Serum Levels Of Cardiac troponin-I Research Articles

The effect of bempedoic acid an ATP-citrate lyase inhibitor on cardiovascular risk factors in rats with experimentally induced myocardial infarction and hyperlipidemia.

Control of hyperlipidemia is believed to reduce major cardiovascular events such as cardiovascular death, myocardial infarction, nonfatal stroke, hospitalization for unstable angina, and coronary revascularization. The benefits of monotherapy with Bempedoic acid (BA) as a hypolipidemic agent given after induction of myocardial infarction (MI) in reducing the risk of acute MI worth being investigated, therefore this study was designed to investigate the effectiveness of Bempedoic acid on reducing cardiovascular risk factors in rats with induced hyperlipidemia and myocardial infarction compared to Rosuvastatin. Male albino rats (n=40) were divided into five equal groups, each with eight rats, the first group served as a negative control group, the second group (diet-induced hyperlipidemia and Isoprenaline induced myocardial infarction) served as a positive control group, the third group (diet-induced hyperlipidemia and Isoprenaline induced myocardial infarction) received daily oral administration of Rosuvastatin for 12 weeks, the fourth group (diet-induced hyperlipidemia, DIH) received Bempedoic acid for 4 weeks as prophylaxis and then myocardial infarction was induced and Bempedoic acid administration was continued for the remaining 8 weeks, and the fifth group (diet-induced hyperlipidemia and Isoprenaline induced myocardial infarction) received a daily oral administration of Bempedoic acid for 12 weeks as a treatment. After 12 weeks, blood samples were withdrawn by cardiac puncture for measuring and evaluating lipid profiles and other parameters. Bempedoic acid and Rosuvastatin significantly reduce mean serum levels of lipid profiles; Total cholesterol, LDL and triglyceride, increase HDL and reduce cardiac enzyme levels as compared with the positive control group. The findings from this study suggested that Bempedoic acid as monotherapy either as a therapy or as prophylaxis was effective in reducing lipid parameters, LDL, Tch, and TG and cardiac enzymes creatine kinase-MB (CK-MB) and serum level of cardiac troponin-I (cTn-I) compared with the positive control group and was not superior to Rosuvastatin in these parameters but taking BA as prophylaxis could prevent the morbidity with cardiovascular events as it was effective in reducing the above parameters by greater percentages than BA and Rosuvastatin therapy.. Both drugs showed similar profiles in blood pressure and heart rate measurements.

Potential Use of Quercetin as Protective Agent against Hydroxychloroquine Induced Cardiotoxicity

The aim of this study is to investigate the protective effects of Quercetin (QCT) on Hydroxychloquine (HCQ)-induced myocardial affection in rats. HCQ has been found to produce toxic effects including cardiac manifestation. Adding QCT to HCQ ameliorates its effects and prevents cardiac manifestations. For this purpose, eighty adult male rats were divided into four groups (n = 20). Group 1 (control) and group 2 (QCT-treated). Group 3 (HCQ treated) received 20 mg/kg of HCQ and group 4 (QCT + HCQ treated) received quercetin (50 mg/kg; orally) combined with HCQ for 4 weeks. Cardiac troponin-I and oxidative markers (Malondialdehyde (MDA), and total serum antioxidant) were estimated in serum. In addition, histopathological and morphometric changes of the rat heart were assessed. The HCQ treated group showed increased serum levels of cardiac troponin-I, MDA and decreased serum levels of total antioxidant. Pathological picture of myocardial hypertrophy and degeneration together with depleted cardiac tissue expression of troponin T were also observed. The characteristic features were presence of whorled myelin bodies and curvilinear bodies by EM examination. These parameters improved better in the group receiving combination of QCT together with HCQ. So, Adding QCT to HCQ could be prophylactic measure against its cardiotoxic effect compared with HCQ treatment alone.

