardial infarction patients in association with generate reactive oxygen species production may provide a new insight into the complex mechanisms of cell-cell interactions associated with acute myocardial infarction.

  7. [The measurement of CoQ10 in the acute phase of a myocardial infarct].

    PubMed

    Puletti, M; Trappolini, M; Di Palma, A; Curione, M; Schiavone, R A; Matteoli, S; Borgia, C

    1991-05-01

    The authors have studied the behaviour of ubidecorenone (Co Q10) in the acute phase of myocardial infarction in 24 patients, 19 male and 5 female, mean age 56.8 +/- 3.3. Ubidecorenone level was determined on admittance, after 48 hours and on the 7th and 30th days. A significant decrease was observed from the first to the 3rd day (mean values 0.90 +/- 0.18 microgram/ml vs 0.72 +/- 0.22, p less than 0.01). Thereafter a progressive rise was observed, but at the 30th day mean values were still below the basal ones. No significant differences were observed between patients treated with fibrinolytic agents and those not so treated, nor between those in whom reperfusion was obtained and the others. Nor was there a proven correlation with changes in creatinkinase. The behaviour of ubidecorenone may be associated with increased consumption for metabolic needs and increased destruction in scavenger action, and also to a lesser extent to decreased production due to lower food intake.

  8. Sudden death due to ventricular double rupture as a complication of inferior acute myocardial infarction

    PubMed Central

    Chen, Shi-Jian; Zhang, Chen; Meng, Qing-Tao; Peng, Yong; Chen, Mao

    2016-01-01

    Abstract Rationale: Ventricular double rupture (VDR) is a rare but lethal mechanical complication of acute myocardial infarction (AMI). The early identification and timely treatment of VDR remain challenging problems. We present a case of AMI with VDR and briefly review the characteristics and prognosis of this life-threatening disease. Patient concerns and Diagnoses: A 77-year-old male presented to our hospital with a 4-day history of severe dizziness, mild chest tightness, and dyspnea. An inferior AMI was diagnosed. Interventions and Outcomes: On the second hospital day, hypotension and a new cardiac murmur was found. The emergency echocardiographic study disclosed a ventricular septal defect. Soon after that the patient suddenly died of ventricular free-wall rupture. Lessons: In patients with AMI complicated by a septal perforation in the apical region, close to the septum-free wall junction, special attention should be paid to the great risk of VDR. Other high risk factors included advanced age, delayed reperfusion, and inferior infarction. Sufficient evaluation of the risk factors, close monitoring of vital signs, early identification of the specific symptoms, and timely treatment are the key points for the effective prediction and prevention of VDR. PMID:28033290

  9. Potential beneficial mechanisms of insulin (glucose-potassium) in acute myocardial infarction

    PubMed Central

    van der Horst, I.C.C.; Zijlstra, F.

    2005-01-01

    In the time-span of almost a century, a large amount of experimental evidence has been accumulated that underlines the importance of glucose metabolism during ischaemia/reperfusion of the heart. As early as 1912, Goulston suggested that treatment with glucose could be beneficial in several heart diseases. The first experimental results on the mechanical effects of insulin and glucose in the isolated heart were reported by Visscher and Muller in 1926. In 1935, Evans and colleagues showed that the uptake of glucose is increased in the ischaemic myocardium. Almost 30 years later, Sodi-Pallares and colleagues suggested that metabolic interference during myocardial ischaemia with GIK infusion decreased electrocardiographic signs of ischaemia. They also showed that glucose-insulin-potassium (GIK) infusion resulted in a lower occurrence of arrhythmias. They attributed this effect mainly to the influx of potassium in ischaemic cardiomyocytes. In order to further stimulate potassium transport into the cell, insulin was administered. Consequently, the rise of intercellular calcium is curtailed by the influx of potassium and so the incidence of arrhythmias is reduced. However, systemic infusion of insulin stimulates the uptake of glucose in many celltypes, which may result in hypoglycaemic episodes. Consequently, it is not possible to administer potassium and insulin in high concentrations without adding glucose. Interventions in the glucose metabolism in the clinical arena, whether or not used to correct acute hyperglycaemia, encompass three potentially effective elements: glucose, insulin and potassium. PMID:25696497

  10. A quantitative analysis of the effect of glucose-insulin-potassium in acute myocardial infarction

    PubMed Central

    Rasoul, S.; Svilaas, T.; Ottervanger, J-P.; Timmer, J.R.; van 't Hof, A.W.J.; Zijlstra, F.

    2006-01-01

    Objective To review the currently available data to investigate the clinical benefit of high- and low-dose glucose-insulin-potassium (GIK) in patients with ST-segment elevation acute myocardial infarction (STEMI). Design Quantitative analysis of all randomised trials on GIK in patients with STEMI. Electronic and manual searches for randomised controlled trials of GIK in STEMI were performed with regard to inclusion criteria, dose of GIK and additional use of reperfusion therapy, and a meta-analysis with the primary endpoint 30-day mortality was performed. Patients Data from 16 randomised trials, involving 26,273 patients, were included. Results Studies were conducted between 1962 and 2005. Overall, hospital mortality was 9.6% after GIK compared with 10.2% in controls (p=0.088). GIK infusion was not associated with an increase in major adverse events. Conclusion This quantitative analysis of GIK in patients with STEMI did not show a beneficial or detrimental effect of GIK infusion on 30-day mortality. GIK infusion should not be part of the standard therapy for patients with STEMI. PMID:25696550

  11. [Venous treatment with streptase in acute myocardial infarct and unstable stenocardia (a new method)].

    PubMed

    Atanasov, K; Dzhurdzhev, A; Kichukov, N; Ivanov, I; Mineva, Zh

    1987-01-01

    Streptokinase treatment was carried out in the intensive care unit of III Internal Clinic, the Higher Medical Institute--Plovdiv, on 54 patients, 51 of them with acute myocardial infarction (AMI) and 3 with intermediary coronary syndrome, making use of the preparations streptase (GFR) and avelysin (GDR). A control group of 35 patients with AMI was used. The treatment was initiated with stream administration of heparin 10,000 U and urbazon 20 mg, whereafter streptokinase 1,250,000 U per 1 h was included on that background. The results were determined according to ECG in 30 leads, recorded by 2, 4, 6, 12 and 24 h, according to creatine-phosphokinase activity and the outcome of the disease. The treatment was uninterrupted up to 24 h with the determination of the individual fibrinolytic activity. Normalization of S-T segment was established by 4 h with restoration of ECG in 10 patients, and in the rest--maintaining QS or QR forms. Re-perfusion arrhythmias were observed in 66.67% and data about re-thrombosis--in 13.61%. Lethality was 5.89%. The method is emphasized to be a reliable means for the treatment of AMI.

  12. Meta-analysis of remote ischemic conditioning in patients with acute myocardial infarction

    PubMed Central

    Man, Changfeng; Gong, Dandan; Zhou, Yongjing; Fan, Yu

    2017-01-01

    Effects of remote ischemic conditioning (RIC) in acute myocardial infarction (AMI) patients remain conflicting. We performed this meta-analysis of randomized clinical trials (RCTs) to evaluate the benefits of the RIC in patients with AMI. Potentially relevant RCTs were identified by searching PubMed, Embase, Cochrane Library, VIP, CNKI, and Wanfang database until November 2016. RCTs evaluating RIC using intermittent limb ischemia-reperfusion in AMI patients were included. Thirteen RCTs were identified and analyzed. Meta-analysis showed that RIC significantly reduced the area under the curve (AUC) of creatine kinase-myocardial band (CK-MB) (standardized mean difference [SMD] −0.29; 95% confidence intervals [CI] −0.44 to −0.14; P = 0.0002) and AUC of troponin T (SMD −0.22; 95% CI −0.37 to −0.08; P = 0.003). Risk ratio (RR) for ≥70% ST-segment resolution favored RIC group than the control group (RR 1.39; 95% CI 1.03–1.86; P = 0.03). RIC also significantly reduced all-cause mortality (RR 0.33; 95%CI 0.17–0.64; P = 0.001). Subgroup analyses on the CK-MB AUC and ST-segment resolution ≥70% rate showed that the effects of RIC appeared to be affected by the limb used, duration of RIC, and clinical setting. RIC may offer cardioprotective effects by improving ST-segment resolution and reducing the infarct size in AMI patients. PMID:28272470

  13. Protective mechanism of quercetin on acute myocardial infarction in rats.

    PubMed

    Li, B; Yang, M; Liu, J W; Yin, G T

    2016-03-11

    To investigate the protective mechanism of quercetin on acute myocardial infarction (AMI) rats, an AMI rat model was established by ligating the left coronary anterior descending branch. The rats were randomly divided into the model group and low- and high-dose quercetin groups. The control group comprised sham-operated rats. The rats in the low- and high-dose quercetin groups were administered 100 and 400 mg/kg quercetin, respectively, by gavage. The rats in the control and model groups were administered isometric normal saline once daily for one week. The mRNA and protein levels of TNF-α and IL-1β in the myocardial tissue of rats were detected in each group by real time polymerase chain reaction and enzyme-linked immunosorbent assay. Malondialdehyde (MDA) content in the myocardial tissue and superoxide dismutase (SOD) and catalase (CAT) activities were detected using a colorimetric method. The level of apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. Compared with those in the control group, the mRNA and protein levels of TNF-α, IL-1β and MDA content in the model, low-, and high-dose groups significantly increased. SOD and CAT activities decreased significantly. The cell apoptosis index increased significantly  (P < 0.05). Compared with those in the model group, the mRNA and protein levels of TNF-α and IL-1β and MDA content in myocardial tissue of rats in the low-dose and high-dose groups decreased significantly. SOD and CAT activities increased significantly. The cell apoptosis index significantly reduced (P < 0.05). In conclusion, quercetin has significant anti-inflammatory, antioxidant, and anti-apoptotic effects on AMI rats and can effectively protect against myocardium damage.

  14. Effects of selective phosphodiesterase-5-inhibition on myocardial contractility and reperfusion injury after heart transplantation.

    PubMed

    Loganathan, Sivakkanan; Radovits, Tamás; Hirschberg, Kristóf; Korkmaz, Sevil; Barnucz, Eniko; Karck, Matthias; Szabó, Gábor

    2008-11-27

    Recently, the infarct reducing and cardioprotective effects of phosphodiesterase-5-inhibitors were described. In this study, we investigated these effects on ischemia/reperfusion injury in a rat model of heart transplantation. Three groups were assigned for our study: a vardenafil preconditioning group, an ischemic control, and a nonischemic control. Hemodynamic parameters were significantly increased in the vardenafil group (Pmax: 82+/-4 vs. 110+/-12 vs. 127+/-13 mm Hg; dP/dtmax: 1740+/-116 vs. 3197+/-599 vs. 4397+/-602 mm Hg/sec; ischemic control vs. vardenafil vs. nonischemic control; P<0.05 vs. ischemic control). Furthermore, we recorded increased ATP levels and significantly less apoptosis in the treatment group after terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (apoptosis index: 27.23%+/-1.54% vs. 16.77%+/-1.42% vs. 18.86%+/-1.07%; ischemic control vs. vardenafil vs. nonischemic control; P<0.05 vs. ischemic control). Our current results support the concept that the cGMP-PKG-pathway plays an important role in ischemia/reperfusion injury. We could show that up-regulating this pathway has a preconditioning-like effect and can effectively reduce ischemia/reperfusion injury.

  15. Stem cell mobilisation by granulocyte-colony stimulating factor in patients with acute myocardial infarction. Long-term results of the REVIVAL-2 trial.

    PubMed

    Steppich, Birgit; Hadamitzky, Martin; Ibrahim, Tareq; Groha, Philip; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Kastrati, Adnan; Ott, Ilka

    2016-04-01

    Treatment with granulocyte-colony stimulating factor (G-CSF) mobilises cells from the bone marrow to the peripheral blood. Previous preclinical and early clinical trials may suggest that treatment with G-CSF leads to improved myocardial perfusion and function in acute or chronic ischaemic heart disease. In the REVIVAL-2 study we found that stem cell mobilisation by G-CSF does not influence infarct size, left ventricular function and coronary restenosis in patients with acute myocardial infarction (MI) that underwent successful percutaneous coronary intervention. The objective of the present analysis was to assess the impact of G-CSF treatment on seven-year clinical outcomes from the REVIVAL-2 trial. In the randomized, double-blind, placebo-controlled REVIVAL-2 study, 114 patients with the diagnosis of acute myocardial infarction were enrolled five days after successful reperfusion by percutaneous coronary intervention. Patients were assigned to receive 10 µg/kg G-CSF (n=56) or placebo (n=58) for five days. The primary endpoint for this long-term outcome analysis was the composite of death, myocardial infarction or stroke seven years after randomisation. The endpoint occurred in 14.3 % of patients in the G-CSF group versus 17.2 % assigned to placebo (p=0.67). The combined incidence of death or myocardial infarction occurred in 14.3 % of the patients assigned to G-CSF and 15.5 % of the patients assigned to placebo (p=0.85). In conclusion, these long-term follow-up data show that G-CSF does not improve clinical outcomes of patients with acute myocardial infarction.

  16. Combination of tadalafil and diltiazem attenuates renal ischemia reperfusion-induced acute renal failure in rats.

    PubMed

    El-Sisi, Alaa E; Sokar, Samia S; Abu-Risha, Sally E; Ibrahim, Hanaa A

    2016-12-01

    Life threatening conditions characterized by renal ischemia/reperfusion (RIR) such as kidney transplantation, partial nephrectomy, renal artery angioplasty, cardiopulmonary bypass and aortic bypass surgery, continue to be among the most frequent causes of acute renal failure. The current study investigated the possible protective effects of tadalafil alone and in combination with diltiazem in experimentally-induced renal ischemia/reperfusion injury in rats. Possible underlying mechanisms were also investigated such as oxidative stress and inflammation. Rats were divided into sham-operated and I/R-operated groups. Anesthetized rats (urethane 1.3g/kg) were subjected to bilateral ischemia for 30min by occlusion of renal pedicles, then reperfused for 6h. Rats in the vehicle I/R group showed a significant (p˂0.05) increase in kidney malondialdehyde (MDA) content; myeloperoxidase (MPO) activity; TNF-α and IL-1β contents. In addition significant (p˂0.05) increase in intercellular adhesion molecule-1(ICAM-1) content, BUN and creatinine levels, along with significant decrease in kidney superoxide dismutase (SOD) activity. In addition, marked diffuse histopathological damage and severe cytoplasmic staining of caspase-3 were detected. Pretreatment with combination of tadalafil (5mg/kg bdwt) and diltiazem (5mg/kg bdwt) resulted in reversal of the increased biochemical parameters investigated. Also, histopathological examination revealed partial return to normal cellular architecture. In conclusion, pretreatment with tadalafil and diltiazem combination protected against RIR injury.

  17. Characterization of Circulating Endothelial Cells in Acute Myocardial Infarction

    PubMed Central

    Damani, Samir; Bacconi, Andrea; Libiger, Ondrej; Chourasia, Aparajita H.; Serry, Rod; Gollapudi, Raghava; Goldberg, Ron; Rapeport, Kevin; Haaser, Sharon; Topol, Sarah; Knowlton, Sharen; Bethel, Kelly; Kuhn, Peter; Wood, Malcolm; Carragher, Bridget; Schork, Nicholas J.; Jiang, John; Rao, Chandra; Connelly, Mark; Fowler, Velia M.; Topol, Eric J.

    2013-01-01

    Acute myocardial infarction (MI), which involves the rupture of existing atheromatous plaque, remains highly unpredictable despite recent advances in the diagnosis and treatment of coronary artery disease. Accordingly, a biomarker that can predict an impending MI is desperately needed. Here, we characterize circulating endothelial cells (CECs) using the first automated and clinically feasible CEC 3-channel fluorescence microscopy assay in 50 consecutive patients with ST-elevation myocardial infarction (STEMI) and 44 consecutive healthy controls. CEC counts were significantly elevated in MI cases versus controls with median numbers of 19 and 4 cells/ml respectively (p = 1.1 × 10−10). A receiver-operating characteristic (ROC) curve analysis demonstrated an area under the ROC curve of 0.95, suggesting near dichotomization of MI cases versus controls. We observed no correlation between CECs and typical markers of myocardial necrosis (ρ=0.02, CK-MB; ρ=−0.03, troponin). Morphologic analysis of the microscopy images of CECs revealed a 2.5-fold increase (P<0.0001) in cellular area and 2-fold increase (P<0.0001) in nuclear area of MI CECs versus healthy control, age-matched CECs, as well as CECs obtained from patients with preexisting peripheral vascular disease. The distribution of CEC images containing from 2 up to 10 nuclei demonstrates that MI patients are the only group to contain more than 3 nuclei/image, indicating that multi-cellular and multi-nuclear clusters are specific for acute MI. These data indicate that CECs may serve as promising biomarkers for the prediction of atherosclerotic plaque rupture events. PMID:22440735

  18. Soy Isoflavone Protects Myocardial Ischemia/Reperfusion Injury through Increasing Endothelial Nitric Oxide Synthase and Decreasing Oxidative Stress in Ovariectomized Rats

    PubMed Central

    Tang, Yan; Li, Shuangyue; Zhang, Ping; Zhu, Jinbiao; Meng, Guoliang; Xie, Liping; Yu, Ying; Ji, Yong; Han, Yi

    2016-01-01

    There is a special role for estrogens in preventing and curing cardiovascular disease in women. Soy isoflavone (SI), a soy-derived phytoestrogen, has similar chemical structure to endogenous estrogen-estradiol. We investigate to elucidate the protective mechanism of SI on myocardial ischemia/reperfusion (MI/R) injury. Female SD rats underwent bilateral ovariectomy. One week later, rats were randomly divided into several groups, sham ovariectomy (control group), ovariectomy with MI/R, or ovariectomy with sham MI/R. Other ovariectomy rats were given different doses of SI or 17β-estradiol (E2). Four weeks later, they were exposed to 30 minutes of left coronary artery occlusion followed by 6 or 24 hours of reperfusion. SI administration significantly reduced myocardial infarct size and improved left ventricle function and restored endothelium-dependent relaxation function of thoracic aortas after MI/R in ovariectomized rats. SI also decreased serum creatine kinase and lactate dehydrogenase activity, reduced plasma malonaldehyde, and attenuated oxidative stress in the myocardium. Meanwhile, SI increased phosphatidylinositol 3 kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) signal pathway. SI failed to decrease infarct size of hearts with I/R in ovariectomized rats if PI3K was inhibited. Overall, these results indicated that SI protects myocardial ischemia/reperfusion injury in ovariectomized rats through increasing PI3K/Akt/eNOS signal pathway and decreasing oxidative stress. PMID:27057277

  19. Thallium-201 versus technetium-99m pyrophosphate myocardial imaging in detection and evaluation of patients with acute myocardial infarction

    SciTech Connect

    Pitt, B.; Thrall, J.H.

    1980-12-18

    Thallium-201 myocardial imaging is of value in the early detection and evaluation of patients with suspected acute infarction. Thallium imaging may have a special value in characterizing patients with cardiogenic shock and in detecting patients at risk for subsequent infarction or death or death or both, before hospital discharge. Approximately 95 percent of pateints with transmural or nontransmural myocardial infarction can be detected with technetium-99m pyrophosphate myocardial imaging if the imaging is performed 24 to 72 hours after the onset of symptoms. Pyrophosphate imaging may have an important role in the evaluation of patients during the early follow-up period after hospital discharge from an episode of acute infarction. The finding of a persistently positive pyrophosphate image suggests a poor prognosis and is associated with a relatively large incidence of subsequent myocardial infarction and death.

  20. [Protocol for the care of acute myocardial infarction in emergency: Código infarto (The Infarction Code)].

    PubMed

    Borrayo-Sánchez, Gabriela; Pérez-Rodríguez, Gilberto; Martínez-Montañez, Olga Georgina; Almeida-Gutiérrez, Eduardo; Ramírez-Arias, Erick; Estrada-Gallegos, Joel; Palacios-Jiménez, Norma Magdalena; Rosas-Peralta, Martín; Arizmendi-Uribe, Efraín; Arriaga-Dávila, Jesús

    2017-01-01

    Cardiovascular diseases are a major public health problem because of their they impact on more than 30% of all deaths worldwide. In our country and in the Instituto Mexicano del Seguro Social (IMSS) are also the leading cause of death and the main cause of lost of healthy life years due to disability or premature death. 50% of deaths are premature; most of them are due to acute myocardial infarct. However, the investment for cardiovascular health is poor and there are no comprehensive cares programs focused on the treatment of this diseases or the control of their risk factors. To address this problem, the first institutional care program was developed, called "A todo corazón", which aims to strengthen actions to promote healthy habits, prevention and care of cardiovascular diseases. The initial approach is to implement a protocol of care emergency services called "Código infarto", which is intended to ensure the diagnosis and treatment of patients demanding emergency care for acute myocardial infarction and receive reperfusion treatment with primary angioplasty in the first 90 minutes, or fibrinolytic therapy in the first 30 minutes after the admission to the IMSS emergency services.

  1. Clinical and angiographic correlation of high-sensitivity C-reactive protein with acute ST elevation myocardial infarction

    PubMed Central

    Tanveer, Syed; Banu, Shaheena; Jabir, Nasimudeen Rehumathbeevi; Khan, Mohd Shahnawaz; Ashraf, Ghulam Md; Manjunath, Nanjappa Cholenahally; Tabrez, Shams

    2016-01-01

    Vascular inflammation and associated ongoing inflammatory responses are considered as the critical culprits in the pathogenesis of acute atherothrombotic events such as acute coronary syndrome (ACS) and myocardial infarction (MI). ST segment elevation myocardial infarction (STEMI) is considered as one of the prominent clinical forms of ACS. Moreover, C-reactive protein (CRP) is an important acute phase prsotein, which may be estimated using high-sensitivity methods (hs-CRP), and its elevated level in body fluids reflects chronic inflammatory status. The circulating hs-CRP level has been proposed as a promising inflammatory marker of coronary artery disease (CAD). The present study investigated the correlation of hs-CRP level with clinical and angiographic features of STEMI, various other traditional risk factors, complications of myocardial infarction and angiographically significant CAD. Out of 190 patients with STEMI that were analyzed, the interval between symptom onset and reperfusion therapy (window period) varied from 0.5 to 24 h. The hs-CRP value was found to be higher in non-diabetic patients (0.61 mg/dl) compared with diabetic patients (0.87 mg/dl). Moreover, a significant correlation between hs-CRP and hs-troponin T was also recorded (P<0.001). However, there was no significant difference in the mean hs-CRP values in patients with or without mortality. It is considered that the present study will increase the understanding of atherosclerosis in general and may also have clinical applications in the targeting of therapy for this harmful disease. PMID:28105138

  2. Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondria Apoptosis Pathway

    PubMed Central

    Wu, Yang; Leng, Yan; Meng, Qingtao; Xue, Rui; Zhao, Bo; Zhan, Liying

    2017-01-01

    Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R). Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA). TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP), and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim. PMID:28191472

  3. Novel adjunctive treatments of myocardial infarction

    PubMed Central

    Schmidt, Michael Rahbek; Pryds, Kasper; Bøtker, Hans Erik

    2014-01-01

    Myocardial infarction is a major cause of death and disability worldwide and myocardial infarct size is a major determinant of prognosis. Early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome, but reperfusion may induce further myocardial damage itself. Development of adjunctive therapies to limit myocardial reperfusion injury beyond opening of the coronary artery gains increasing attention. A vast number of experimental studies have shown cardioprotective effects of ischemic and pharmacological conditioning, but despite decades of research, the translation into clinical effects has been challenging. Recently published clinical studies, however, prompt optimism as novel techniques allow for improved clinical applicability. Cyclosporine A, the GLP-1 analogue exenatide and rapid cooling by endovascular infusion of cold saline all reduce infarct size and may confer clinical benefit for patients admitted with acute myocardial infarcts. Equally promising, three follow-up studies of the effect of remote ischemic conditioning (RIC) show clinical prognostic benefit in patients undergoing coronary surgery and percutaneous coronary intervention. The discovery that RIC can be performed noninvasively using a blood pressure cuff on the upper arm to induce brief episodes of limb ischemia and reperfusion has facilitated the translation of RIC into the clinical arena. This review focus on novel advances in adjunctive therapies in relation to acute and elective coronary procedures. PMID:24976915

  4. Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway.

    PubMed

    Cui, Yuan-Chen; Pan, Chun-Shui; Yan, Li; Li, Lin; Hu, Bai-He; Chang, Xin; Liu, Yu-Ying; Fan, Jing-Yu; Sun, Kai; -Li, Quan; Han, Jing-Yan

    2017-03-22

    Cardiac ischemia and reperfusion (I/R) injury remains a challenge for clinicians. Ginsenoside Rb1 (Rb1) has been reported to have the ability to attenuate I/R injury, but its effect on energy metabolism during cardiac I/R and the underlying mechanism remain unknown. In this study, we detected the effect of Rb1 on rat myocardial blood flow, myocardial infarct size, cardiac function, velocity of venule red blood cell, myocardial structure and apoptosis, energy metabolism and change in RhoA signaling pathway during cardiac I/R injury. In addition, the binding affinity of RhoA to Rb1 was detected using surface plasmon resonance (SPR). Results showed that Rb1 treatment at 5 mg/kg/h protected all the cardiac injuries induced by I/R, including damaged myocardial structure, decrease in myocardial blood flow, impaired heart function and microcirculation, cardiomyocyte apoptosis, myocardial infarction and release of myocardial cTnI. Rb1 also inhibited the activation of RhoA signaling pathway and restored the production of ATP during cardiac I/R. Moreover, SPR assay showed that Rb1 was able to bind to RhoA in a dose-dependent manner. These results indicate that Rb1 may prevent I/R-induced cardiac injury by regulation of RhoA signaling pathway, and may serve as a potential regime to improve percutaneous coronary intervention outcome.

  5. Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway

    PubMed Central

    Cui, Yuan-Chen; Pan, Chun-Shui; Yan, Li; Li, Lin; Hu, Bai-He; Chang, Xin; Liu, Yu-Ying; Fan, Jing-Yu; Sun, Kai; -Li, Quan; Han, Jing-Yan

    2017-01-01

    Cardiac ischemia and reperfusion (I/R) injury remains a challenge for clinicians. Ginsenoside Rb1 (Rb1) has been reported to have the ability to attenuate I/R injury, but its effect on energy metabolism during cardiac I/R and the underlying mechanism remain unknown. In this study, we detected the effect of Rb1 on rat myocardial blood flow, myocardial infarct size, cardiac function, velocity of venule red blood cell, myocardial structure and apoptosis, energy metabolism and change in RhoA signaling pathway during cardiac I/R injury. In addition, the binding affinity of RhoA to Rb1 was detected using surface plasmon resonance (SPR). Results showed that Rb1 treatment at 5 mg/kg/h protected all the cardiac injuries induced by I/R, including damaged myocardial structure, decrease in myocardial blood flow, impaired heart function and microcirculation, cardiomyocyte apoptosis, myocardial infarction and release of myocardial cTnI. Rb1 also inhibited the activation of RhoA signaling pathway and restored the production of ATP during cardiac I/R. Moreover, SPR assay showed that Rb1 was able to bind to RhoA in a dose-dependent manner. These results indicate that Rb1 may prevent I/R-induced cardiac injury by regulation of RhoA signaling pathway, and may serve as a potential regime to improve percutaneous coronary intervention outcome. PMID:28327605

  6. Acute tuberculous myopericarditis mimicking acute myocardial infarction: A case report and literature review

    PubMed Central

    REN, MANYI; ZHANG, CHUNSHENG; ZHANG, XIAOJUAN; ZHONG, JINGQUAN

    2016-01-01

    A number of cases of acute myopericarditis mimicking acute myocardial infarction (AMI) have previously been reported in the literature. However, to the best of our knowledge, such a case resulting from Mycobacterium tuberculosis infection has not previously been described. The present study reports the case of a 21-year-old male patient presenting with acute chest pain, in whom focal ST-segment elevation and elevated cardiac enzymes mimicked a diagnosis of AMI. However, acute tuberculous myopericarditis was diagnosed on the basis of a variety of imaging examinations, laboratory tests, as well as the changes observed in electrocardiograms (ECGs) and in the cardiac enzyme levels. The case highlights the importance of a detailed collection of medical history, comprehensive explanations of serial ECGs, thoracic computed tomography, echocardiogram and coronary angiography in the diagnosis and differentiation of acute tuberculous myopericarditis mimicking AMI. PMID:27284323

  7. Peroxisome proliferator-activated receptor γ (PPARγ) mediates the protective effect of quercetin against myocardial ischemia-reperfusion injury via suppressing the NF-κB pathway

    PubMed Central

    Liu, Xinyu; Yu, Zhangjie; Huang, Xian; Gao, Yi; Wang, Xiuzhi; Gu, Jianmin; Xue, Song

    2016-01-01

    Quercetin plays an important role in myocardial ischemia and reperfusion injury (IRI). However, the underlying mechanism for the protective effect of quercetin is largely unclear. In this study, we explored the protected effects of quercetin against myocardial IRI and its molecular mechanisms. Quercetin, GW9962 (PPARγ antagonist) or PPARγ-siRNA was administered alone or in combination prior to myocardial IRI in mice or to hypoxia and reoxygenation (H/R) treatment in H9C2 cells. Infarct size was evaluated by TTC staining after reperfusion. Myocardial injury was assessed by the serum levels of AST, CK-MB, cardiac troponin T (cTnT) and LDH. Cardiac function was measured by echocardiography. Oxidative stress injury was evaluated by analyses of inducible nitric oxide synthase (iNOS), MDA, SOD and glutathione peroxidase (GSH-PX) levels and by reactive oxygen species (ROS) detection. Myocardium apoptosis was evaluated by TUNEL staining, cleaved caspase-3 and Annexin V/PI detection. Moreover, activation of the NF-κB pathway was reflected by phosphorylation of IκB (p-IκB) and nuclear translocation of NF-κB p65. We reported that pretreatment of quercetin significantly improved cardiac function, diminished myocardial injury and reduced the infarct size. Myocardium oxidative damage and apoptosis were remarkably improved by quercetin treatment in vivo and in vitro. Quercetin also suppressed the activation of the NF-κB pathway induced by myocardial IRI. GW9662 or PPARγ knockdown partially attenuated these cardioprotective effects of quercetin during myocardial IRI. In conclusion, our findings suggest that quercetin ameliorated IRI-induced heart damage via PPARγ activation and the underlying mechanism might involve the inhibition of NF-κB pathway by PPARγ activation. PMID:28077993

  8. Acute ST Elevation Myocardial Infarction in Patients With Immune Thrombocytopenia Purpura: A Case Report

    PubMed Central

    Dhillon, Sandeep K; Lee, Edwin; Fox, John; Rachko, Maurice

    2011-01-01

    Acute myocardial infarction (AMI) in patients with immune thrombocytopenic purpura (ITP) is rare. We describe a case of AMI in patient with ITP. An 81-year-old woman presented with acute inferoposterior MI with low platelet count on admission (34,000/µl). Coronary angiography revealed significant mid right coronary artery (RCA) stenosis with thrombus, subsequently underwent successful percutaneous coronary intervention (PCI). In some patients with immune thrombocytopenia purpura and acute myocardial infarction, percutaneous coronary intervention is a therapeutic option.

  9. Diurnal variation in myocardial ischemia/reperfusion tolerance; mediation by the circadian clock within the cardiomyocyte

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms in cardiovascular physiology (e.g. blood pressure and heart rate) and pathophysiology (e.g. myocardial infarction (MI)) exist. Humans exhibit a marked increase in MI frequency during the early hours of the morning. However, MIs occurring during the evening are more likely to result...

  10. [Treatment of acute ST Elevation myocardial infarction in a regional network ("Drip & Ship Network Rostock")].

    PubMed

    Schneider, Henrik; Ince, Hüseyin; Rehders, Tim; Körber, Thomas; Weber, Frank; Kische, Stephan; Chatterjee, Tuchaar; Nienaber, Christoph A

    2007-12-01

    Management of acute ST elevation myocardial infarction (STEMI) demands rapid and complete reperfusion of the infarct-related artery (IRA). With postinfarction prognosis depending on time delay from onset of symptoms to complete reperfusion (TIMI 3 flow) of the IRA, primary percutaneous coronary intervention (PPCI) performed by an experienced team has been shown to be superior to thrombolytic therapy with lower mortality, less frequent occurrence of nonfatal reinfarction and stroke, and thus represents the preferred treatment strategy according to the national and international guidelines. For regional implementation of PPCI, particularly in rural areas, information and transfer logistics within networks of care and direct transport of an infarction patient to a PCI hospital rather than to the closest hospital are a challenge. With successful implementation of network logistics and standardized therapeutic pathways, current guidelines and requested timelines versus thrombolysis could be met. The implemented logistics comprised 24 h/7 days stand-by services of an experienced PCI team, direct telephone hotline contact between rescue service/emergency physician and interventional cardiologist on call, and direct open access to a catheterization laboratory at any time. Within the Drip&Ship network Rostock, to date (July 2007) 1,022 consecutive patients with PCI for STEMI were documented and analyzed over 5 years; of these, 490 patients were transferred from a community hospital to the PCI center and 532 patients were admitted directly to the interventional center. In 95.1% of all transferred and in 94.8% of all directly admitted patients, PCI was successfully accomplished upon arrival. A normalized flow to the IRA after PCI was documented in 96% of both groups, no patient was subjected to thrombolytic therapy. At 12-month follow-up, there were no differences between both groups with respect to infarct size and mortality. Moreover, there was no evidence of differences in

  11. Protective effect of butin against ischemia/reperfusion-induced myocardial injury in diabetic mice: involvement of the AMPK/GSK-3β/Nrf2 signaling pathway

    PubMed Central

    Duan, Jialin; Guan, Yue; Mu, Fei; Guo, Chao; Zhang, Enhu; Yin, Ying; Wei, Guo; Zhu, Yanrong; Cui, Jia; Cao, Jinyi; Weng, Yan; Wang, Yanhua; Xi, Miaomiao; Wen, Aidong

    2017-01-01

    Hyperglycemia-induced reactive oxygen species (ROS) generation contributes to development of diabetic cardiomyopathy (DCM). This study was designed to determine the effect of an antioxidant butin (BUT) on ischemia/reperfusion-induced myocardial injury in diabetic mice. Myocardial ischemia/reperfusion (MI/R) was induced in C57/BL6J diabetes mice. Infarct size and cardiac function were detected. For in vitro study, H9c2 cells were used. To clarify the mechanisms, proteases inhibitors or siRNA were used. Proteins levels were investigated by Western blotting. In diabetes MI/R model, BUT significantly alleviated myocardial infarction and improved heart function, together with prevented diabetes-induced cardiac oxidative damage. The expression of Nrf2, AMPK, AKT and GSK-3β were significantly increased by BUT. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the BUT’s prevention of I/R-induced myocardial injury. Inhibition of AMPK and AKT signaling by relative inhibitor or specific siRNA decreased the level of BUT-induced Nrf2 expression, and diminished the protective effects of BUT. The interplay relationship between GSK-3β and Nrf2 was also verified with relative overexpression and inhibitors. Our findings indicated that BUT protected against I/R-induced ROS-mediated apoptosis by upregulating the AMPK/Akt/GSK-3β pathway, which further activated Nrf2-regulated antioxidant enzymes in diabetic cardiomyocytes exposed to I/R. PMID:28128361

  12. QT dispersion and early arrhythmic risk during acute myocardial infarction.

    PubMed

    Paventi, S; Bevilacqua, U; Parafati, M A; Di Luzio, E; Rossi, F; Pelliccioni, P R

    1999-03-01

    It has been suggested that QT dispersion (maximal minus minimal QT interval calculated on a standard 12-lead electrocardiogram) could reflect regional variations of ventricular repolarization and could provide a substrate for reentry ventricular arrhythmias. The present study evaluates QT dispersion in patients with acute myocardial infarction, assessing its relation with early severe ventricular arrhythmias and some clinical features. Three hundred three patients with acute myocardial infarction and a control group of 297 healthy subjects were studied. QT and QTc dispersion were determined on the electrocardiogram taken after 12 hours and on days 3 and 10 after symptoms onset and on the electrocardiogram taken in the control group. The average values of QT and QTc dispersions (ms) were as follows: 70.5 +/- 42.5-87 +/- 45.6 (12th hour), 66.7 +/- 37.6-76.8 +/- 43.6 (day 3), 68.8 +/- 42.7-76.8 +/- 42.8 (day 10), versus 43 +/- 13.2-53.9 +/- 16.2 (control group). There were statistically significant differences between QT and QTc dispersion recorded in normal subjects and in each of the three electrocardiograms taken in patients with infarction. A greater QT dispersion was recorded in patients with anterior infarction (78.9 +/- 38.5 vs 64.9 +/- 42.8 in inferior/lateral infarction). In the first 3 days QT dispersion was not different in patients treated and untreated with thrombolysis, whereas on day 10 it was greater in untreated patients (74.9 +/- 45.3 vs 60.5 +/- 37.2). Creatine kinase peak level did not influence QT dispersion. In the first 72 hours of infarction, 37 patients developed ventricular fibrillation or sustained ventricular tachycardia. Higher early values of QT and QTc dispersion were found in patients who developed severe ventricular arrhythmias (107.8 +/- 62 and 124.8 +/- 67.5 ms) than in patients without serious arrhythmias (62.9 +/- 32.2 and 80.1 +/- 37.9 ms). These data suggest that: (1) QT dispersion increased during acute myocardial infarction. (2

  13. Pharmacologic Reperfusion Therapy with Indigenous Tenecteplase in 15,222 patients with ST Elevation Myocardial Infarction – The Indian Registry

    PubMed Central

    Iyengar, S.S.; Nair, T.; Hiremath, J.S.; Jadhav, U.; Katyal, V.K.; Kumbla, D.; Sathyamurthy, I.; Jain, R.K.; Srinivasan, M.

    2013-01-01

    Objective To study the efficacy and safety of single intravenous bolus administration of indigenously developed tenecteplase (TNK-tPA) in the management of patients with ST-elevation myocardial infarction (STEMI) in clinical practice. Methods Observational, prescription-event monitoring study. Results Data of 15,222 patients who had STEMI and received weight adjusted TNK injection was analyzed. Overall 95.43% patients had clinically successful thrombolysis (CST). In the different subgroups, hypertensives, diabetics, smokers and hyperlipidemic patients had CST rates comparable to the general patient data. CST rates were significantly lower in the elderly patients (>70 years; 92.11%; p < 0.0001), in patients with history of Ischemic Heart Disease (IHD, 93.86%; p = 0.0004) and in patients receiving delayed treatment (>6 h after onset of chest pain; 85.38%; p < 0.0001). CST was significantly higher in patients who received an early thrombolysis (<3 h after onset of chest pain; 96.54%; p = 0.006). Overall mortality was 1.69%, while it was significantly higher in the elderly (4.42%), patients with history of IHD (2.67%), females (2.93%) and in those who received delayed treatment (4.98%). The overall incidences of intracranial hemorrhage (ICH), bleeding excluding ICH, stroke and ventricular tachyarrhythmia were 0.39%, 2.01%, 0.16% and 2.35% respectively. Age >70 years, diabetes, hyperlipidemia and history of IHD were associated with a higher incidence of heart failure, myocardial re-infarction or ventricular tachyarrhythmias. However, incidence of ICH and bleeding other than ICH was comparable amongst all patient subgroups. Conclusion This study confirms the safety and efficacy of indigenous tenecteplase in Indian patients with STEMI, including high risk subgroups. It also highlights the fact that delayed treatment denotes denial of benefits of pharmacologic reperfusion therapy. PMID:23993004

  14. Sulodexide attenuates myocardial ischemia/reperfusion injury and the deposition of C-reactive protein in areas of infarction without affecting hemostasis.