Evaluation of Cardiac Troponin Level Following Generalized Tonic-Clonic Seizure in Children; Cross-sectional Study

Background: Cardiac troponin I (CTnI) is recognized as a proper marker for early detection of cardiac damage. Generalized tonic-clonic (GTC) seizures may lead to cardiac ischemia or myocardial injury associated with elevated CTnI. The present study aimed at evaluating the level of CTnI in children with status GTC seizures. Methods: 50 patients with GTC seizures and a normal cardiac function referred to Amirkabir Hospital, Arak, Iran were evaluated. The medical history of all patients was taken, and clinical examinations were performed. For all patients were performed Serum CTnI measurements, electroencephalography (EEG), electrocardiography (ECG), and echocardiography. Results: The patients’ mean age was 7.80 ± 4.01 years and 26 (52%) children were female (female: male ratio, 1.08). the mean duration of seizure was 31.54 ± 1.56 minutes. Abnormal EEG patterns were documented in 83 (86%) patients, while abnormal CT scan was not found in any of the patients. The mean level of CTnI was at the high end of the range in patients (57.02 ± 10.80 ng/mL). There was a positive correlation between serum CTnI and age (P = 0.001, R = 0.492). Also, the serum level of CTnI was significantly correlated with the onset of GTC seizure (R = 0.004, P = 0.001). Conclusion: The serum CTnI level exceeded the normal level in children with seizures. Therefore, cardiac monitoring of patients with status GTC seizures may be helpful in the ictal and postictal phases for evaluating cardiac injury, especially in children with risk factors for coronary diseases, such as Kawasaki disease, cardiomyopathy, or coronary anomalies.

Human amniotic membrane mesenchymal stem cells-conditioned medium attenuates myocardial ischemia-reperfusion injury in rats by targeting oxidative stress.

Objective(s):Ischemic heart diseases (IHD) are one of the major causes of death worldwide. Studies have shown that mesenchymal stem cells can secrete and release conditioned medium (CM) which has biological activities and can repair tissue injury. This study aimed to investigate the effects of human amniotic membrane mesenchymal stem cells (hAMCs)-CM on myocardial ischemia/reperfusion (I/R) injury in rats by targeting oxidative stress. Materials and Methods:Male Wistar rats (40 rats, weighing 200–250 g) were randomly divided into four groups: Sham, myocardial infarction (MI), MI + culture media, and MI + conditioned medium. MI was induced by ligation of the left anterior descending coronary artery for 30 min. After 15 min of reperfusion, intramyocardial injections of hAMCs-CM or culture media (150 μl) were performed. At the end of the experiment, serum levels of cardiac troponin-I (cTn-I), myocardial levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as cardiac histological changes were evaluated.Results:HAMCs-CM significantly decreased cTn-I and MDA levels and increased SOD and GPx activities (P<0.05). In addition, hAMCs-CM improved cardiac histological changes and decreased myocardial injury percentage (P<0.05). Conclusion:This study showed that hAMCs-CM has cardioprotective effects in the I/R injury condition. Reduction of oxidative stress by hAMCs-CM plays a significant role in this context. Based on the results of this study, it can be concluded that hAMCs-CM can be offered as a therapeutic candidate for I/R injury in the future, but more research is needed.

Up-Regulation of Cell-Free MicroRNA-1 and MicroRNA-221-3p Levels in Patients with Myocardial Infarction Undergoing Coronary Angiography.