    PubMed

    Lauver, D Adam; Booth, Erin A; White, Andrew J; Poradosu, Enrique; Lucchesi, Benedict R

    2005-02-01

    Several glycosaminoglycans (GAGs) have been demonstrated to protect the ischemic heart against reperfusion injury, in part, by modulating activation of the complement cascade. The present study assessed the cardioprotective effects of sulodexide (KRX-101), a mixture of GAGs composed of 80% low-molecular mass heparin and 20% dermatan sulfate. KRX-101 differs from other GAGs (e.g., heparin) in that it has limited anticoagulant efficacy and can be administered orally. The experimental protocol was designed to determine whether KRX-101 could protect the ischemic myocardium. Anesthetized New Zealand white rabbits underwent 30 min of coronary artery occlusion. Intravenous doses of KRX-101 (0.5 mg/kg, n = 10) or drug diluent (n = 10) were administered at the end of regional ischemia and at each hour of reperfusion. Infarct size, as a percentage of the area at risk, was calculated for both groups. Myocardial infarct size was 31.3 +/- 4.1% in the vehicle- and 17.3 +/- 3.2% in the KRX-101-treated animals (p < 0.05 versus vehicle). Activated partial thromboplastin times determined at baseline (preischemia) and at each hour of reperfusion (n = 4) were not significantly different between vehicle- and KRX-101-treated groups (p = N.S.). Myocardial injury was further assessed by measuring serum levels of cardiac-specific troponin I. KRX-101 administration significantly reduced (p < 0.05) the serum concentration of troponin I during reperfusion. The results suggest that KRX-101 may be an effective adjunctive agent in myocardial revascularization procedures, without the risk of increased bleeding.

  15. Sequential thallium-201 myocardial scintigraphy after acute infarction in man

    SciTech Connect

    Fletcher, J.W.; Mueller, H.S.; Rao, P.S.

    1980-07-01

    Three sequential Tl-201 myocardial perfusion studies were performed in 21 patients (18 men, 3 women) with first acute transmural myocardia infarction. The Tl-201 image defect size was determined with a semiquantitative visual scoring method and temporal changes in image defect size were compared to CK-MB infarct size and enzymatic evidence of progressive myocardial necrosis and infarct extension. Progressive decreases in Tl-201 image defect size were observed and the visual score in all 21 patients decreased significantly from 6.5 +- 3.7 (mean +- SD) on day 1 to 4.9 +- 3.5 on day 12. Eleven patients without evidence of infarct extension had significantly lower infarct size, a significant decrease in visual score by the 12th day and had significantly smaller Tl-201 defects at all three study times compared to 10 patients with infarct extension. Seven of 10 (70%) with extension had an initial visual score greater than or equal to 7 compared to only 2/11 (18%) without extension. The temporal behavior of Tl-201 image defects is related to the size of the infarction and presence or absence of extension. Sequential studies comparing early initial and subsequent defect size may assist in evaluating the behavior of ischemic and infarcted myocardium in the postinfarction period.

  16. MOEMS-based cardiac enzymes detector for acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Amritsar, Jeetender; Stiharu, Ion G.; Packirisamy, Muthukumaran; Balagopal, Ganesharam; Li, Xing

    2004-10-01

    Biomedical applications of MOEMS are limited only by the mankind imagination. Precision measurements on minute amounts of biological material could be performed by optical means with a remarkable accuracy. Although available in medical laboratories for general purposes, such analyzers are making their way directly to the users in the form of dedicated equipment. Such an example is a test kit to detect the existence of cardiac enzymes in the blood stream. Apart from the direct users, the medical personnel will make use of such tools given the practicality of the kit. In a large proportion of patients admitted to the hospital suspected of Acute Myocardial Infarction (AMI), the symptoms and electrocardiographic changes are inconclusive. This necessitates the use of biochemical markers of myocardial damage for correct exclusion or conformation of AMI. In this study the concept of MOEMS is applied for the detection of enzyme reaction, in which glass spectrums are scanned optically when enzyme molecules adsorb on their surface. This paper presents the optical behavior of glass spectrums under Horseradish Peroxide (HRP) enzyme reaction. The reported experimental results provide valuable information that will be useful in the development of biosensors for enzymatic detection. This paper also reports the dynamic behavior of different glass spectrums.

  17. L-carnitine for the treatment of acute myocardial infarction.

    PubMed

    Dinicolantonio, James J; Niazi, Asfandyar K; McCarty, Mark F; Lavie, Carl J; Liberopoulos, Evangelos; O'Keefe, James H

    2014-01-01

    Although the therapeutic strategies available for treating acute myocardial infarction (AMI) have evolved dramatically in recent decades, coronary artery disease remains the leading cause of death in our society, and the rates of recurrent myocardial infarction and mortality are still unacceptably high. Therefore, exploration of alternative therapeutic strategies for AMI is of utmost importance. One such strategy is to target metabolic pathways via L-carnitine supplementation. L-carnitine is a physiologically essential metabolic cofactor that has been shown to provide a plethora of benefits when administered after AMI. L-carnitine has been shown to lessen infarct size, to reduce ventricular arrhythmias, left ventricular dilation, and heart failure incidence, as well as improve survival. These benefits may, in part, be related to its ability to boost glucose oxidation in ischemic tissues, while moderating increases in fatty acyl-coenzyme A levels that can impair mitochondrial efficiency and promote oxidative stress and inflammation. This article summarizes the evidence pertinent to the therapeutic use of L-carnitine for AMI.

  18. The cardioprotective actions of hydrogen sulfide in acute myocardial infarction and heart failure.

    PubMed

    Polhemus, David J; Calvert, John W; Butler, Javed; Lefer, David J

    2014-01-01

    It has now become universally accepted that hydrogen sulfide (H2S), previously considered only as a lethal toxin, has robust cytoprotective actions in multiple organ systems. The diverse signaling profile of H2S impacts multiple pathways to exert cytoprotective actions in a number of pathological states. This paper will review the recently described cardioprotective actions of hydrogen sulfide in both myocardial ischemia/reperfusion injury and congestive heart failure.

  19. Acute myocardial infarction as a finding of acute promyelocytic leukemia-related coagulation disorder.

    PubMed

    Özkurt, Zübeyde N; Aypar, Eda; Sarifakiogullari, Serpil; Taçoy, Gülten; Özdag, Murat; Kahraman, Seda; Çengel, Atiye

    2015-12-01

    Acute promyelocytic leukemia (APL) has one of the most favorable prognoses among other leukemia subtypes. However, the major cause of mortality in APL is disseminated intravascular coagulation at the presentation. We present a case of acute myocardial infarction (MI) at the time of APL diagnosis before treatment. The patient suffered from chest pain, sweating and giddiness. He was hypoxic, hypotensive and bradycardic. ECG showed inferior MI. Unfractioned heparin infusion (850 U/h) was started and 5 min after the previous ECG showed total ST resolution. We suggest that in this case, MI was not related to atherosclerotic plaque rupture but related to DIC manifestation.

  20. Deciding to Seek Emergency Care for Acute Myocardial Infarction.

    PubMed

    Noureddine, Samar; Dumit, Nuhad Y; Saab, Mohammad

    2015-10-01

    The purpose of this qualitative descriptive study was to explore how patients who experience acute myocardial infarction (AMI) decide to seek emergency care. Fifty patients with AMI were interviewed at two hospitals in Lebanon. The perspective of 22 witnesses of the attack was also sought about the cardiac event. The themes that transpired from the data were as follows: making sense of the symptoms, waiting to see what happens, deciding to come to the hospital, and the family influenced the decision to seek care. The witnesses of the cardiac event, mostly family members, supported the decision to seek emergency care. Deciding to seek emergency care for AMI is complex. Nurses must solicit their patients' perception of the cardiac event to provide them with tailored education and counseling about heart attack symptoms and how to respond to them in case they recur. Family members must be included in the education process.

  1. Percutaneous coronary intervention for acute myocardial infarction with mitral regurgitation

    PubMed Central

    Tu, Yan; Zeng, Qing-Chun; Huang, Ying; Li, Jian-Yong

    2016-01-01

    Ischemic mitral regurgitation (IMR) is a common complication of acute myocardial infarction (AMI). Current evidences suggest that revascularization of the culprit vessels with percutaneous coronary artery intervention (PCI) or coronary artery bypass grafting can be beneficial for relieving IMR. A 2.5-year follow-up data of a 61-year-old male patient with ST-segment elevation AMI complicated with IMR showed that mitral regurgitation area increased five days after PCI, and decreased to lower steady level three months after PCI. This finding suggest that three months after PCI might be a suitable time point for evaluating the possibility of IMR recovery and the necessity of surgical intervention of the mitral valve for AMI patient. PMID:27582769

  2. Raman spectroscopy of human saliva for acute myocardial infarction detection

    NASA Astrophysics Data System (ADS)

    Chen, Maowen; Chen, Yuanxiang; Wu, Shanshan; Huang, Wei; Lin, Jinyong; Weng, Guo-Xing; Chen, Rong

    2014-09-01

    Raman spectroscopy is a rapidly non-invasive technique with great potential for biomedical research. The aim of this study was to evaluate the feasibility of using Raman spectroscopy of human saliva for acute myocardial infarction (AMI) detection. Raman spectroscopy measurements were performed on two groups of saliva samples: one group from patients (n=30) with confirmed AMI and the other group from healthy controls (n=31). The diagnostic performance for differentiating AMI saliva from normal saliva was evaluated by multivariate statistical analysis. The combination of principal component analysis (PCA) and linear discriminate analysis (LDA) of the measured Raman spectra separated the spectral features of the two groups into two distinct clusters with little overlaps, rendering the sensitivity of 80.0% and specificity of 80.6%. The results from this exploratory study demonstrated that Raman spectroscopy of human saliva can serve as a potentially clinical tool for rapid AMI detection and screening.

  3. A case of acute myocardial infarction during 5-fluorouracil infusion.

    PubMed

    Canale, Maria Laura; Camerini, Andrea; Stroppa, Stefano; Porta, Romana Prosperi; Caravelli, Paolo; Mariani, Mario; Balbarini, Alberto; Ricci, Sergio

    2006-11-01

    Cardiac toxicity is an uncommon side-effect of 5-fluorouracil (5-FU) treatment, consisting mainly of chest pain episodes with or without electrocardiographic changes and dysrhythmias. Here, we describe the case of a 56-year-old male patient with a diagnosis of advanced colorectal cancer who developed an acute myocardial infarction during 5-FU infusion. The patient was not affected by prior heart disease and did not show any classic risk factors for coronary heart disease. Coronary angiography examination revealed no evidence of coronary stenosis, supporting the hypothesis of a coronary artery spasm related to 5-FU infusion. Given the great number of cancer patients receiving 5-FU containing chemotherapeutic regimens, this rare but severe cardiac side-effect may be observed in both cardiologic and oncologic clinical practice. We suggest a tight clinical monitoring of all patients receiving 5-FU infusions, even in those without a prior history of heart disease.

  4. [Effect of mexicor on oxidative stress in acute myocardial infarction].

    PubMed

    Golikov, A P; Davydov, B V; Rudnev, D V; Klychnikova, E V; Bykova, N S; Riabinin, V A; Polumiskov, V Iu; Nikolaeva, N Iu; Golikov, P P

    2005-01-01

    Mexicor (5% solution and capsules) was used in 40 of 80 conventionally treated patients with acute myocardial infarction. The drug was given intravenously for 5 days, than intramuscularly (6-9 mg/kg) for 9 days and orally (0.1 mg t.i.d.) thereafter until discharge. Severity of oxidative stress was evaluated by K coefficient. Calculation of this coefficient required data on degree of oxidation of lipids in blood serum, serum levels of diene conjugates, malonic dialdehyde, alpha-tocopherol and ceruloplasmin. These parameters as well as activity of superoxide dismutase, glutathione peroxidase and catalase in erythrocytes were measured at admission, on days 2, 3, 7, 14 and at discharge. Mexicor treated compared with untreated (n=40) patients were characterized by diminished severity of oxidative stress at the account of lower levels of lipid peroxidation products and augmented compensatory potential of the endogenous antioxidant system.

  5. Early Loss of Immediate Reperfusion while Stent Retriever in Place Predicts Successful Final Reperfusion in Acute Ischemic Stroke Patients

    PubMed Central

    Okawa, Masakazu; Tateshima, Satoshi; Liebeskind, David; Rao, Neal; Jahan, Reza; Gonzalez, Nestor; Szeder, Viktor; Ali, Latisha; Kim, Doojin; Saver, Jeffrey; Duckwiler, Gary

    2016-01-01

    BACKGROUND and PURPOSE Degree of stent retriever engagement with target thrombi may be reflected by 1) immediate reperfusion (IR) upon first deployment, indicating displacement of clot toward the vessel wall, and 2) early loss of immediate reperfusion (ELOIR), indicating penetration of retriever struts through the thrombus. The relation of these early findings to final reperfusion and clinical outcomes has not been well delineated. METHODS We investigated IR and ELOIR in patients undergoing stent retriever mechanical thrombectomy at an academic medical center between March 2012 and June 2014. RESULTS Among 56 patients, IR itself was not associated with final successful reperfusion, which occurred in 66.7% of IR patients and 71.4% of non-IR patients (p=0.999). However, ELOIR was associated a higher rate of final successful reperfusion (92% vs 44%, p = 0.046). Patients with ELOIR had a higher nominal rate of final favorable outcome (42% vs 22%, p=0.64). CONCLUSION ELOIR during the embedding period after deployment of stent retrievers is associated with SFR, likely due to greater thrombus engagement with the stent retriever. ELOIR may be a useful finding to guide duration of embedding time in clinical practice and design of novel stent retrievers. PMID:26451013

  6. Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury

    PubMed Central

    Hao, Jia; Ahn, Hee-Yul

    2012-01-01

    Akt/protein kinase B is a well-known cell survival factor and activated by many stimuli including mechanical stretching. Therefore, we evaluated the cardioprotective effect of a brief mechanical stretching of rat hearts and determined whether activation of Akt through phosphatidylinositol 3-kinase (PI3K) is involved in stretch-induced cardioprotection (SIC). Stretch preconditioning reduced infarct size and improved post-ischemic cardiac function compared to the control group. Phosphorylation of Akt and its downstream substrate, GSK-3β, was increased by mechanical stretching and completely blocked by wortmannin, a PI3K inhibitor. Treatment with lithium or SB216763 (GSK-3β inhibitors) before ischemia induction mimicked the protective effects of SIC on rat heart. Gadolinium (Gd3+), a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of Akt and GSK-3β. Furthermore, SIC was abrogated by wortmannin and Gd3+. In vivo stretching induced by an aorto-caval shunt increased Akt phosphorylation and reduced myocardial infarction; these effects were diminished by wortmannin and Gd3+ pretreatment. Our results showed that mechanical stretching can provide cardioprotection against ischemia-reperfusion injury. Additionally, the activation of Akt, which might be regulated by SACs and the PI3K pathway, plays an important role in SIC. PMID:23000580

  7. Nitrative Thioredoxin Inactivation as a Cause of Enhanced Myocardial Ischemia/Reperfusion Injury in the Aging Heart

    PubMed Central

    Zhang, Hangxiang; Tao, Ling; Jiao, Xiangying; Gao, Erhe; Lopez, Bernard L.; Christopher, Theodore A.; Koch, Walter; Ma, Xin L.

    2007-01-01

    Objective Several recent studies have demonstrated that thioredoxin (Trx) is an important anti-apoptotic/cytoprotective molecule. The present study was designed to determine whether Trx activity is altered in the aging heart in a way that may contribute to increased susceptibility to myocardial ischemia/reperfusion (MI/R). Methods and Results Compared to young animals, MI/R-induced cardiomyocyte apoptosis and infarct size were increased in aging animals (P<0.01). Trx activity was decreased in the aging heart before MI/R, and this difference was further amplified after MI/R. Trx expression was moderately increased and Trx nitration, a post-translational modification that inhibits Trx activity, was increased in the aging heart. Moreover, Trx-ASK1 complex formation was reduced and activity of p38 MAPK was increased. Treatment with FP15 (a peroxynitrite decomposition catalyst) reduced Trx nitration, increased Trx activity, restored Trx-ASK1 interaction, reduced P38 MAPK activity, attenuated caspase 3 activation and reduced infarct size in aging animals (p<0.01). Conclusions Our results demonstrated that Trx activity is decreased in the aging heart by post-translational nitrative modification. Interventions that restore Trx activity in the aging heart may be novel therapies to attenuate MI/R injury in aging patients. PMID:17561092

  8. Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90.

    PubMed

    Wang, Min; Tian, Yu; Du, Yu-Yang; Sun, Gui-Bo; Xu, Xu-Dong; Jiang, Hai; Xu, Hui-Bo; Meng, Xiang-Bao; Zhang, Jing-Yi; Ding, Shi-Lan; Zhang, Miao-di; Yang, Ming-Hua; Sun, Xiao-Bo

    2017-02-22

    The present study was designed to investigate whether Araloside C, one of the major triterpenoid compounds isolated from Aralia elata known to be cardioprotective, can improve heart function following ischaemia/reperfusion (I/R) injury and elucidate its underlying mechanisms. We observed that Araloside C concentration-dependently improved cardiac function and depressed oxidative stress induced by I/R. Similar protection was confirmed in isolated cardiomyocytes characterized by maintaining Ca(2+) transients and cell shortening against I/R. Moreover, the potential targets of Araloside C were predicted using the DDI-CPI server and Discovery Studio software. Molecular docking analysis revealed that Araloside C could be stably docked into the ATP/ADP-binding domain of the heat shock protein 90 (Hsp90) protein via the formation of hydrogen bonds. The binding affinity of Hsp90 to Araloside C was detected using nanopore optical interferometry and yielded KD values of 29 μM. Araloside C also up-regulated the expression levels of Hsp90 and improved cell viability in hypoxia/reoxygenation-treated H9c2 cardiomyocytes, whereas the addition of 17-AAG, a pharmacologic inhibitor of Hsp90, attenuated Araloside C-induced cardioprotective effect. These findings reveal that Araloside C can efficiently attenuate myocardial I/R injury by reducing I/R-induced oxidative stress and [Ca(2+) ]i overload, which was possibly related to its binding to the Hsp90 protein.

  9. Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury.

    PubMed

    Kim, Chan-Hyung; Hao, Jia; Ahn, Hee-Yul; Kim, Si Wook

    2012-09-01

    Akt/protein kinase B is a well-known cell survival factor and activated by many stimuli including mechanical stretching. Therefore, we evaluated the cardioprotective effect of a brief mechanical stretching of rat hearts and determined whether activation of Akt through phosphatidylinositol 3-kinase(PI3K) is involved in stretch-induced cardioprotection (SIC). Stretch preconditioning reduced infarct size and improved postischemic cardiac function compared to the control group. Phosphorylation of Akt and its downstream substrate, GSK-3β, was increased by mechanical stretching and completely blocked by wortmannin, a PI3K inhibitor. Treatment with lithium or SB216763 (GSK-3β inhibitors) before ischemia induction mimicked the protective effects of SIC on rat heart. Gadolinium (Gd3(+)), a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of Akt and GSK-3β. Furthermore, SIC was abrogated by wortmannin and Gd3(+). In vivo stretching induced by an aorto-caval shunt increased Akt phosphorylation and reduced myocardial infarction; these effects were diminished by wortmannin and Gd3(+) pretreatment. Our results showed that mechanical stretching can provide cardioprotection against ischemia-reperfusion injury. Additionally, the activation of Akt, which might be regulated by SACs and the PI3K pathway, plays an important role in SIC.

  10. Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes

    PubMed Central

    Zhao, Dajun

    2017-01-01

    Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress. mTOR signaling presents both cardioprotective and cardiotoxic effects on the diabetic heart, which interplays with oxidative stress directly or indirectly. Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets. In this review, we will focus on the role of oxidative stress and mTOR signaling in the pathophysiology of MI/R injury in diabetes and discuss potential mechanisms and their interactions in an effort to provide some evidence for cardiometabolic targeted therapies for ischemic heart disease (IHD). PMID:28298952

  11. Acute nonrheumatic streptococcal myocarditis resembling ST-elevation acute myocardial infarction in a young patient

    PubMed Central

    Jurado, Margarita; Porres-Aguilar, Mateo; Olivas-Chacon, Cristina; Porres-Muñoz, Mateo; Mukherjee, Debabrata; Taveras, Juan

    2015-01-01

    Acute myocarditis can be induced by various concomitant disease processes including infections. Most of these cases are viral in origin; however, bacterial infections are also implicated to a lesser degree. Group A streptococcus is a frequent culprit in bacterial-induced myocarditis. Its diagnosis is suspected by the presence of signs and symptoms of rheumatic fever as established by the Jones criteria. The development and refinement of current diagnostic tools has improved our ability to identify specific pathogens. It has been found that group A streptococcus may be responsible for more cases of infection-induced acute myocarditis than previously thought, and often without the clinical features of rheumatic fever. We present the case of a 43-year-old man hospitalized with chest pain that was initially diagnosed as an acute ST-elevation myocardial infarction. Further evaluation confirmed that his chief complaint was due to acute nonrheumatic streptococcal myocarditis. PMID:25829649

  12. Acute nonrheumatic streptococcal myocarditis resembling ST-elevation acute myocardial infarction in a young patient.

    PubMed

    Aguirre, Jose L; Jurado, Margarita; Porres-Aguilar, Mateo; Olivas-Chacon, Cristina; Porres-Muñoz, Mateo; Mukherjee, Debabrata; Taveras, Juan

    2015-04-01

    Acute myocarditis can be induced by various concomitant disease processes including infections. Most of these cases are viral in origin; however, bacterial infections are also implicated to a lesser degree. Group A streptococcus is a frequent culprit in bacterial-induced myocarditis. Its diagnosis is suspected by the presence of signs and symptoms of rheumatic fever as established by the Jones criteria. The development and refinement of current diagnostic tools has improved our ability to identify specific pathogens. It has been found that group A streptococcus may be responsible for more cases of infection-induced acute myocarditis than previously thought, and often without the clinical features of rheumatic fever. We present the case of a 43-year-old man hospitalized with chest pain that was initially diagnosed as an acute ST-elevation myocardial infarction. Further evaluation confirmed that his chief complaint was due to acute nonrheumatic streptococcal myocarditis.