Purpose: Myocardial infarction (MI), known as a multifactorial disease, remains the predominant cause of mortality and sudden deaths annually. The current study aimed to measure the expression of microRNA-1 and microRNA-221-3p in MI patients. Methods: In the current study, 100 healthy controls (with no history of heart disease) and 200 patients with MI were selected. Patients were divided into two groups based on angiography results: normal (no significant artery stenosis) and primary percutaneous coronary intervention (primary PCI, significant artery stenosis). The levels of microRNA-1 and microRNA-221-3p were quantified using real-time quantitative polymerase chain reaction. The correlation between levels of microRNAs and the common cardiac markers were analyzed statistically. Results: In comparison to fold change, microRNA-1 elevations were 8.5-fold in normal patients and 60-fold in patients with primary PCI; while microRNA-221-3p levels were 210- fold higher in primary PCI and 31.31-fold higher in normal cases compared with the healthy controls. Receiver operating characteristic analysis showed that the area under the curve (AUC) for circulating microRNA-1 and microRNA-221 were 0.903 and 0.958 in normal patients and 0.927 and 0.985 in primary PCI patients (p < 0.0001), respectively. Pearson correlation (ρ) analysis showed that circulation of microRNA-1 correlated with serum levels of cardiac troponin I (CTnI) (ρ =0.24), creatinine (ρ =0.34), creatinine kinase-myocardial band (CK-MB) (ρ =0.31), and microRNA-221-3p was significantly correlated with serum levels of CTnI (ρ =0.6), creatinine (ρ =0.41), and CK-MB (ρ =0.37), (P < 0.0001). Conclusion: The study underscored the potential of microRNA-1 and microRNA-221-3p as informative biomarkers and positively correlated with artery stenosis in MI.

Application of Dexmedetomidine in Cardiopulmonary Bypass Prefilling.

Objective:The purpose of this study was to explore the application of dexmedetomidine (Dex) in cardiopulmonary bypass.Methods:A total of 60 patients undergoing elective cardiopulmonary bypass were divided into control (C) group and Dex group. In the Dex group, appropriate amount of Dex was added into the membrane lung prefilling solution before anesthesia induction, while those in control group were given normal saline. The levels of mean arterial pressure (MAP) and heart rate (HR) at different times were measured. The levels of cardiac troponin I (CTNI), malondialdehyde (MDA), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) at different points (T0/T1/T2/T3/T4) in both groups were measured by enzyme-linked immunosorbent assay kits.Results:The intraoperative and postoperative levels of MAP and HR in the 2 groups were significantly lower than those preoperatively (P < .05). The levels of MAP and HR in the Dex group were significantly lower than those of the C group (P < .05). The levels of CTNI/MDA/IL-6/TNF-α at different points in both groups were significantly higher than those at T0 (P < .05). The serum levels of CTNI, MDA, IL-6, and TNF-α in the Dex group at T1/T2/T3/T4 were significantly lower than those in the C group (P < .05). The rate of arrhythmia in the Dex group was significantly lower than that in the C group (P < .05).Conclusion:Dexmedetomidine has a stable effect in cardiopulmonary priming solution.

Severity and properties of cardiac damage caused by Streptococcus pneumoniae are strain dependent.

Streptococcus pneumoniae is an opportunistic Gram-positive pathogen that can cause invasive disease. Recent studies have shown that S. pneumoniae is able to invade the myocardium and kill cardiomyocytes, with one-in-five adults hospitalized for pneumococcal pneumonia having a pneumonia-associated adverse cardiac event. Furthermore, clinical reports have shown up to a 10-year increased risk of adverse cardiac events in patients formerly hospitalized for pneumococcal bacteremia. In this study, we investigated the ability of nine S. pneumoniae clinical isolates, representing eight unique serotypes, to cause cardiac damage in a mouse model of invasive disease. Following intraperitoneal challenge of C57BL/6 mice, four of these strains (D39, WU2, TIGR4, and 6A-10) caused high-grade bacteremia, while CDC7F:2617–97 and AMQ16 caused mid- and low-grade bacteremia, respectively. Three strains did not cause any discernible disease. Of note, only the strains capable of high-grade bacteremia caused cardiac damage, as inferred by serum levels of cardiac troponin-I. This link between bacteremia and heart damage was further corroborated by Hematoxylin & Eosin and Trichrome staining which showed cardiac cytotoxicity only in D39, WU2, TIGR4, and 6A-10 infected mice. Finally, hearts infected with these strains showed varying histopathological characteristics, such as differential lesion formation and myocytolysis, suggesting that the mechanism of heart damage varied between strains.