  13. Heart remodeling and ischemia-reperfusion arrhythmias linked to myocardial vitamin d receptors deficiency in obstructive nephropathy are reversed by paricalcitol.

    PubMed

    Diez, Emiliano Raúl; Altamirano, Liliana Berta; García, Isabel Mercedes; Mazzei, Luciana; Prado, Natalia Jorgelina; Fornes, Miguel Walter; Carrión, Fernando Darío Cuello; Zumino, Amira Zulma Ponce; Ferder, León; Manucha, Walter

    2015-03-01

    Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors (VDRs) are among the probable links between the 2 disorders. The vitamin D receptor activator paricalcitol protects against some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D receptor modification and its impact on the response to ischemia-reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and Sham-operated rats were treated with either paricalcitol (30 ng/kg/d intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in VDRs and an increase in angiotensin II type 1 receptor expression (messenger RNA and protein), suffered fibrosis (determined by Masson trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction in myocardial vitamin D receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D receptor levels and prolonging action potentials.

  14. Safety and tolerance data from the Belgian multicentre study of anisoylated plasminogen streptokinase activator complex versus heparin in acute myocardial infarction.

    PubMed

    Bossaert, L L

    1987-01-01

    In the European Multicentre Study (EMS), the safety and efficacy of a single 30U intravenous injection of anisoylated plasminogen streptokinase activator complex (APSAC) was studied in patients with acute myocardial infarction. The present study discusses the Belgian data on safety and tolerance from the EMS study. 87 patients were randomised to treatment with APSAC or heparin. The reperfusion rate was 60.5% (APSAC) versus 20.5% (heparin control), and reocclusion occurred in 21% of the reperfused APSAC patients. Drug-related adverse events consisted of bleeding problems (7 events in patients on APSAC and 1 event in a patient on heparin and moderate allergic reactions (12 events in 9 patients on APSAC and 1 event in a heparin patient). There was 1 drug-related death in the APSAC group (hypovolaemic shock due to central vein puncture during lytic state) which could have been avoided. It is concluded that thrombolytic treatment of acute myocardial infarction with APSAC is effective and safe, as long as the standard precautions for thrombolytic treatment are respected. Bleeding and allergic-type events are infrequent, usually well tolerated and easily treated.

  15. The role of technetium-99m stannous pyrophosphate in myocardial imaging to recognize, localize and identify extension of acute myocardial infarction in patients

    NASA Technical Reports Server (NTRS)

    Willerson, J. T.; Parkey, R. W.; Bonte, F. J.; Stokely, E. M.; Buja, E. M.

    1975-01-01

    The ability of technetium-99m stannous pyrophosphate myocardial scintigrams to aid diagnostically in recognizing, localizing, and identifying extension of acute myocardial infarction in patients was evaluated. The present study is an extension of previous animal and patient evaluations that were recently performed utilizing this myocardial imaging agent.

  16. The non-anticoagulant heparin-like K5 polysaccharide derivative K5-N,OSepi attenuates myocardial ischaemia/reperfusion injury

    PubMed Central

    Collino, Massimo; Pini, Alessandro; Mastroianni, Rosanna; Benetti, Elisa; Lanzi, Cecilia; Bani, Daniele; Chini, Jacopo; Manoni, Marco; Fantozzi, Roberto; Masini, Emanuela

    2012-01-01

    Heparin and low molecular weight heparins have been demonstrated to reduce myocardial ischaemia/reperfusion (I/R) injury, although their use is hampered by the risk of haemorrhagic and thrombotic complications. Chemical and enzymatic modifications of K5 polysaccharide have shown the possibility of producing heparin-like compounds with low anticoagulant activity and strong anti-inflammatory effects. Using a rat model of regional myocardial I/R, we investigated the effects of an epimerized N-,O-sulphated K5 polysaccharide derivative, K5-N,OSepi, on infarct size and histological signs of myocardial injury caused by 30 min. ligature of the left anterior descending coronary artery followed by 1 or 24 h reperfusion. K5-N,OSepi (0.1–1 mg/kg given i.v. 15 min. before reperfusion) significantly reduced the extent of myocardial damage in a dose-dependent manner. Furthermore, we investigated the potential mechanism(s) of the cardioprotective effect(s) afforded by K5-N,OSepi. In left ventricular samples, I/R induced mast cell degranulation and a robust increase in lipid peroxidation, free radical-induced DNA damage and calcium overload. Markers of neutrophil infiltration and activation were also induced by I/R in rat hearts, specifically myeloperoxidase activity, intercellular-adhesion-molecule-1 expression, prostaglandin-E2 and tumour-necrosis-factor-α production. The robust increase in oxidative stress and inflammatory markers was blunted by K5-N,OSepi, in a dose-dependent manner, with maximum at 1 mg/kg. Furthermore, K5-N,OSepi administration attenuated the increase in caspase 3 activity, Bid and Bax activation and ameliorated the decrease in expression of Bcl-2 within the ischaemic myocardium. In conclusion, we demonstrate that the cardioprotective effect of the non-anticoagulant K5 derivative K5-N,OSepi is secondary to a combination of anti-apoptotic and anti-inflammatory effects. PMID:22248092

  17. Intake of hot water-extracted apple protects against myocardial injury by inhibiting apoptosis in an ischemia/reperfusion rat model.

    PubMed

    Kim, Mi Young; Lim, Sun Ha; Lee, Jongwon

    2014-11-01

    Intakes of apple and its products are shown to reduce the risk of coronary heart disease by delaying occlusion of coronary arteries. In our previous study, we showed that apple pectin protected against myocardial injury by prohibiting apoptotic cascades in a rat model of ischemia/reperfusion. Thus, we hypothesized that water-extracted apple, into which apple pectin was released from the cell wall, might exhibit the same efficacy as apple pectin. To test this hypothesis, we fed rats either cold water- (400 mg kg(-1) d(-1)) or hot water-extracted apples (HWEA; 40, 100, and 400 mg kg(-1) d(-1)). Three days later, the rats were subjected to myocardial injuries by ligating the left anterior descending coronary artery (30 minutes), and subsequently, the heart (3 hours) reperfused by releasing the ligation. Only the rats that were supplemented with HWEA (400 mg kg(-1) d(-1)) showed significant reductions in infarct size, which was 28.5% smaller than that of the control group. This infarct size reduction could be partly attributed to the prevention of steps leading to apoptosis. These steps are manifested by a higher Bcl-2/Bax ratio, lower procaspase-3 conversion to caspase-3, and inhibition of DNA nick generation, which reflects the extent of apoptosis. The findings indicate that HWEA supplementation reduces myocardial injury by inhibiting apoptosis under ischemia/reperfusion conditions. In conclusion, this study suggests that apple intake, specifically boiled apple, might reduce the risk of coronary heart disease by inhibiting postocclusion steps, such as myocardial injury after artery occlusion, as well as preocclusion steps, such as atherosclerotic plaque formation.

  18. Reduced silent information regulator 1 signaling exacerbates myocardial ischemia-reperfusion injury in type 2 diabetic rats and the protective effect of melatonin.

    PubMed

    Yu, Liming; Liang, Hongliang; Dong, Xiaochao; Zhao, Guolong; Jin, Zhenxiao; Zhai, Mengen; Yang, Yang; Chen, Wensheng; Liu, Jincheng; Yi, Wei; Yang, Jian; Yi, Dinghua; Duan, Weixun; Yu, Shiqiang

    2015-10-01

    Diabetes mellitus (DM) increases myocardial oxidative stress and endoplasmic reticulum (ER) stress. Melatonin confers cardioprotective effect by suppressing oxidative damage. However, the effect and mechanism of melatonin on myocardial ischemia-reperfusion (MI/R) injury in type 2 diabetic state are still unknown. In this study, we developed high-fat diet-fed streptozotocin (HFD-STZ) rat, a well-known type 2 diabetic model, to evaluate the effect of melatonin on MI/R injury with a focus on silent information regulator 1 (SIRT1) signaling, oxidative stress, and PERK/eIF2α/ATF4-mediated ER stress. HFD-STZ treated rats were exposed to melatonin treatment in the presence or the absence of sirtinol (a SIRT1 inhibitor) and subjected to MI/R surgery. Compared with nondiabetic animals, type 2 diabetic rats exhibited significantly decreased myocardial SIRT1 signaling, increased apoptosis, enhanced oxidative stress, and ER stress. Additionally, further reduced SIRT1 signaling, aggravated oxidative damage, and ER stress were found in diabetic animals subjected to MI/R surgery. Melatonin markedly reduced MI/R injury by improving cardiac functional recovery and decreasing myocardial apoptosis in type 2 diabetic animals. Melatonin treatment up-regulated SIRT1 expression, reduced oxidative damage, and suppressed PERK/eIF2α/ATF4 signaling. However, these effects were all attenuated by SIRT1 inhibition. Melatonin also protected high glucose/high fat cultured H9C2 cardiomyocytes against simulated ischemia-reperfusion injury-induced ER stress by activating SIRT1 signaling while SIRT1 siRNA blunted this action. Taken together, our study demonstrates that reduced cardiac SIRT1 signaling in type 2 diabetic state aggravates MI/R injury. Melatonin ameliorates reperfusion-induced oxidative stress and ER stress via activation of SIRT1 signaling, thus reducing MI/R damage and improving cardiac function.

  19. Effect of initial temperature changes on myocardial enzyme levels and cardiac function in acute myocardial infarction.

    PubMed

    Qian, Yuanyu; Liu, Jie; Ma, Jinling; Meng, Qingyi; Peng, Chaoying

    2014-07-01

    In the present study, the effect of initial body temperature changes on myocardial enzyme levels and cardiac function in acute myocardial infarction (AMI) patients was investigated. A total of 315 AMI patients were enrolled and the mean temperature was calculated based on their body temperature within 24 h of admission to hospital. The patients were divided into four groups according to their normal body temperature: Group A, <36.5°C; group B, ≥36.5°C and <37.0°C; group C, ≥37.0°C and <37.5°C and group D, ≥37.5°C. The levels of percutaneous coronary intervention, myocardial enzymes and troponin T (TNT), as well as cardiac ultrasound images, were analyzed. Statistically significant differences in the quantity of creatine kinase at 12 and 24 h following admission were identified between group A and groups C and D (P<0.01). A significant difference in TNT at 12 h following admission was observed between groups A and D (P<0.05), however, this difference was not observed with groups B and C. The difference in TNT between the groups at 24 h following admission was not statistically significant (P>0.05). Significant differences in lactate dehydrogenase at 12 and 24 h following admission were observed between groups A and D (P<0.05), however, differences were not observed with groups B and C (P>0.05). Significant differences in glutamic-oxaloacetic transaminase at 12 and 24 h following admission were observed between groups A and D (P<0.05), however, differences were not observed in groups B and C (P>0.05). However, no significant differences were identified in cardiac function index between all the groups. Therefore, the results of the present study indicated that AMI patients with low initial body temperatures exhibited decreased levels of myocardial enzymes and TNT. Thus, the observation of an initially low body temperature may be used as a protective factor for AMI and may improve the existing clinical program.

  20. Development of target-specific liposomes for delivering small molecule drugs after reperfused myocardial infarction.

    PubMed

    Dasa, Siva Sai Krishna; Suzuki, Ryo; Gutknecht, Michael; Brinton, Lindsey T; Tian, Yikui; Michaelsson, Erik; Lindfors, Lennart; Klibanov, Alexander L; French, Brent A; Kelly, Kimberly A

    2015-12-28

    Although reperfusion is essential in restoring circulation to ischemic myocardium, it also leads to irreversible events including reperfusion injury, decreased cardiac function and ultimately scar formation. Various cell types are involved in the multi-phase repair process including inflammatory cells, vascular cells and cardiac fibroblasts. Therapies targeting these cell types in the infarct border zone can improve cardiac function but are limited by systemic side effects. The aim of this work was to develop liposomes with surface modifications to include peptides with affinity for cell types present in the post-infarct myocardium. To identify peptides specific for the infarct/border zone, we used in vivo phage display methods and an optical imaging approach: fluorescence molecular tomography (FMT). We identified peptides specific for cardiomyocytes, endothelial cells, myofibroblasts, and c-Kit + cells present in the border zone of the remodeling infarct. These peptides were then conjugated to liposomes and in vivo specificity and pharmacokinetics were determined. As a proof of concept, cardiomyocyte specific (I-1) liposomes were used to deliver a PARP-1 (poly [ADP-ribose] polymerase 1) inhibitor: AZ7379. Using a targeted liposomal approach, we were able to increase AZ7379 availability in the infarct/border zone at 24h post-injection as compared with free AZ7379. We observed ~3-fold higher efficiency of PARP-1 inhibition when all cell types were assessed using I-1 liposomes as compared with negative control peptide liposomes (NCP). When analyzed further, I-1 liposomes had 9-fold and 1.5-fold higher efficiencies in cardiomyocytes and macrophages, respectively, as compared with NCP liposomes. In conclusion, we have developed a modular drug delivery system that can be targeted to cell types of therapeutic interest in the infarct border zone.

  1. Renoprotective effect of yohimbine on ischaemia/reperfusion-induced acute kidney injury through α2C-adrenoceptors in rats.

    PubMed

    Shimokawa, Takaomi; Tsutsui, Hidenobu; Miura, Takeshi; Nishinaka, Toru; Terada, Tomoyuki; Takama, Masashi; Yoshida, Shuhei; Tanba, Takao; Tojo, Ayumi; Yamagata, Masayo; Yukimura, Tokihito

    2016-06-15

    Excitation of renal sympathetic nervous activity and the resulting increased levels of renal venous norepinephrine play important roles in renal ischaemia/reperfusion injury in rats. This study examined the effects of yohimbine, a non-selective α2-adrenoceptor antagonist, on renal venous norepinephrine levels and kidney function in acute kidney injury. Acute ischaemia/reperfusion-induced kidney injury was induced in rats by clamping the left renal artery and vein for 45min, followed by reperfusion, 2 weeks after a contralateral nephrectomy. Intravenous injection of yohimbine (0.1mg/kg) 5min prior to ischaemia significantly attenuated kidney injury and decreased the renal venous norepinephrine levels, as compared with vehicle-treated rats. To investigate the involvement of α2-adrenoceptor subtypes, we pre-treated with JP-1302, a selective α2C-adrenoceptor antagonist (1mg/kg). This suppressed renal venous norepinephrine levels and tumour necrosis factor-α and monocyte chemoattractant protein-1 mRNA levels after reperfusion and improved kidney function. Pre-treatment with BRL44408, a selective α2A-adrenoceptor antagonist (1mg/kg), or imiloxan, a selective α2B-adrenoceptor antagonist (1mg/kg) had no effect on renal function or tissue injury. These results suggest that yohimbine prevented ischaemia/reperfusion-induced kidney injury by inhibiting α2C-adrenoceptors and suppressing pro-inflammatory cytokine expression.

  2. Trends in Early Aspirin Use Among Patients With Acute Myocardial Infarction in China, 2001–2011: The China PEACE‐Retrospective AMI Study

    PubMed Central

    Gao, Yan; Masoudi, Frederick A.; Hu, Shuang; Li, Jing; Zhang, Haibo; Li, Xi; Desai, Nihar R.; Krumholz, Harlan M.; Jiang, Lixin

    2014-01-01

    Background Aspirin is an effective, safe, and inexpensive early treatment of acute myocardial infarction (AMI) with few barriers to administration, even in countries with limited healthcare resources. However, the rates and recent trends of aspirin use for the early treatment of AMI in China are unknown. Methods and Results Using data from the China Patient‐centered Evaluative Assessment of Cardiac Events Retrospective Study of Acute Myocardial Infarction (China PEACE‐Retrospective AMI Study), we identified a cohort of 14 041 patients with AMI eligible for early aspirin therapy. Early use of aspirin for AMI increased over time (78.4% in 2001, 86.5% in 2006, and 90.0% in 2011). However, about 15% of hospitals had a rate of use of <80% in 2011. Treatment was less likely in patients who were older, presented with cardiogenic shock at admission, presented without chest discomfort, had a final diagnosis of non‐ST‐segment elevation acute myocardial infarction, or did not receive reperfusion therapy. Hospitalization in rural regions was also associated with aspirin underuse. Conclusions Despite improvements in early use of aspirin for AMI in China, there remains marked variation in practice and opportunities for improvement that are concentrated in some hospitals and patient groups. Clinical Trial Registration URL: ClinicalTrials.gov Unique identifier: NCT01624883. PMID:25304853

  3. [The content of selen in blood plasma in patients with acute Q-wave myocardial infarction].

    PubMed

    Radchenko, E N; Nizov, A A; Ivanova, A Yu; Sidorova, Yu S

    2015-01-01

    The level of blood plasma selenium was analyzed by microfluorimetric method in in-patients and out-patients with acute coronary syndrome with ST-elevation resulting in acute Q-wave myocardial infarction. 72 patients, 40-75 years old, with acute Q-wave myocardial infarction were followed during a month. The initial decreased concentration of blood plasma selenium was recorded in most patients in the acute period of the myocardial infarction: deficiency of the microelement (< 90 mcg/l) was found in 30 subjects, the critical ranges (< 70 mcg/l) were stated in 33 patients. Just 2 patients had optimal concentration and 7 patients had a suboptimal one (90-114 mcg/l). Blood plasma level of the microelement increased in 2 weeks after myocardial infarction (in subacute stage) but it was still within deficient or critical levels. No difference was detected in selen concentration depending on gender, age, location on myocardial infarction, accompanying diseases, presence of some risk factors (smoking, alcohol abuse, hereditary predisposition to coronary artery disease). At the same time we revealed a significant Spearman rank correlation in patients with Q-wave myocardial infarction between basal level of blood serum selenium on the one hand, and electrocardiography indices (reflecting the rate of myocardial lesion and necrosis), echocardiography. data (which characterize myocardium reparation processes and remodeling), CPK (a prognostic marker of the myocardial necrosis), HDL-cholesterol (lipid profile index), blood potassium level and BMI on the other.

  4. Magnetic resonance imaging in patients with unstable angina: comparison with acute myocardial infarction and normals

    SciTech Connect

    Ahmad, M.; Johnson, R.F. Jr.; Fawcett, H.D.; Schreiber, M.H.

    1988-09-01

    The role of magnetic resonance imaging in characterizing normal, ischemic and infarcted segments of myocardium was examined in 8 patients with unstable angina, 11 patients with acute myocardial infarction, and 7 patients with stable angina. Eleven normal volunteers were imaged for comparison. Myocardial segments in short axis magnetic resonance images were classified as normal or abnormal on the basis of perfusion changes observed in thallium-201 images in 22 patients and according to the electrocariographic localization of infarction in 4 patients. T2 relaxation time was measured in 57 myocardial segments with abnormal perfusion (24 with reversible and 33 with irreversible perfusion changes) and in 25 normally perfused segments. T2 measurements in normally perfused segments of patients with acute myocardial infarction, unstable angina and stable angina were within normal range derived from T2 measurements in 48 myocardial segments of 11 normal volunteers (42 +/- 10 ms). T2 in abnormal myocardial segments of patients with stable angina also was not significantly different from normal. T2 of abnormal segments in patients with unstable angina (64 +/- 14 in reversibly ischemic and 67 +/- 21 in the irreversibly ischemic segments) was prolonged when compared to normal (p less than 0.0001) and was not significantly different from T2 in abnormal segments of patients with acute myocardial infarction (62 +/- 18 for reversibly and 66 +/- 11 for irreversibly ischemic segments). The data indicate that T2 prolongation is not specific for acute myocardial infarction and may be observed in abnormally perfused segments of patients with unstable angina.

  5. Dexmedetomidine preconditioning may attenuate myocardial ischemia/reperfusion injury by down-regulating the HMGB1-TLR4-MyD88-NF-кB signaling pathway

    PubMed Central

    Zhang, Juan; Meng, Xiao-wen; Ji, Fu-hai

    2017-01-01

    Aims To investigate whether dexmedetomidine (DEX) preconditioning could alleviate the inflammation caused by myocardial ischemia/reperfusion (I/R) injury by reducing HMGB1-TLR4-MyD88-NF-кB signaling. Methods Seventy rats were randomly assigned into five groups: sham group, myocardial I/R group (I/R), DEX+I/R group (DEX), DEX+yohimbine+I/R group (DEX/YOH), and yohimbine+I/R group (YOH). Animals were subjected to 30 min of ischemia induced by occluding the left anterior descending artery followed by 120 min of reperfusion. Myocardial infarct size and histological scores were evaluated. The levels of IL-6 and TNF-α in serum and myocardium were quantified by enzyme-linked immunosorbent assay, and expression of HMGB1, TLR4, MyD88, IκB and NF-κB in the myocardial I/R area were determined with Western blot and immunocytochemistry. Results Myocardial infarct sizes, histological scores, levels of circulating and myocardial IL-6 and TNF-α, the expression of HMGB1, TLR4, MyD88 and NF-κB, and the degradation of IκB were significantly increased in the I/R group compared with the sham group (P<0.01). DEX preconditioning significantly reduced the myocardial infarct size and histological scores (P<0.01 vs. I/R group). Similarly, the serum and myocardial levels of IL-6 and TNF-α, the expression of HMGB1, TLR4, MyD88 and NF-κB, and the degradation of IκB were significantly reduced in the DEX group (P<0.01 vs. I/R group). These effects were partly reversed by yohimbine, a selective α2-adrenergic receptor antagonist, while yohimbine alone had no significant effect on any of the above indicators. Conclusion DEX preconditioning reduces myocardial I/R injury in part by attenuating inflammation, which may be attributed to the downregulation of the HMGB1-TLR4-MyD88-NF-кB signaling pathway mediated by the α2-adrenergic receptor activation. PMID:28222157

  6. Antiphospholipid Syndrome - A Case Report of Pulmonary Thromboembolism, Followed with Acute Myocardial Infarction in Patient with Systemic Sclerosis

    PubMed Central

    Vavlukis, Marija; Kotlar, Irina; Chaparoska, Emilija; Pocesta, Bekim; Pejkov, Hristo; Boshev, Marjan; Kedev, Sasko

    2015-01-01

    AIM: We are presenting an uncommon case of pulmonary embolism, followed with an acute myocardial infarction, in a patient with progressive systemic sclerosis. CASE PRESENTATION: A female 40 years of age was admitted with signs of pulmonary embolism, confirmed with CT scan, which also reviled a thrombus in the right ventricle. The patient had medical history of systemic sclerosis since the age of 16 years. She suffered an ischemic stroke 6 years ago, but she was not taking any anticoagulant or antithrombotic medications ever since. She received a treatment with thrombolytic therapy, and subsequent UFH, but, on the second day after receiving fibrinolysis, she felt chest pain accompanied with ECG changes consistent for ST-segment elevation myocardial infarction (STEMI). Urgent coronary angiography was undertaken, which reviled cloths causing total occlusion in 4 blood vessels, followed with thromboaspiration, but without successful reperfusion. Several hours later the patient developed rapid deterioration with letal ending. During the very short hospital course, blood sampling reviled presence of antiphospholipid antibodies. CONCLUSION: The acquired antiphospholipid syndrome is common condition in patients with systemic autoimmune diseases, but relatively rare in patients with systemic sclerosis. Never the less, we have to be aware of it when treating the patients with systemic sclerosis. PMID:27275312

  7. Quality indicators for acute myocardial infarction: A position paper of the Acute Cardiovascular Care Association.

    PubMed

    Schiele, Francois; Gale, Chris P; Bonnefoy, Eric; Capuano, Frederic; Claeys, Marc J; Danchin, Nicolas; Fox, Keith Aa; Huber, Kurt; Iakobishvili, Zaza; Lettino, Maddalena; Quinn, Tom; Rubini Gimenez, Maria; Bøtker, Hans E; Swahn, Eva; Timmis, Adam; Tubaro, Marco; Vrints, Christiaan; Walker, David; Zahger, Doron; Zeymer, Uwe; Bueno, Hector

    2017-02-01

    Evaluation of quality of care is an integral part of modern healthcare, and has become an indispensable tool for health authorities, the public, the press and patients. However, measuring quality of care is difficult, because it is a multifactorial and multidimensional concept that cannot be estimated solely on the basis of patients' clinical outcomes. Thus, measuring the process of care through quality indicators (QIs) has become a widely used practice in this context. Other professional societies have published QIs for the evaluation of quality of care in the context of acute myocardial infarction (AMI), but no such indicators exist in Europe. In this context, the European Society of Cardiology (ESC) Acute Cardiovascular Care Association (ACCA) has reflected on the measurement of quality of care in the context of AMI (ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI)) and created a set of QIs, with a view to developing programmes to improve quality of care for the management of AMI across Europe. We present here the list of QIs defined by the ACCA, with explanations of the methodology used, scientific justification and reasons for the choice for each measure.

  8. Protective Effect of N-Acetylserotonin against Acute Hepatic Ischemia-Reperfusion Injury in Mice

    PubMed Central

    Yu, Shuna; Zheng, Jie; Jiang, Zhengchen; Shi, Caixing; Li, Jin; Du, Xiaodong; Wang, Hailiang; Jiang, Jiying; Wang, Xin

    2013-01-01

    The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury. PMID:23994834

  9. Octreotide Attenuates Acute Kidney Injury after Hepatic Ischemia and Reperfusion by Enhancing Autophagy

    PubMed Central

    Sun, Huiping; Zou, Shuangfa; Candiotti, Keith A.; Peng, Yanhua; Zhang, Qinya; Xiao, Weiqiang; Wen, Yiyun; wu, Jiao; Yang, Jinfeng

    2017-01-01

    Octreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat. Octreotide pretreatment significantly preserved renal function and reduced the severity of renal injury. Moreover, octreotide alleviated inflammation and apoptosis in the kidney after HIR. Additionally, octreotide induced autophagy and autophagy inhibition with 3MA markedly reversed the renoprotective, anti-inflammatory and anti-apoptotic effects of octreotide after HIR. Finally, octreotide abrogated the activation of phosphorylation of Akt, mTOR and p70S6K in the kidney after HIR. Our results indicate that octreotide reduced renal injury after HIR due to its induction of autophagy. The enhancement of autophagy may be potentially linked to the octreotide mediated Akt/mTOR/p70S6K pathway deactivation and reduction of kidney inflammation and apoptosis after HIR. PMID:28205545

  10. Berberine reduces ischemia/reperfusion-induced myocardial apoptosis via activating AMPK and PI3K-Akt signaling in diabetic rats.

    PubMed

    Chen, Keke; Li, Guohua; Geng, Fenghao; Zhang, Zhao; Li, Jiani; Yang, Min; Dong, Ling; Gao, Feng

    2014-06-01

    Diabetes increases the risk of cardiovascular diseases. Berberine (BBR), an isoquinoline alkaloid used in Chinese medicine, exerts anti-diabetic effect by lowering blood glucose and regulating lipid metabolism. It has been reported that BBR decreases mortality in patients with chronic congestive heart failure. However, the molecular mechanisms of these beneficial effects are incompletely understood. In the present study, we sought to determine whether BBR exerts cardioprotective effect against ischemia/reperfusion (I/R) injury in diabetic rats and the underlying mechanisms. Male Sprague-Dawley rats were injected with low dose streptozotocin and fed with a high-fat diet for 12 weeks to induce diabetes. The diabetic rats were intragastrically administered with saline or BBR (100, 200 and 400 mg/kg/d) starting from week 9 to 12. At the end of week 12, all rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion. BBR significantly improved the recovery of cardiac systolic/diastolic function and reduced myocardial apoptosis in diabetic rats subjected to myocardial I/R. Furthermore, in cultured neonatal rat cardiomyocytes, BBR (50 μmol/L) reduced hypoxia/reoxygenation-induced myocardial apoptosis, increased Bcl-2/Bax ratio and decreased caspase-3 expression, together with enhanced activation of PI3K-Akt and increased adenosine monophosphate-activated protein kinase (AMPK) and eNOS phosphorylation. Pretreatment with either PI3K/Akt inhibitor wortmannin or AMPK inhibitor Compound C blunted the anti-apoptotic effect of BBR. Our findings demonstrate that BBR exerts anti-apoptotic effect and improves cardiac functional recovery following myocardial I/R via activating AMPK and PI3K-Akt-eNOS signaling in diabetic rats.

  11. Acute myocardial injury caused by Sydney funnel-web spider (Atrax robustus) envenoming.

    PubMed

    Isbister, G K; Warner, G

    2003-12-01

    A 67-year-old female suffered envenoming by a Sydney funnel-web spider (Atrax robustus), complicated by ST elevation and elevated troponin levels consistent with an acute myocardial injury. She was treated primarily with funnel-web spider antivenom, admission to intensive care and initial respiratory support for acute pulmonary oedema. The mechanism by which funnel-web spider envenomation caused myocardial injury is unclear but follow-up nuclear studies in the patient demonstrated that she had minimal atherosclerotic disease.

  12. Takotsubo cardiomyopathy after acute myocardial infarction: An unusual case of possible association.

    PubMed

    Ferrara, Francesco; Baldi, Cesare; Malinconico, Marisa; Acri, Edvige; Cirillo, Annapaola; Citro, Rodolfo; Bossone, Eduardo

    2016-04-01

    Takotsubo cardiomyopathy is an acute reversible clinical condition mimicking an acute myocardial infarction. Although a normal coronary artery tree is frequently detected, the concurrence of coronary artery disease is a common finding in a substantial proportion of patients. We report an unusual case of takotsubo cardiomyopathy in post-menopausal women after emotional stress, occurring after inferior ST-segment elevation myocardial infarction. The possible association between takotsubo cardiomyopathy and coronary artery disease is discussed.

  13. Acute Myocardial Infarction Due to Spontaneous Dissection of the Right Coronary Artery in a Young Male

    SciTech Connect

    Papadopoulos, Dimitris P. Moyssakis, Ioannis; Perakis, Alexandros; Athanasiou, Andreas; Anagnostopoulou, Sophia; Benos, Ioannis; Votteas, Vassilios E.

    2004-09-15

    Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction. We report a case of a 33-year-old male who presented with an acute inferior myocardial infarction. Coronary arteriography performed 3 hours after the episode revealed a dissection involving the middle segment of right coronary artery. Because of a spiral form of dissection and the TIMI 3 flow grade, our patient was treated medically and repeat coronary angiography 6 months later was decided.

  14. Effects of preconditioning on reperfusion arrhythmias, myocardial functions, formation of free radicals, and ion shifts in isolated ischemic/reperfused rat hearts.

    PubMed

    Tosaki, A; Cordis, G A; Szerdahelyi, P; Engelman, R M; Das, D K

    1994-03-01

    The effects of preconditioning on development of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT), free radical formation, and ion shifts, particularly those of Na, K, Ca, and Mg, were studied in isolated rat heart. Hearts were randomly divided into four groups: group I, aerobically perfused time-matched controls with no preconditioning or ischemia; group II, hearts subjected to 30-min global ischemia followed by 30-min reperfusion; group III, hearts subjected to one cycle of preconditioning, consisting of 5-min global ischemia plus 10-min reperfusion, followed by 30-min global ischemia plus 30-min reperfusion; and group IV, hearts subjected to four cycles of preconditioning (5-min ischemia plus 10-min reperfusion) followed by 30-min ischemia plus 30-min reperfusion. The incidences of VF and VT were reduced from their nonpreconditioned ischemic values of 100 and 100% in group II to 83 and 92% in group III and to 33% (p < 0.05) and 41% (p < 0.05) in group IV, respectively. Maximum malondialdehyde formation, as an indirect marker of free radicals, was observed after 30-min ischemia followed by 10-min reperfusion (0.72 +/- 0.1 nmol/ml) in the nonpreconditioned ischemic group (protocol II). One and four cycles of preconditioning reduced formation of malondialdehyde from the nonpreconditioned ischemic value of 0.72 +/- 0.1 to 0.35 +/- 0.02 and 0.26 +/- 0.02 nmol/ml (p < 0.05), respectively. The same trend was observed when free radical formation was directly detected by salicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Left ventricular muscle and fluid mechanics in acute myocardial infarction.

    PubMed

    Nucifora, Gaetano; Delgado, Victoria; Bertini, Matteo; Marsan, Nina Ajmone; Van de Veire, Nico R; Ng, Arnold C T; Siebelink, Hans-Marc J; Schalij, Martin J; Holman, Eduard R; Sengupta, Partho P; Bax, Jeroen J

    2010-11-15

    Left ventricular (LV) diastolic filling is characterized by the formation of intraventricular rotational bodies of fluid (termed "vortex rings") that optimize the efficiency of LV ejection. The aim of the present study was to evaluate the morphology and dynamics of LV diastolic vortex ring formation early after acute myocardial infarction (AMI), in relation to LV diastolic function and infarct size. A total of 94 patients with a first ST-segment elevation AMI (59 ± 11 years; 78% men) were included. All patients underwent primary percutaneous coronary intervention. After 48 hours, the following examinations were performed: 2-dimensional echocardiography with speckle-tracking analysis to assess the LV systolic and diastolic function, the vortex formation time (VFT, a dimensionless index for characterizing vortex formation), and the LV untwisting rate; contrast echocardiography to assess LV vortex morphology; and myocardial contrast echocardiography to identify the infarct size. Patients with a large infarct size (≥ 3 LV segments) had a significantly lower VFT (p <0.001) and vortex sphericity index (p <0.001). On univariate analysis, several variables were significantly related to the VFT, including anterior AMI, LV end-systolic volume, LV ejection fraction, grade of diastolic dysfunction, LV untwisting rate, and infarct size. On multivariate analysis, the LV untwisting rate (β = -0.43, p <0.001) and infarct size (β = -0.33, p = 0.005) were independently associated with VFT. In conclusion, early in AMI, both the LV infarct size and the mechanical sequence of diastolic restoration play key roles in modulating the morphology and dynamics of early diastolic vortex ring formation.

  16. [Myocardial infarction and acute coronary syndrome: definitions, classification, and diagnostic criteria].

    PubMed

    Zaĭrat'iants, O V; Mishnev, O D; Kakturskiĭ, L V

    2014-01-01

    The review gives the definitions and classification of and diagnostic criteria for myocardial infarction and acute coronary syndrome in accordance with the "The third universal definition of myocardial infarction" adopted in 2012 (Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, 2012). It also discusses the clinical and morphological comparisons of and the problems in the differential diagnosis of myocardial infarction as a nosological entity within coronary heart disease with other coronarogenic and non-coronarogenic necroses of the myocardium.

  17. Validation of the Killip-Kimball Classification and Late Mortality after Acute Myocardial Infarction

    PubMed Central

    de Mello, Bruno Henrique Gallindo; Oliveira, Gustavo Bernardes F.; Ramos, Rui Fernando; Lopes, Bernardo Baptista C.; Barros, Cecília Bitarães S.; Carvalho, Erick de Oliveira; Teixeira, Fabio Bellini P.; Arruda, Guilherme D'Andréa S.; Revelo, Maria Sol Calero; Piegas, Leopoldo Soares

    2014-01-01

    Background The classification or index of heart failure severity in patients with acute myocardial infarction (AMI) was proposed by Killip and Kimball aiming at assessing the risk of in-hospital death and the potential benefit of specific management of care provided in Coronary Care Units (CCU) during the decade of 60. Objective To validate the risk stratification of Killip classification in the long-term mortality and compare the prognostic value in patients with non-ST-segment elevation MI (NSTEMI) relative to patients with ST-segment elevation MI (STEMI), in the era of reperfusion and modern antithrombotic therapies. Methods We evaluated 1906 patients with documented AMI and admitted to the CCU, from 1995 to 2011, with a mean follow-up of 05 years to assess total mortality. Kaplan-Meier (KM) curves were developed for comparison between survival distributions according to Killip class and NSTEMI versus STEMI. Cox proportional regression models were developed to determine the independent association between Killip class and mortality, with sensitivity analyses based on type of AMI. Results: The proportions of deaths and the KM survival distributions were significantly different across Killip class >1 (p <0.001) and with a similar pattern between patients with NSTEMI and STEMI. Cox models identified the Killip classification as a significant, sustained, consistent predictor and independent of relevant covariables (Wald χ2 16.5 [p = 0.001], NSTEMI) and (Wald χ2 11.9 [p = 0.008], STEMI). Conclusion The Killip and Kimball classification performs relevant prognostic role in mortality at mean follow-up of 05 years post-AMI, with a similar pattern between NSTEMI and STEMI patients. PMID:25014060

  18. Exercise capacity in patients 3 days after acute, uncomplicated myocardial infarction

    SciTech Connect

    Burek, K.A.; Kirscht, J.; Topol, E.J. )

    1989-11-01

    In a randomized, controlled trial of early hospital discharge after acute myocardial infarction (MI), a heart rate, symptom-limited exercise thallium test was performed after the onset of MI. Patients' exercise capacity was evaluated by the exercise treadmill with accompanying thallium scintigraphy. Of 507 consecutive patients screened, the condition of 179 was classified as uncomplicated, which is defined as the absence of angina, heart failure, or serious arrhythmias at 72 hours from admission. Of the patients with uncomplicated conditions, 126 had an exercise test on day 3 and 53 did not exercise on day 3. Of the 126 patients who exercised on day 3, 36 had a positive test and 90 had a negative test for ischemia. The 36 patients with a positive test result exercised a mean time of 6.71 +/- 2.8 minutes, achieved a mean peak heart rate of 120.9 +/- 21.4 beats/min, reached a peak systolic blood pressure of 144.7 +/- 33.3 mm Hg, and achieved a double product (rate-pressure product) of 183.4 +/- 67.6. The 90 patients with a negative test result for ischemia exercised 9.45 +/- 12.7 minutes, achieved a peak heart rate of 130.2 +/- 14.4 beats/min, reached a mean systolic blood pressure of 155.5 +/- 29.4 mm Hg, and achieved a rate-pressure product of 210.5 +/- 44.0. Of the 90 patients with uncomplicated conditions who had a negative exercise test for ischemia, 85 patients received reperfusion therapy, which included thrombolysis or coronary angioplasty or both.

  19. Activation of the contact system and inflammation after thrombolytic therapy in patients with acute myocardial infarction.

    PubMed

    Merlini, Piera Angelica; Cugno, Massimo; Rossi, Marco L; Agricola, Pietro; Repetto, Alessandra; Fetiveau, Raffaella; Diotallevi, Paolo; Canosi, Umberto; Mannucci, Pier Mannuccio; Ardissino, Diego

    2004-04-01

    Thrombolytic therapy activates the contact system, and factor XII activation may activate the coagulation cascade and inflammation. It is not known whether an early inflammatory response is induced by thrombolytic therapy in patients with acute myocardial infarction (AMI). We prospectively measured the plasma levels of activated factor XII, cleaved kininogen, prothrombin fragment 1 + 2 (as indexes of the contact phase and coagulation activation), and interleukin-6 and C-reactive protein (CRP) (as indexes of inflammation) in 39 patients hospitalized for AMI within 12 hours of symptom onset: 26 receiving thrombolytic therapy and 13 heparin alone. Blood samples were collected at baseline and after 90 minutes and 24 hours. Patients undergoing thrombolysis had a significant early increase in activated factor XII (from 2.2 ng/ml at baseline to 4.7 ng/ml after 90 minutes; p = 0.0001), cleaved kininogen (from 26% to 37%; p = 0.001), and fragment 1 + 2 (from 1.4 to 2.1 nmol/L; p = 0.0001), whereas the 24-hour levels were similar to baseline levels. The levels of interleukin-6 significantly increased during the first 90 minutes (from 3.9 to 6.3 microg/ml; p = 0.001), and were even higher after 24 hours (11.9 ng/ml, p = 0.0001). CRP levels increased only after 24 hours (p = 0.0001). There were no changes in these parameters in patients receiving heparin alone, except for a 24-hour increase in interleukin-6 and CRP levels. Thus, in patients with AMI receiving thrombolytic therapy, early activation of inflammation parallels the activation of the contact system and the coagulation cascade, which might contribute to microvascular obstruction and reperfusion injury.

  20. The clinical challenge of preventing sudden cardiac death immediately after acute ST-elevation myocardial infarction.

    PubMed

    Manolis, Antonis S

    2014-12-01

    Unfortunately, of all patients experiencing acute myocardial infarction (MI), usually in the form of ST-elevation MI, 25-35% will die of sudden cardiac death (SCD) before receiving medical attention, most often from ventricular fibrillation. For patients who reach the hospital, prognosis is considerably better and has improved over the years. Reperfusion therapy, best attained with primary percutaneous coronary intervention compared to thrombolysis, has made a big difference in reducing the risk of SCD early and late after ST-elevation MI. In-hospital SCD due to ventricular tachyarrhythmias is manageable, with either preventive measures or drugs or electrical cardioversion. There is general agreement for secondary prevention of SCD post-MI with implantation of a cardioverter defibrillator (ICD) when malignant ventricular arrhythmias occur late (>48 h) after an MI, and are not due to reversible or correctable causes. The major challenge remains that of primary prevention, that is, how to prevent SCD during the first 1-3 months after ST-elevation MI for patients who have low left ventricular ejection fraction and are not candidates for an ICD according to current guidelines, due to the results of two studies, which did not show any benefits of early (<40 days after an MI) ICD implantation. Two recent documents may provide direction as to how to bridge the gap for this early post-MI period. Both recommend an electrophysiology study to guide implantation of an ICD, at least for those developing syncope or non-sustained ventricular tachycardia, who have an inducible sustained ventricular tachycardia at the electrophysiology study. An ICD is also recommended for patients with indication for a permanent pacemaker due to bradyarrhythmias, who also meet primary prevention criteria for SCD.

  1. Multiparametric Magnetic Resonance Imaging for Prediction of Parenchymal Hemorrhage in Acute Ischemic Stroke After Reperfusion Therapy

    PubMed Central

    R. Knitter, James; Jahan, Reza; Gornbein, Jeffery; Ajani, Zahra; Feng, Lei; Meyer, Brett C.; Schwamm, Lee H.; Yoo, Albert J.; Marshall, Randolph S.; Meyers, Philip M.; Yavagal, Dileep R.; Wintermark, Max; Liebeskind, David S.; Guzy, Judy; Starkman, Sidney; Saver, Jeffrey L.; Kidwell, Chelsea S.

    2017-01-01

    Background and Purpose— Patients with acute ischemic stroke are at increased risk of developing parenchymal hemorrhage (PH), particularly in the setting of reperfusion therapies. We have developed a predictive model to examine the risk of PH using combined magnetic resonance perfusion and diffusion parameters, including cerebral blood volume (CBV), apparent diffusion coefficient, and microvascular permeability (K2). Methods— Voxel-based values of CBV, K2, and apparent diffusion coefficient from the ischemic core were obtained using pretreatment magnetic resonance imaging data from patients enrolled in the MR RESCUE clinical trial (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy). The associations between PH and extreme values of imaging parameters were assessed in univariate and multivariate analyses. Receiver-operating characteristic curve analysis was performed to determine the optimal parameter(s) and threshold for predicting PH. Results— In 83 patients included in this analysis, 20 developed PH. Univariate analysis showed significantly lower 10th percentile CBV and 10th percentile apparent diffusion coefficient values and significantly higher 90th percentile K2 values within the infarction core of patients with PH. Using classification tree analysis, the 10th percentile CBV at threshold of 0.47 and 90th percentile K2 at threshold of 0.28 resulted in overall predictive accuracy of 88.7%, sensitivity of 90.0%, and specificity of 87.3%, which was superior to any individual or combination of other classifiers. Conclusions— Our results suggest that combined 10th percentile CBV and 90th percentile K2 is an independent predictor of PH in patients with acute ischemic stroke with diagnostic accuracy superior to individual classifiers alone. This approach may allow risk stratification for patients undergoing reperfusion therapies. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT00389467. PMID

  2. Myocardial protection of early extracorporeal membrane oxygenation (ECMO) support for acute myocardial infarction with cardiogenic shock in pigs.

    PubMed

    Zhu, Gang-jie; Sun, Li-na; Li, Xing-hai; Wang, Ning-fu; Wu, Hong-hai; Yuan, Chen-xing; Li, Qiao-qiao; Xu, Peng; Ren, Ya-qi; Mao, Bao-gen

    2015-09-01

    The aim of this study was to explore myocardial protection of early extracorporeal membrane oxygenation (ECMO) support for acute myocardial infarction with cardiogenic shock in pigs. 24 male pigs (34.6 ± 1.3 kg) were randomly divided into three groups-control group, drug therapy group, and ECMO group. Myocardial infarction model was created in drug therapy group and ECMO group by ligating coronary artery. When cardiogenic shock occurred, drugs were given in drug therapy group and ECMO began to work in ECMO group. The pigs were killed 24 h after cardiogenic shock. Compared with in drug therapy group, left ventricular end-diastolic pressure in ECMO group decreased significantly 6 h after ligation (P < 0.05). At the end of the experiments, LV - dp/dt among three groups was significantly different, drug therapy group < ECMO group < control group. There was no difference in LV + dp/dt between drug therapy group and ECMO group. Compared with drug group, myocardial infarct size of ECMO group did not reduce significantly, but myocardial enzyme and troponin-I decreased significantly. Compared with drug therapy, ECMO improves left ventricular diastolic function, and may improve systolic function. ECMO cannot reduce myocardial infarct size without revascularization, but may have positive effects on ischemic areas by avoiding further injuring.

  3. Prognostic implications of cardiac scintigraphic parameters obtained in the early phase of acute myocardial infarction

    SciTech Connect

    Suzuki, A.; Matsushima, H.; Satoh, A.; Hayashi, H.; Sotobata, I.

    1988-06-01

    A cohort of 76 patients with acute myocardial infarction was studied with infarct-avid scan, radionuclide ventriculography, and thallium-201 myocardial perfusion scintigraphy. Infarct area, left ventricular ejection fraction, and defect score were calculated as radionuclide indices of the extent of myocardial infarction. The correlation was studied between these indices and cardiac events (death, congestive heart failure, postinfarction angina, and recurrence of myocardial infarction) in the first postinfarction year. High-risk patients (nonsurvivors and patients who developed heart failure) had a larger infarct area, a lower left ventricular ejection fraction, and a larger defect score than the others. Univariate linear discriminant analysis was done to determine the optimal threshold of these parameters for distinguishing high-risk patients from others. Radionuclide parameters obtained in the early phase of acute myocardial infarction were useful for detecting both patients with grave complications and those with poor late prognosis during a mean follow-up period of 2.6 years.

  4. The role of ADAMTS13 in acute myocardial infarction: cause or consequence?

    PubMed Central

    Eerenberg, Elise S.; Teunissen, Paul F.A.; van den Born, Bert-Jan; Meijers, Joost C.M.; Hollander, Maurits R.; Jansen, Matthijs; Tijssen, Ruben; Beliën, Jeroen A.M.; van de Ven, Peter M.; Aly, Mohamed F.; Kamp, Otto; Niessen, Hans W.; Kamphuisen, Pieter Willem; Levi, Marcel; van Royen, Niels

    2016-01-01

    Aims ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, is a metalloprotease that cleaves von Willebrand factor (VWF). There is considerable evidence that VWF levels increase and ADAMTS13 levels decrease in ST-elevation myocardial infarction (STEMI) patients. It is unclear whether this contributes to no reflow, infarct size, and intramyocardial haemorrhage (IMH). We aimed to determine the role of ADAMTS13 in STEMI patients and to investigate the benefits of recombinant ADAMTS13 (rADAMTS13) in a porcine model of myocardial ischaemia-reperfusion. Methods and results In 49 consecutive percutaneous coronary intervention (PCI)-treated STEMI patients, blood samples were collected directly after through 7 days following PCI. Cardiac magnetic resonance was performed 4–6 days after PCI to determine infarct size and IMH. In 23 Yorkshire swine, the circumflex coronary artery was occluded for 75 min. rADAMTS13 or vehicle was administered intracoronary following reperfusion. Myocardial injury and infarct characteristics were assessed using cardiac enzymes, ECG, and histopathology. In patients with IMH, VWF activity and VWF antigen were significantly elevated directly after PCI and for all subsequent measurements, and ADAMTS13 activity significantly decreased at 4 and 7 days following PCI, in comparison with patients without IMH. VWF activity and ADAMTS13 activity were not related to infarct size. In rADAMTS13-treated animals, no differences in infarct size, IMH, or formation of microthrombi were witnessed compared with controls. Conclusions No correlation was found between VWF/ADAMTS13 and infarct size in patients. However, patients suffering from IMH had significantly higher VWF activity and lower ADAMTS13 activity. Intracoronary administration of rADAMTS13 did not decrease infarct size or IMH in a porcine model of myocardial ischaemia-reperfusion. These data dispute the imbalance in ADAMTS13 and VWF as the cause of no reflow. PMID

  5. Dysferlin Mediates the Cytoprotective Effects of TRAF2 Following Myocardial Ischemia Reperfusion Injury

    PubMed Central

    Tzeng, Huei‐Ping; Evans, Sarah; Gao, Feng; Chambers, Kari; Topkara, Veli K.; Sivasubramanian, Natarajan; Barger, Philip M.; Mann, Douglas L.

    2014-01-01

    Background We have demonstrated that tumor necrosis factor (TNF) receptor‐associated factor 2 (TRAF2), a scaffolding protein common to TNF receptors 1 and 2, confers cytoprotection in the heart. However, the mechanisms for the cytoprotective effects of TRAF2 are not known. Methods/Results Mice with cardiac‐restricted overexpression of low levels of TRAF2 (MHC‐TRAF2LC) and a dominant negative TRAF2 (MHC‐TRAF2DN) were subjected to ischemia (30‐minute) reperfusion (60‐minute) injury (I/R), using a Langendorff apparatus. MHC‐TRAF2LC mice were protected against I/R injury as shown by a significant ≈27% greater left ventricular (LV) developed pressure after I/R, whereas mice with impaired TRAF2 signaling had a significantly ≈38% lower LV developed pressure, a ≈41% greater creatine kinase (CK) release, and ≈52% greater Evans blue dye uptake after I/R, compared to LM. Transcriptional profiling of MHC‐TRAF2LC and MHC‐TRAF2DN mice identified a calcium‐triggered exocytotic membrane repair protein, dysferlin, as a potential cytoprotective gene responsible for the cytoprotective effects of TRAF2. Mice lacking dysferlin had a significant ≈39% lower LV developed pressure, a ≈20% greater CK release, and ≈29% greater Evans blue dye uptake after I/R, compared to wild‐type mice, thus phenocopying the response to tissue injury in the MHC‐TRAF2DN mice. Moreover, breeding MHC‐TRAF2LC onto a dysferlin‐null background significantly attenuated the cytoprotective effects of TRAF2 after I/R injury. Conclusion The study shows that dysferlin, a calcium‐triggered exocytotic membrane repair protein, is required for the cytoprotective effects of TRAF2‐mediated signaling after I/R injury. PMID:24572254

  6. Sex differences in ischaemia/reperfusion-induced acute kidney injury depends on the degradation of noradrenaline by monoamine oxidase.

    PubMed

    Tanaka, Ryosuke; Yazawa, Maki; Morikawa, Yuri; Tsutsui, Hidenobu; Ohkita, Mamoru; Yukimura, Tokihito; Matsumura, Yasuo

    2017-03-01

    Ischaemic acute kidney injury (AKI) is a leading killer of both sexes; however, resistance to this injury is higher among women than men. We found that renal venous noradrenaline (NAd) overflow after reperfusion played important roles in the development of ischaemic AKI, and that the attenuation of AKI observed in female rats may be dependent on depressing the renal sympathetic nervous system with endogenous oestrogen. In the present study, we used male and female Sprague-Dawley rats to investigate whether sex differences in the pathogenesis of ischaemic AKI are related to the degradation of NAd by monoamine oxidase (MAO) in the kidney. Ischaemic AKI was achieved by clamping the left renal artery and vein for 45 minutes followed by reperfusion 2 weeks after contralateral nephrectomy. Renal injury was more severe in male rats than in female rats and renal venous plasma NAd levels after reperfusion were markedly elevated in males, but not in females. These sex differences were eliminated by a treatment with isatin, a non-selective MAO inhibitor, and moclobemide, a selective MAOA inhibitor, but not by selegiline, a selective MAOB inhibitor. Ischaemia decreased the mRNA expression levels of both MAOs in the kidney 1 day after reperfusion; however, MAOA mRNA expression levels were higher in female rats than in male rats. These results suggest that the degradation of NAd by MAOA in the kidney contributes to sex differences in the pathogenesis of ischaemia/reperfusion-induced AKI.

  7. A novel laser-Doppler flowmetry assisted murine model of acute hindlimb ischemia-reperfusion for free flap research.

    PubMed

    Sönmez, Tolga Taha; Al-Sawaf, Othman; Brandacher, Gerald; Kanzler, Isabella; Tuchscheerer, Nancy; Tohidnezhad, Mersedeh; Kanatas, Anastasios; Knobe, Matthias; Fragoulis, Athanassios; Tolba, René; Mitchell, David; Pufe, Thomas; Wruck, Christoph Jan; Hölzle, Frank; Liehn, Elisa Anamaria

    2013-01-01

    Suitable and reproducible experimental models of translational research in reconstructive surgery that allow in-vivo investigation of diverse molecular and cellular mechanisms are still limited. To this end we created a novel murine model of acute hindlimb ischemia-reperfusion to mimic a microsurgical free flap procedure. Thirty-six C57BL6 mice (n = 6/group) were assigned to one control and five experimental groups (subject to 6, 12, 96, 120 hours and 14 days of reperfusion, respectively) following 4 hours of complete hindlimb ischemia. Ischemia and reperfusion were monitored using Laser-Doppler Flowmetry. Hindlimb tissue components (skin and muscle) were investigated using histopathology, quantitative immunohistochemistry and immunofluorescence. Despite massive initial tissue damage induced by ischemia-reperfusion injury, the structure of the skin component was restored after 96 hours. During the same time, muscle cells were replaced by young myotubes. In addition, initial neuromuscular dysfunction, edema and swelling resolved by day 4. After two weeks, no functional or neuromuscular deficits were detectable. Furthermore, upregulation of VEGF and tissue infiltration with CD34-positive stem cells led to new capillary formation, which peaked with significantly higher values after two weeks. These data indicate that our model is suitable to investigate cellular and molecular tissue alterations from ischemia-reperfusion such as occur during free flap procedures.

  8. The role of excessive versus acute administration of erythropoietin in attenuating hepatic ischemia-reperfusion injury.

    PubMed

    Pappo, Orit; Ben-Ari, Ziv; Shevtsov, Evgeni; Avlas, Orna; Gassmann, Max; Ravid, Amiram; Cheporko, Yelena; Hochhauser, Edith

    2010-12-01

    Ischemia-reperfusion injury (I/R) is the main cause of primary graft nonfunction. Our aim was to evaluate the effect of excessive versus acute administration of erythropoietin (EPO) in attenuating the hepatic injury induced by I/R in mice. The effect of segmental (70%) hepatic ischemia was evaluated in a transgenic mouse line with constitutive overexpression of human EPO cDNA and in wild-type (WT) mice. Mice were randomly allocated to 5 main experimental groups: (i) WT-sham, (ii) WT ischemia, (iii) WT ischemia + recombinant human erythropoietin (rhEPO), (iv) transgenic-sham, and (v) transgenic ischemia. The EPO-pretreated mice showed a significant reduction in liver enzyme levels and intrahepatic caspase-3 activity and fewer apoptotic hepatocytes (p < 0.05 for all) compared with the WT untreated I/R group. EPO decreased c-Jun N-terminal kinase (JNK) phosphorylation and nuclear factor-κB (NF-κB) expression during I/R. In transgenic I/R livers, baseline histology showed diffused hepatic injury, and no significant beneficial effect was noted between the WT untreated and the transgenic I/R mice. In conclusion, acute pretreatment with EPO in WT mice attenuated in vivo I/R liver injury. However, in excessive EPO overexpression, the initial liver injury abolished the beneficial effect of EPO. These findings have important implications for the potential use of acute EPO in I/R injury during liver transplantation.

  9. Myocardial uptake of indium-111-labeled antimyosin in acute subendocardial infarction: Clinical, histochemical, and autoradiographic correlation of myocardial necrosis

    SciTech Connect

    Hendel, R.C.; McSherry, B.A.; Leppo, J.A. )

    1990-11-01

    Indium-111-labeled antimyosin has been utilized in the diagnosis and localization of acute transmural myocardial infarction. The present report describes a patient who presented with a massive subendocardial infarction. Two days after the injection of antimyosin, the patient's clinical status markedly deteriorated and he expired. Postmortem examination demonstrated severe three-vessel coronary artery disease with extensive myocyte death in the endocardium. Autoradiography and histochemical staining of the prosected heart demonstrated high correlation for myocardial necrosis and corresponded to clinical evidence for diffuse subendocardial infarction.

  10. Acute myocardial infarction after heart irradiation in young patients with Hodgkin's disease

    SciTech Connect

    Joensuu, H.

    1989-02-01

    Forty-seven patients younger than 40 years at the time of the diagnosis, and irradiated to the mediastinum for Hodgkin's disease at Turku University Central Hospital from 1977 to 1982, were regularly followed for 56 to 127 months after therapy. Two patients developed an acute myocardial infarction ten and 50 months after cardiac irradiation at the age of only 28 and 24 years, respectively. None of the patients died from lymphoma within five years from the diagnosis, but one of the infarctions was eventually fatal. Since acute myocardial infarction is rare in this age group, the result suggests strongly that prior cardiac irradiation is a risk factor for acute myocardial infarction. The possibility of radiation-induced myocardial infarction should be taken into account both in treatment planning and follow-up of patients with Hodgkin's disease.

  11. An unusual case of silent acute ST-elevation myocardial infarction following amphetamine use.

    PubMed

    Chia-Yu Chang, Julia; Peng, Chian-Ze; How, Chorng-Kuang; Huang, Mu-Shun

    2013-07-01

    We report a case of silent acute ST-elevation myocardial infarction associated with amphetamine use in a 62 years old diabetic man. The patient was devoid of chest pain and had a normal cardiac enzyme analysis at the initial presentation. A routine electrocardiogram demonstrated acute inferior wall ST-elevation myocardial infarction. Coronary angiography confirmed a total occlusion of the posterior lateral branch of right coronary artery. The patient underwent successful percutaneous transluminal coronary angioplasty with stent placement. Amphetamine abuse may play a role in acute myocardial infarction. Adverse cardiovascular manifestations of amphetamine can occur with sudden overt chest pain or present insidiously. In view of the potential association of amphetamine and myocardial infarction, physicians should not rely only upon clinical symptoms. This report highlights the diabetic patients with amphetamine abuse should undergo a routine electrocardiogram in such circumstances.

  12. Solar Activity, Different Geomagnetic Activity Levels and Acute Myocardial Infarction

    NASA Astrophysics Data System (ADS)

    Dimitrova, Svetla; Jordanova, Malina; Stoilova, Irina; Taseva, Tatiana; Maslarov, Dimitar

    Results on revealing a possible relationship between solar activity (SA) and geomagnetic activity (GMA) and acute myocardial infarction (AMI) morbidity are presented. Studies were based on medical data covering the period from 1.12.1995 to 31.12.2004 and concerned daily distribution of patients with AMI diagnose (in total 1192 cases) from Sofia region on the day of admission at the hospital. Analysis of variance (ANOVA) was applied to check the significance of GMA intensity effect and the type of geomagnetic storms, those caused by Magnetic Clouds (MC) and by High Speed Solar Wind Streams (HSSWS), on AMI morbidity. Relevant correlation coefficients were calculated. Results revealed statistically significant positive correlation between considered GMA indices and AMI. ANOVA revealed that AMI number was signifi- cantly increased from the day before (-1st) till the day after (+1st) geomagnetic storms with different intensities. Geomagnetic storms caused by MC were related to significant increase of AMI number in comparison with the storms caused by HSSWS. There was a trend for such different effects even on -1st and +1st day.

  13. Pharmacological postconditioning with lactic acid and hydrogen rich saline alleviates myocardial reperfusion injury in rats.

    PubMed

    Zhang, Guoming; Gao, Song; Li, Xiaoyan; Zhang, Lulu; Tan, Hong; Xu, Lin; Chen, Yaoyu; Geng, Yongjian; Lin, Yanliang; Aertker, Benjamin; Sun, Yuanyuan

    2015-04-30

    This study investigated whether pharmacological postconditioning with lactic acid and hydrogen rich saline can provide benefits similar to that of mechanical postconditioning. To our knowledge, this is the first therapeutic study to investigate the co-administration of lactic acid and hydrogen. SD rats were randomly divided into 6 groups: Sham, R/I, M-Post, Lac, Hyd, and Lac + Hyd. The left coronary artery was occluded for 45 min. Blood was withdrawn from the right atrium to measure pH. The rats were sacrificed at different time points to measure mitochondrial absorbance, infarct size, serum markers and apoptotic index. Rats in Lac + Hyd group had similar blood pH and ROS levels when compared to the M-Post group. Additionally, the infarct area was reduced to the same extent in Lac + Hyd and M-Post groups with a similar trends observed for serum markers of myocardial injury and apoptotic index. Although the level of P-ERK in Lac + Hyd group was lower, P-p38/JNK, TNFα, Caspase-8, mitochondrial absorbance and Cyt-c were all similar in Lac + Hyd and M-Post groups. The Lac and Hyd groups were able to partially mimic this protective role. These data suggested that pharmacological postconditioning with lactic acid and hydrogen rich saline nearly replicates the benefits of mechanical postconditioning.

  14. Thioredoxin-interacting protein and myocardial mitochondrial function in ischemia-reperfusion injury.

    PubMed

    Yoshioka, Jun; Lee, Richard T

    2014-02-01

    Cellular metabolism and reactive oxygen species (ROS) formation are interrelated processes in mitochondria and are implicated in a variety of human diseases including ischemic heart disease. During ischemia, mitochondrial respiration rates fall. Though seemingly paradoxical, reduced respiration has been observed to be cardioprotective due in part to reduced generation of ROS. Enhanced myocardial glucose uptake is considered beneficial for the myocardium under stress, as glucose is the primary substrate to support anaerobic metabolism. Thus, inhibition of mitochondrial respiration and uncoupling oxidative phosphorylation can protect the myocardium from irreversible ischemic damage. Growing evidence now positions the TXNIP/thioredoxin system at a nodal point linking pathways of antioxidant defense, cell survival, and energy metabolism. This emerging picture reveals TXNIP's function as a regulator of glucose homeostasis and may prove central to regulation of mitochondrial function during ischemia. In this review, we summarize how TXNIP and its binding partner thioredoxin act as regulators of mitochondrial metabolism. While the precise mechanism remains incompletely defined, the TXNIP-thioredoxin interaction has the potential to affect signaling that regulates mitochondrial bioenergetics and respiratory function with potential cardioprotection against ischemic injury.

  15. Consideration of QRS complex in addition to ST-segment abnormalities in the estimation of the "risk region" during acute anterior or inferior myocardial infarction.

    PubMed

    Vervaat, F E; Bouwmeester, S; van Hellemond, I E G; Wagner, G S; Gorgels, A P M

    2014-01-01

    The myocardial area at risk (MaR) is an important aspect in acute ST-elevation myocardial infarction (STEMI). It represents the myocardium at the onset of the STEMI that is ischemic and could become infarcted if no reperfusion occurs. The MaR, therefore, has clinical value because it gives an indication of the amount of myocardium that could potentially be salvaged by rapid reperfusion therapy. The most validated method for measuring the MaR is (99m)Tc-sestamibi SPECT, but this technique is not easily applied in the clinical setting. Another method that can be used for measuring the MaR is the standard ECG-based scoring system, Aldrich ST score, which is more easily applied. This ECG-based scoring system can be used to estimate the extent of acute ischemia for anterior or inferior left ventricular locations, by considering quantitative changes in the ST-segment. Deviations in the ST-segment baseline that occur following an acute coronary occlusion represent the ischemic changes in the transmurally ischemic myocardium. In most instances however, the ECG is not available at the very first moments of STEMI and as times passes the ischemic myocardium becomes necrotic with regression of the ST-segment deviation along with progressive changes of the QRS complex. Thus over the time course of the acute event, the Aldrich ST score would be expected to progressively underestimate the MaR, as was seen in studies with SPECT as gold standard; anterior STEMI (r=0.21, p=0.32) and inferior STEMI (r=0.17, p=0.36). Another standard ECG-based scoring system is the Selvester QRS score, which can be used to estimate the final infarct size by considering the quantitative changes in the QRS complex. Therefore, additional consideration of the Selvester QRS score in the acute phase could potentially provide the "component" of infarcted myocardium that is missing when the Aldrich ST score alone is used to determine the MaR in the acute phase, as was seen in studies with SPECT as gold

  16. Intravascular Ultrasound Observation of the Mechanism of No-Reflow Phenomenon in Acute Myocardial Infarction

    PubMed Central

    Li, Junxia; Wu, Longmei; Tian, Xinli; Zhang, Jian; Shi, Yujie

    2015-01-01

    Objective To study the mechanism of the no-reflow phenomenon using coronary angiography (CAG) and intravascular ultrasound (IVUS). Methods A total of 120 patients with acute myocardial infarction (AMI) who successfully underwent indwelling intracoronary stent placement by percutaneous coronary intervention (PCI). All patients underwent pre- and post-PCI CAG and pre-IVUS. No-reflow was defined as post-PCI thrombolysis in myocardial infarction (TIMI) grade 0, 1, or 2 flow in the absence of mechanical obstruction. Normal reflow was defined as TIMI grade 3 flow. The pre-operation reference vascular area, minimal luminal cross-sectional area, plaque cross-sectional area, lesion length, plaque volume and plaque traits were measured by IVUS. Results The no-reflow group was observed in 14 cases (11.6%) and normal blood-flow group in 106 cases (89.4%) based on CAG results. There was no statistically significant difference in the patients’ medical history, reference vascular area (no-flow vs. normal-flow; 15.5 ± 3.2 vs. 16.2 ± 3.3, p> 0.05) and lesion length (21.9 ± 5.1 vs. 19.5 ± 4.8, p> 0.05) between the two groups. No-reflow patients had a longer symptom onset to reperfusion time compared to normal blood-flow group [(6.6 ± 3.1) h vs (4.3 ± 2.7) h; p< 0.05] and higher incidence of TIMI flow grade< 3 (71.4% vs 49.0%, p< 0.05). By IVUS examination, the no-reflow group had a significantly increased coronary plaque area and plaque volume compared to normal blood-flow group [(13.7 ± 3.0) mm2 vs (10.2 ± 2.9) mm2; (285.4 ± 99.8) mm3 vs (189.7 ± 86.4) mm3; p< 0.01]. The presence of IVUS-detected soft plaque (57.1% vs. 24.0%, p< 0.01), eccentric plaque (64.2% vs. 33.7%, p< 0.05), plaque rupture (50.0% vs. 21.2%, p< 0.01), and thrombosis (42.8% vs. 15.3%) were significantly more common in no-reflow group. Conclusion There was no obvious relationship between the coronary risk factors and no-reflow phenomenon. The symptom onset to reperfusion time, TIMI flow grade before

  17. The effects of coronary angioplasty and reperfusion on myocardial flow distribution

    SciTech Connect

    Wahr, D.W.; Ports, T.A.; Botvinick, E.H.; Dae, M.; Schechtmann, N.; Hattner, R.S.; Turley, K.; Chiesa, N.A.

    1984-01-01

    To assess the effects of angioplasty (PTCA) and intracoronary streptokinase (STK) on relative myocardial perfusion, the authors administered Tc-99m macroaggregated albumin (MAA) into the uninvolved coronary artery (CA) before PTCA in 31 patients (PTS) and before STK in 8 PTS and In-111 MAA into the same vessel post intervention. In 8 PTCA PTS MAA was injected into the involved Ca. All STK and 36 PTCA studies were anatomically ''successful''. Computer processed images were acquired in registry and compared to each other, to 9 control studies, to angiography and to the distribution of T1-201 in rest images performed prior to or soon after intervention in 22 PTS. When MAA was injected into the uninvolved CA, scintigraphy revealed retraction of the perfusion zone from that of the involved CA in 15 of 28 successful PTCA PTS and in 4 of 8 STK PTS. When MAA was injected in the involved CA, a relative increase in perfusion was seen in 4 of 8 PTS post PTCA. There was no change in the perfusion pattern in controls or after unsuccessful PTCA. Compared to the distribution of T1-201, there was little change in global perfusion pattern. Regions previously supplied by collaterals (COLL) were generally well perfused after intervention. Only 2 STK and 5 PTCA PTS had angiographic collaterals. The authors conclude the following: 1) CA COLL perfusion may be inapparent angiographically; 2) CA COLL perfusion regresses rapidly after PTCA or STK; 3) Native perfusion is generally restored after successful PTCA or STK relieves the need for COLLS; and 4) Post intervention, total resting perfusion may not change, but its source may demonstrate beneficial alterations, shifting from COLL to native circulation.

  18. Effects of coronary angioplasty and reperfusion on distribution of myocardial flow

    SciTech Connect

    Wahr, D.W.; Ports, T.A.; Botvinick, E.H.; Dae, M.; Schechtmann, N.; Huberty, J.; Hattner, R.S.; O'Connell, J.W.; Turley, K.

    1985-08-01

    To assess the effects of angioplasty (PTCA) and intracoronary streptokinase (ICSK) on relative myocardial perfusion, the authors administered /sup 99m/Tc-macroaggregated albumin (MAA) to the uninvolved coronary artery before successful PTCA in 33 patients and before successful infusion of ICSK in eight patients and of /sup 111/In-MAA into the same vessel after the intervention. In 10 patients who underwent PTCA, MAA was injected into the involved, instrumented coronary artery. Computer-processed images were acquired in registry and compared. Similar scintigraphic studies were performed in six control patients and in 11 in whom planned interventions were not performed or were unsuccessful. Distribution of MAA was also compared with angiographic results and with the distribution of /sup 201/Tl on images obtained in patients at rest or on redistribution images obtained before and soon after intervention in 22 patients. In control patients and those studied after aborted or unsuccessful intervention, scintigraphic results showed excellent correlation with the angiographic anatomy and were without serial change. When MAA was injected into the uninvolved vessel, the scintigram revealed evidence of collateral perfusion with retraction of the perfusion zone from that of the involved coronary in 19 of 33 patients undergoing PTCA and in three of eight of those receiving ICSK. When MAA was injected into the involved artery, a relative increase in perfusion was seen in eight of 10 patients after PTCA. Although 30 patients demonstrated scintigraphic evidence of collateral vessels, only 10 patients had angiographic evidence of collateral circulation before intervention. The distribution of /sup 201/Tl demonstrated little change in its global pattern and regions previously supplied by collaterals were generally well perfused after intervention.

  19. Bovine Intestinal Alkaline Phosphatase Reduces Inflammation After Induction of Acute Myocardial Infarction in Mice

    PubMed Central

    Fiechter, Danielle; Kats, Suzanne; Brands, Ruud; van Middelaar, Ben; Pasterkamp, Gerard; de Kleijn, Dominique; Seinen, Willem

    2011-01-01

    Background There has been increasing evidence suggesting that lipopolysaccharide or endotoxin may be an important activator of the innate immune system after acute myocardial infarction. Bovine intestinal alkaline phosphatase reduces inflammation in several endotoxin mediated diseases by dephosphorylation of the lipid A moiety of lipopolysaccharide. The aim of this study was to investigate the effect of bovine intestinal alkaline phosphatase on reducing inflammation after acute myocardial infarction. Methods Just before permanent ligation of the left anterior descending coronary (LAD) artery to induce acute myocardial infarction in Balb/c mice, bovine intestinal alkaline phosphatase (bIAP) was administrated intravenously. After 4 hours, mice were sacrificed and the inflammatory response was assessed. Acute myocardial infarction induced the production of different cytokines, which were measured in blood. Results Treatment with bovine intestinal alkaline phosphatase resulted in a significant reduction of the pro-inflammatory cytokines IL-6, IL-1β and the chymase mouse mast cell protease-1. No difference in the production of the anti-inflammatory cytokine IL-10 was observed between the control group and the bovine intestinal alkaline phosphatase treated group. Conclusion In a mouse model of permanent LAD coronary artery ligation, bIAP diminishes the pro-inflammatory responses but does not have an effect on the anti-inflammatory response in the acute phase after acute myocardial infarction.

  20. Omega-3 Fatty Acids Do Not Protect Against Arrhythmias in Acute Nonreperfused Myocardial Infarction Despite Some Antiarrhythmic Effects.

    PubMed

    Mączewski, Michał; Duda, Monika; Marciszek, Mariusz; Kołodziejczyk, Joanna; Dobrzyń, Paweł; Dobrzyń, Agnieszka; Mackiewicz, Urszula

    2016-11-01

    Ventricular arrhythmias are an important cause of mortality in the acute myocardial infarction (MI). To elucidate the effect of the omega-3 polyunsaturated fatty acids (PUFAs) on ventricular arrhythmias in acute nonreperfused MI, rats were fed with normal or eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA)-enriched diet for 3 weeks. Subsequently the rats were subjected to either MI induction or sham operation. ECG was recorded for 6 h after the operation and episodes of ventricular tachycardia/fibrillation (VT/VF) were identified. Six hours after MI epicardial monophasic action potentials (MAPs) were recorded, cardiomyocyte Ca(2+) handling was assessed and expression of proteins involved in Ca(2+) turnover was studied separately in non-infarcted left ventricle wall and infarct borderzone. EPA and DHA had no effect on occurrence of post-MI ventricular arrhythmias or mortality. Nevertheless, DHA but not EPA prevented Ca(2+) overload in LV cardiomiocytes and improved rate of Ca(2+) transient decay, protecting PMCA and SERCA function. Moreover, both EPA and DHA prevented MI-induced hyperphosphorylation of ryanodine receptors (RyRs) as well as dispersion of action potential duration (APD) in the left ventricular wall. In conclusion, EPA and DHA have no antiarrhythmic effect in the non-reperfused myocardial infarction in the rat, although these omega-3 PUFAs and DHA in particular exhibit several potential antiarrhythmic effects at the subcellular and tissue level, that is, prevent MI-induced abnormalities in Ca(2+) handling and APD dispersion. In this context further studies are needed to see if these potential antiarrhythmic effects could be utilized in the clinical setting. J. Cell. Biochem. 117: 2570-2582, 2016. © 2016 Wiley Periodicals, Inc.

  1. Echocardiographic Predictors for Left Ventricular Remodeling after Acute ST Elevation Myocardial Infarction with Low Risk Group: Speckle Tracking Analysis

    PubMed Central

    Na, Hyun-Min; Lee, Joo Myung; Cha, Myung-Jin; Yoon, Yeonyee E.; Lee, Seung-Pyo; Kim, Hyung-Kwan; Kim, Yong-Jin; Sohn, Dae-Won

    2016-01-01

    Background We sought to assess echocardiographic predictors of left ventricular (LV) adverse remodeling after successfully reperfused acute ST elevation myocardial infarction (STEMI). LV remodeling is commonly found in STEMI patients and it may suggest adverse outcome in acute myocardial infarction. We sought to identify whether 2D strain and torsion be independent parameters for prediction of LV adverse remodeling. Methods We investigated 208 patients with low-risk STEMI patients who had follow up echocardiography at 6 or more months. After clinical assessments, all patients received revascularization according to current guideline. LV remodeling was defined as > 20% increase in end-diastolic volume (EDV) at follow up. Results During the follow-up (11.9 ± 5.3 months), 53 patients (25.5%) showed LV remodeling. In univariate analysis, EDV, end-systolic volume, deceleration time (DT), CK-MB, and global longitudinal strain (GLS) were associated with LV remodeling. In multivariate analysis, EDV [hazard ratio (HR): 0.922, 95% confidence interval (CI): 0.897–0.948, p< 0.001], GLS (HR: 0.842, 95% CI: 0.728–0.974, p = 0.020), DT (HR: 0.989, 95% CI: 0.980–0.998, p = 0.023) and CK-MB (HR: 1.003, 95% CI: 1.000–1.005, p = 0.033) independently predicted LV remodeling. However, global circumferential strain, net twist, and twist or untwist rate were not associated with remodeling. Conclusion Of various parameters of speckle strain, only GLS predicted adverse remodeling in STEMI patients. PMID:27358705

  2. Effect of Valproic Acid on Acute Lung Injury in a Rodent Model of Intestinal Ischemia Reperfusion

    PubMed Central

    Kim, Kyuseok; Li, Yongqing; Jin, Guang; Chong, Wei; Liu, Baoling; Lu, Jennifer; Lee, Kyoungbun; deMoya, Marc; Velmahos, George; Alam, Hasan B.

    2011-01-01

    Objectives Acute lung injury (ALI) is developed in many clinical situations and associated with significant morbidity and mortality. Valproic acid (VPA), a well-known anti-epileptic drug, has been shown to have anti-oxidant and anti-inflammatory effects in various ischemia/reperfusion (I/R) models. The purpose of this study was to investigate whether VPA could affect survival and development of ALI in a rat model of intestinal I/R. Methods Two experiments were performed. Experiment I: Male Sprague-Dawley rats (250–300 g) were subjected to intestinal ischemia (1 hour) and reperfusion (3 hours). They were randomized into 2 groups (n=7/group) 30 min after ischemia: Vehicle (Veh) and VPA (300 mg/kg, IV). Primary end-point for this study was survival over 4 hours from the start of ischemia. Experiment II: The histological and biochemical effects of VPA treatment on lungs were examined 3 hours (1 hr ischemia + 2 hrs reperfusion) after intestinal I/R injury (Veh vs. VPA, n = 9/group). An objective histological score was used to grade the degree of ALI. Enzyme linked immunosorbent assay (ELISA) was performed to measure serum levels of cytokine interleukins (IL-6 and 10), and lung tissue of cytokine-induced neutrophil chemoattractant (CINC) and myeloperoxidase (MPO). In addition, the activity of 8-isoprostane was analyzed for pulmonary oxidative damage. Results In Experiment I, four-hour survival rate was significantly higher in VPA treated animals compared to Veh animals (71.4% vs. 14.3%, p = 0.006). In Experiment II, ALI was apparent in all of the Veh group animals. Treatment with VPA prevented the development of ALI, with a reduction in the histological score (3.4 ± 0.3 vs. 5.3 ± 0.6, p = 0.025). Moreover, compared to the Veh control group the animals from the VPA group displayed decreased serum levels of IL-6 (952 ± 213 vs. 7709 ± 1990 pg/ml, p = 0.011), and lung tissue concentrations of CINC (1188 ± 28 vs. 1298 ± 27, p < 0.05), MPO activity (368 ± 23 vs. 490

  3. The influence of hypertonic mannitol on regional myocardial blood flow during acute and chronic myocardial ischemia in anesthetized and awake intact dogs.

    PubMed Central

    Willerson, J T; Watson, J T; Hutton, I; Fixler, D E; Curry, G C; Templeton, G H

    1975-01-01

    The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance was studied during acute myocardial ischemia in awake, unsedated and in anesthesized dogs and after myocardial infarction in awake unsedated dogs. Regional myocardial blood flow was measured with radioactive microspheres. Generalized increases in regional myocardial blood flow occurred after mannitol in all of the different animal models studied. The increases in coronary blood flow after mannitol were just as impressive in the nonischemic regions as in the ischemic portion of the left ventricle in all of the different models that were examined in this study. Improvement in regional myocardial blood flow to the ischemic area of the left ventricle after mannitol was associated with a reduction in ST segment elevation during acute myocardial ischemia in anesthetized dogs. The increases in regional myocardial flow after mannitol were also associated with increases in contractility, but the increases in flow appeared to be more impressive than the changes in contractility. The data obtained demonstrate that mannitol increases regional coronary blood flow to both ischemic and nonischemic myocardium in both anesthetized and awake, unsedated, intact dogs with acute and chronic myocardial ischemia and that mannitol reduces ST segment elevation during acute myocardial ischemia in anesthetized dogs. Thus the results suggest that under these circumstances the increases in regional myocardial blood flow after mannitol are of physiological importance in reducing the extent of myocardial injury. Since coronary blood flow increased to nonischemic regions the increases in regional myocardial flow demonstrated in this study after mannitol cannot be entirely explained by the mechanism of reduction in ischemic cell swelling. PMID:1123427

  4. Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs

    PubMed Central

    Stark, Christoffer K.-J.; Tarkia, Miikka; Kentala, Rasmus; Malmberg, Markus; Vähäsilta, Tommi; Savo, Matti; Hynninen, Ville-Veikko; Helenius, Mikko; Ruohonen, Saku; Jalkanen, Juho; Taimen, Pekka; Alastalo, Tero-Pekka; Saraste, Antti; Knuuti, Juhani; Savunen, Timo; Koskenvuo, Juha

    2016-01-01

    The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI. PMID:27199757

  5. Opening of the mitoKATP channel and decoupling of mitochondrial complex II and III contribute to the suppression of myocardial reperfusion hyperoxygenation.

    PubMed

    Liu, Bin; Zhu, Xuehai; Chen, Chwen-Lih; Hu, Keli; Swartz, Harold M; Chen, Yeong-Renn; He, Guanglong

    2010-04-01

    Diazoxide, a mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel opener, protects the heart from ischemia-reperfusion injury. Diazoxide also inhibits mitochondrial complex II-dependent respiration in addition to its preconditioning effect. However, there are no prior studies of the role of diazoxide on post-ischemic myocardial oxygenation. In the current study, we determined the effect of diazoxide on the suppression of post-ischemic myocardial tissue hyperoxygenation in vivo, superoxide (O(2)(-*)) generation in isolated mitochondria, and impairment of the interaction between complex II and complex III in purified mitochondrial proteins. It was observed that diazoxide totally suppressed the post-ischemic myocardial hyperoxygenation. With succinate but not glutamate/malate as the substrate, diazoxide significantly increased ubisemiquinone-dependent O(2)(-*) generation, which was not blocked by 5-HD and glibenclamide. Using a model system, the super complex of succinate-cytochrome c reductase (SCR) hosting complex II and complex III, we also observed that diazoxide impaired complex II and its interaction with complex III with no effect on complex III. UV-visible spectral analysis revealed that diazoxide decreased succinate-mediated ferricytochrome b reduction in SCR. In conclusion, our results demonstrated that diazoxide suppressed the in vivo post-ischemic myocardial hyperoxygenation through opening the mitoK(ATP) channel and ubisemiquinone-dependent O(2)(-*) generation via inhibiting mitochondrial complex II-dependent respiration.

  6. Inhibition of CD34+ cell migration by matrix metalloproteinase-2 during acute myocardial ischemia, counteracted by ischemic preconditioning

    PubMed Central

    Lukovic, Dominika; Zlabinger, Katrin; Gugerell, Alfred; Spannbauer, Andreas; Pavo, Noemi; Mandic, Ljubica; Weidenauer, Denise T.; Kastl, Stefan; Kaun, Christoph; Posa, Aniko; Sabdyusheva Litschauer, Inna; Winkler, Johannes; Gyöngyösi, Mariann

    2017-01-01

    Background. Mobilization of bone marrow-origin CD34+ cells was investigated 3 days (3d) after acute myocardial infarction (AMI) with/without ischemic preconditioning (IP) in relation to stromal-derived factor-1 (SDF-1α)/ chemokine receptor type 4 (CXCR4) axis, to search for possible mechanisms behind insufficient cardiac repair in the first days post-AMI.  Methods. Closed-chest reperfused AMI was performed by percutaneous balloon occlusion of the mid-left anterior descending (LAD) coronary artery for 90min, followed by reperfusion in pigs. Animals were randomized to receive either IP initiated by 3x5min cycles of re-occlusion/re-flow prior to AMI (n=6) or control AMI (n=12). Blood samples were collected at baseline, 3d post-AMI, and at 1-month follow-up to analyse chemokines and mobilized CD34+ cells. To investigate the effect of acute hypoxia, SDF-1α and matrix metalloproteinase (MMP)-2 in vitro were assessed, and a migration assay of CD34+ cells toward cardiomyocytes was performed.  Results. Reperfused AMI induced significant mobilisation of CD34+ cells (baseline: 260±75 vs. 3d: 668±180; P<0.001) and secretion of MMP-2 (baseline: 291.83±53.40 vs. 3d: 369.64±72.89; P=0.011) into plasma, without affecting the SDF-1α concentration. IP led to the inhibition of MMP-2 (IP: 165.67±47.99 vs. AMI: 369.64±72.89; P=0.004) 3d post-AMI, accompanied by increased release of SDF-1α (baseline: 23.80±12.36 vs. 3d: 45.29±11.31; P=0.05) and CXCR4 (baseline: 0.59±0.16 vs. 3d: 2.06±1.42; P=0.034), with a parallel higher level of mobilisation of CD34+ cells (IP: 881±126 vs. AMI: 668±180; P=0.026), compared to non-conditioned AMI. In vitro, CD34+ cell migration toward cardiomyocytes was enhanced by SDF-1α, which was completely abolished by 90min hypoxia and co-incubation with MMP-2.  Conclusions. Non-conditioned AMI induces MMP-2 release, hampering the ischemia-induced increase in SDF-1α and CXCR4 by cleaving the SDF-1α/CXCR4 axis, with diminished mobilization of

  7. Acute myocardial infarction caused by left atrial myxoma: Role of intracoronary catheter aspiration.

    PubMed

    Al-Fakhouri, Ahmad; Janjua, Muhammad; DeGregori, Michele

    2017-01-01

    Acute ST-segment elevation myocardial infarction (STEMI) caused by left atrial myxoma is very rare. Catheter-based approaches or thrombolytic therapy are mostly the first step in the management of STEMI with less time delay. We report a case of acute anterior/lateral STEMI caused by a left atrial myxoma. The patient was successfully treated by intracoronary aspiration with an Export aspiration catheter, with excellent distal coronary flow. Intracoronary catheter aspiration in acute myocardial infarction caused by a left atrial myxoma may help to salvage the infarcting myocardium with less time delay.

  8. CDP-choline prevents cardiac arrhythmias and lethality induced by short-term myocardial ischemia-reperfusion injury in the rat: involvement of central muscarinic cholinergic mechanisms.

    PubMed

    Yilmaz, M Sertac; Coskun, Cenk; Yalcin, Murat; Savci, Vahide

    2008-09-01

    In the present study, we aimed to determine whether cytidine-5'-diphosphatecholine (CDP-choline or citicoline) can improve the outcome of short-term myocardial ischemia-reperfusion injury in rats. Ischemia was produced in anesthetized rats by ligature of the left anterior descending coronary artery for 7 min followed by a reperfusion period of 7 min. Reperfusion-induced ventricular tachycardia (VT), ventricular fibrillation (VF), survival rate, and changes in arterial pressure were evaluated. Saline (1 ml/kg), CDP-choline (100, 250,and 500 mg/kg), or lidocaine (5 mg/kg) was intravenously injected in the middle of the ischemic period. Intracerebroventricular (i.c.v.) mecamylamine (50 microg) or atropine sulfate (10 microg) pretreatments were made 10 min before the coronary occlusion period. Pretreatment with intravenous (i.v.) atropine methylnitrate (2 and 5 mg/kg; i.v.) or bilateral vagotomy was performed 5 min before the induction of ischemia. An in vivo microdialysis study was performed in the nucleus ambiguus area (NA); choline and acetylcholine levels were measured in extracellular fluids. In control rats, VT, VF, and lethality were observed in 85%, 60% and 50% of the animals, respectively. Intravenous CDP-choline produced a short-term increase in blood pressure and reduced the incidence of VT, VF, and lethality dose-dependently when injected in the middle of the ischemic period. CDP-choline at doses of 250 and 500 mg/kg completely prevented death. Intracerebroventricular atropine sulfate pretreatment completely abolished the protective effect of CDP-choline, while mecamylamine pretreatment had no effect on the drug. CDP-choline increased the levels of extracellular choline and acetylcholine in the NA area. Bilateral vagotomy completely abolished the protective effect of CDP-choline in the reperfusion period. Moreover, the intravenous pretreatment with atropine methylnitrate produced dose-dependent blockade in the reduction of VT, VF, and mortality rates

  9. Assessment of myocardial injury after reperfusion with T1-201, Tc-99m pyrophosphate (PPi) and F-18 deoxyglucose (FDG)

    SciTech Connect

    Sochor, H.; Schwaiger, M.; Hansen, H.W.; Parodi, O.; Selin, C.; Huang, S.C.; Ellison, D.; Grover, M.; Schelbert, H.R.

    1984-01-01

    The authors previously demonstrated that enhanced glucose utilization assessed by FDG and Positron-CT in reperfused myocardium predicts functional recovery. This study compared segmental uptake of FDG with T1-201 and PPi as conventional indicators of tissue viability in 5 dogs, submitted to a 3 hr LAD occlusion followed by 24 hrs of reperfusion (R). Myocardial blood flow (MBF) was then determined by microspheres and T1-201, PPi and FDG administered i.v. Regional tracer concentrations were determined by well counting of tissue samples and grouped according to MBF (% of control). Severe flow reductions were associated with PPi uptake increase, T1-201 decrease and depressed glucose utilization representing mainly irreversible injury. Moderately reduced MBF areas showed the highest PPi uptake with T1-201 similar to MBF, but preserved FDG uptake not different from control, indicating partially viable tissue. Areas with MBF >60% had significantly increased PPi despite normal T1-201 uptake and enhanced glucose utilization and thus, preserved viability. Thus, assessment of tissue injury by conventional tracers such as T1-201 and PPi is limited. By contrast, quantification of residual glucose metabolism by PCT appears more accurate for evaluating myocardial viability and predicting potential functional recovery.

  10. Protective effect of mangiferin on myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats: role of AGE-RAGE/MAPK pathways

    PubMed Central

    Suchal, Kapil; Malik, Salma; Khan, Sana Irfan; Malhotra, Rajiv Kumar; Goyal, Sameer N.; Bhatia, Jagriti; Kumari, Santosh; Ojha, Shreesh; Arya, Dharamvir Singh

    2017-01-01

    Hyperglycemia induced advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) activation is thought to involve in the development of cardiovascular disease in diabetics. Activation of AGE-RAGE axis results in the oxidative stress and inflammation. Mangiferin is found in the bark of mango tree and is known to treat diseases owing to its various biological activities. Thus, this study was designed to evaluate the effect of mangiferin in ischemia-reperfusion (IR) induced myocardial injury in diabetic rats. A single injection of STZ (70 mg/kg; i.p.) was injected to male albino Wistar rats to induce diabetes. After confirmation of diabetes, rats were administered vehicle (2 ml/kg; i.p.) and mangiferin (40 mg/kg; i.p.) for 28 days. On 28th day, left anterior descending coronary artery was ligated for 45 min and then reperfused for 60 min. Mangiferin treatment significantly improved cardiac function, restored antioxidant status, reduced inflammation, apoptosis and maintained myocardial architecture. Furthermore, mangiferin significantly inhibited the activation of AGE-RAGE axis, c-Jun N-terminal kinase (JNK) and p38 and increased the expression of extracellular regulated kinase 1/2 (ERK1/2) in the myocardium. Thus, mangiferin attenuated IR injury in diabetic rats by modulation of AGE-RAGE/MAPK pathways which further prevented oxidative stress, inflammation and apoptosis in the myocardium. PMID:28181586

  11. Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction.

    PubMed

    Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

    2016-04-01

    Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI.From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses.The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina.Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy and drug

  12. Protective effect of moxonidine on ischemia/reperfusion-induced acute kidney injury through α2/imidazoline I1 receptor.

    PubMed

    Tsutsui, Hidenobu; Sugiura, Takahiro; Hayashi, Kentaro; Yukimura, Tokihito; Ohkita, Mamoru; Takaoka, Masanori; Matsumura, Yasuo

    2013-10-15

    Enhancement of renal sympathetic nerve activity during renal ischemia and norepinephrine overflow from the kidney after reperfusion play important roles in the development of ischemic acute kidney injury. Recently, we have found that moxonidine, an α2/imidazoline Ι1-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the excitation of renal sympathetic nervous system after reperfusion. In the present study, to clarify the renoprotective mechanisms of moxonidine (360 nmol/kg, i.v.) against ischemic acute kidney injury, we investigated the effect of intravenous (i.v.) and intracerebroventricular (i.c.v.) injection of efaroxan, an α2/Ι1 receptor antagonist, on the moxonidine-exhibited actions. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. The suppressive effect of moxonidine on enhanced renal sympathetic nerve activity during renal ischemia was not observed in the rat treated with either i.v. (360 nmol/kg) or i.c.v. (36 nmol/kg) of efaroxan. Furthermore, i.v. injection of efaroxan eliminated the preventive effect of moxonidine on ischemia/reperfusion-induced kidney injury and norepinephrine overflow, and i.c.v. injection of efaroxan did not completely inhibit the moxonidine's effects. These results indicate that moxonidine prevents the ischemic kidney injury by sympathoinhibitory effect probably via α2/Ι1 receptors in central nervous system and by suppressing the norepinephrine overflow through α2/Ι1 receptors on sympathetic nerve endings.

  13. Cardio-protective effects of combined l-arginine and insulin: Mechanism and therapeutic actions in myocardial ischemia-reperfusion injury.

    PubMed

    Venardos, Kylie M; Rajapakse, Niwanthi W; Williams, David; Hoe, Louise S; Peart, Jason N; Kaye, David M

    2015-12-15

    Reduced nitric oxide (NO) bioavailability plays a central role in the pathogenesis of myocardial ischemia-reperfusion injury (I-R), and reduced l-arginine transport via cationic amino acid transporter-1 is a key contributor to the reduced NO levels. Insulin can increase NO levels by increasing the transport of its substrate l-arginine but insulin alone exerts minimal cardiac protection in I-R. We hypothesized that combined insulin and l-arginine may provide cardioprotective effects in the setting of myocardial I-R. The effect of supplemental insulin, l-arginine and the combination was examined in cardiomyocytes exposed to hypoxia/reoxygenation and in isolated perfused mouse hearts undergoing ischemia/reperfusion. When compared to controls, cardiomyocytes treated upon reoxygenation with 1nM insulin+1mM l-arginine exhibited significant (all P<0.05) improvements in NO generation and mitochondrial membrane potential, with a concomitant fall in reactive oxygen species production and LDH release. Insulin also increased l-arginine uptake following hypoxia-reoxygenation (P<0.05; n=4-6). In langendorff perfused isolated mouse hearts, combined l-arginine-insulin treatment upon reperfusion significantly (all P<0.05; n=9-11) improved recovery of left ventricular developed pressure, rate pressure product and end diastolic pressure following ischemia, independent of any changes in post-ischemic coronary flow, together with significantly lower LDH release. The observed improvements were greater than l-arginine or insulin treatment alone. In isolated cardiomyocytes (n=3-5), 1nM insulin caused cationic amino acid transporter-1 to redistribute to the cellular membrane from the cytosol and the effects of insulin on l-arginine uptake were partially dependent on the PI3K/Akt pathway. l-arginine-insulin treatment may be a novel strategy to ameliorate I-R injury.

  14. Disseminated intravascular coagulation and acute myocardial necrosis caused by lightning.

    PubMed

    Ekoé, J M; Cunningham, M; Jaques, O; Balague, F; Baumann, R P; Humair, L; de Torrenté, A

    1985-01-01

    A 24-year-old woman was struck by lightning and suffered 20% second degree burns. She was admitted after cardiac and respiratory arrest. Despite intensive supportive care she died 24 h later of cardiogenic shock complicated by disseminated intravascular coagulation. At autopsy there was myocardial necrosis. Disseminated intravascular coagulation and myocardial necrosis are only rarely described as complications of lightning.

  15. Sevoflurane post-conditioning reduces rat myocardial ischemia reperfusion injury through an increase in NOS and a decrease in phopshorylated NHE1 levels.

    PubMed

    Cao, Jianfang; Xie, Hong; Sun, Ying; Zhu, Jiang; Ying, Ming; Qiao, Shigang; Shao, Qin; Wu, Haorong; Wang, Chen

    2015-12-01

    The protective effects of sevoflurane post-conditioning against myocardial ischemia/reperfusion (I/R) injury (MIRI) have been previously reported. However, the mechanisms responsible for these protective effects remain elusive. In this study, in order to investigate the molecular mechanisms responsible for the protective effects of sevoflurane post-conditioning on isolated rat hearts subjected to MIRI, Sprague-Dawley rat hearts were randomly divided into the following 6 groups: i) the sham-operated control; ii) 2.5% sevoflurane; iii) ischemia/reperfusion (I/R); iv) 2.5% sevoflurane post-conditioning plus I/R; v) 2.5% sevoflurane post-conditioning + NG-nitro-L-arginine methyl ester (L-NAME) plus I/R; and vi) L-NAME plus I/R. The infarct size was measured using 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Additionally, the myocardial nitric oxide (NO), NO synthase (NOS) and nicotinamide adenine dinucleotide (NAD+) levels were determined. Autophagosomes and apoptosomes in the myocardium were detected by transmission electron microscopy. The levels of Bcl-2, cleaved caspase-3, Beclin-1, microtubule-associated protein light chain 3 (LC3)‑I/II, Na+/H+ exchanger 1 (NHE1) and phosphorylated NHE1 protein were measured by western blot analysis. NHE1 mRNA levels were measured by reverse transcription-quantitative polymerase chain reaction. Compared with the I/R group, 15 min of exposure to 2.5% sevoflurane during early reperfusion significantly decreased the myocardial infarct size, the autophagic vacuole numbers, the NHE1 mRNA and protein expression of cleaved caspase-3, Beclin-1 and LC3-I/II. Post-conditioning with 2.5% sevoflurane also increased the NO and NOS levels and Bcl-2 protein expression (p<0.05 or p<0.01). Notably, the cardioprotective effects of sevoflurane were partly abolished by the NOS inhibitor, L-NAME. The findings of the present study suggest that sevoflurane post-conditioning protects the myocardium against I/R injury and reduces the myocardial

  16. Chronic melatonin consumption prevents obesity-related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet-induced obesity.

    PubMed

    Nduhirabandi, Frederic; Du Toit, Eugene F; Blackhurst, Dee; Marais, David; Lochner, Amanda

    2011-03-01

    Obesity, a major risk factor for ischemic heart disease, is associated with increased oxidative stress and reduced antioxidant status. Melatonin, a potent free radical scavenger and antioxidant, has powerful cardioprotective effects in lean animals but its efficacy in obesity is unknown. We investigated the effects of chronic melatonin administration on the development of the metabolic syndrome as well as ischemia-reperfusion injury in a rat model of diet-induced obesity (DIO). Male Wistar rats received a control diet, a control diet with melatonin, a high-calorie diet, or a high-calorie diet with melatonin (DM). Melatonin (4 mg/kg/day) was administered in the drinking water. After 16 wk, biometric and blood metabolic parameters were measured. Hearts were perfused ex vivo for the evaluation of myocardial function, infarct size (IFS) and biochemical changes [activation of PKB/Akt, ERK, p38 MAPK, AMPK, and glucose transporter (GLUT)-4 expression). The high-calorie diet caused increases in body weight (BW), visceral adiposity, serum insulin and triglycerides (TRIG), with no change in glucose levels. Melatonin treatment reduced the BW gain, visceral adiposity, blood TRIG, serum insulin, homeostatic model assessment index and thiobarbituric acid reactive substances in the DIO group. Melatonin reduced IFS in DIO and control groups and increased percentage recovery of functional performance of DIO hearts. During reperfusion, hearts from melatonin-treated rats had increased activation of PKB/Akt, ERK42/44 and reduced p38 MAPK activation. Chronic melatonin treatment prevente