Evaluation of cardiopulmonary and inflammatory markers in dogs with heartworm infection treated using the slow kill method

This study evaluated the changes in the levels of cardiac, hemostatic, and inflammatory biomarkers in 12 dogs with different severities of heartworm infection treated using the slow kill protocol, consisting of 6–10μg/kg of ivermectin and 10mg/kg of doxycycline combination. The serum levels of cardiac troponin-I, D-dimer, C-reactive protein, and interleukin-6 were measured on the day of diagnosis (D0), after termination of doxycycline administration (D30), after termination of the slow kill treatment (D180), and 10 months after the initiation of therapy (D300). Heartworm antigenemia was cleared in 4/4 class I dogs, 3/4 class II dogs, and 1/4 class III dogs at the end of the therapy (D180), and in 4/4 class I, 4/4 class II, and 1/4 class III dogs at the end of the study (D300). The serum levels of the markers in class I dogs on the day of diagnosis (D0) were within the reference range, while the levels in class II and III dogs were above the reference range. Further, the serum levels of the markers in all dogs decreased significantly at the end of the study (D300), although some markers in class III dogs remained at pathological levels. This study revealed that the slow kill method should be used only as an alternative therapeutic protocol for dogs with low worm burden (class I and II). As the slow kill method alone may not effectively reduce all pathological changes in dogs with heavy worm burden and severe clinical signs (class III), adjuvant therapies including steroids and anti-thromboembolics should be used to minimize the risk of complications.

The Possible Cardio-Reno- Protective Effects of Vanillin on Isopretrenol- Induced Myocardial Infarction in Rats

Myocardial infarction (MI) continues to be a major public health problem in the world. Vanillin is a natural phenolic compound that possesses significant anti-oxidant and anti-inflammatory activities. The present study aimed to investigate the effects of pretreatment with vanillin (150 mg/kg, p.o.) and vanillin (300 mg/kg, p.o.) on isoprenaline-induced MI in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), in addition to serum level of cardiac troponin-I (cTn-I), as well as antioxidant activity of cardiac catalase (CAT) as well as cardiac contents of RGH, lipid peroxides, and nitrite. Furthermore Electrocardiograph (ECG) monitoring and histological examinations of cardiac tissues were done. In addition markers chosen to assess renal impairment included serum and urine levels of creatinin, blood urea nitrogen (BUN), also creatinine clearance (Ccr), urea clearance (Ucr) and glomerular filteration rate (GFR) were assessed. In addition, antioxidant activity of renal CAT and renal contents of RGH, lipid peroxides, and nitrite. Furthermore, histological examinations of renal tissues were done. Isoprenaline increased serum CK-MB and LDH activity and cTn-I level, cardiac and renal oxidative stress biomarkers. In addition, it produced ST-segment elevation and degenerative changes in heart and renal tissues. Pretreatment with vanillin in previous doses significantly suppressed isoprenaline-induced pathological changes, as the elevated levels of cTn-I, LDH and CK-MB in serum coupled with reduction in cardiac and renal oxidative stress markers. Moreover marked improvement in ECG and histopathologic alterations in both cardiac and renal tissues were produced. In conclusion, vanillin can be regarded as a promising cardio- and reno- protective natural agent in MI.

Determination of the serum levels of troponin I and creatinine among Sudanese type 2 diabetes mellitus patients.

Background:Diabetes mellitus (DM) is a significant risk factor for developing cardiac diseases. Hence, we compare the serum levels of cardiac troponin I (CTnI) among type 2 diabetic and healthy patients. We additionally correlated CTnI and creatinine levels with duration of disease.Materials and Methods:A cross-sectional study was conducted at Department of Clinical Chemistry, Sudan University of Sciences and Technology, Khartoum, Sudan, from February 2008 to February 2011. 200 patients diagnosed with DM type 2 from Jabir Abulizz Diabetes Centre in Khartoum state, Sudan, and 100 healthy volunteers were included in this study. Blood samples were collected from both groups, and the serum levels of CTnI, creatinine, fasting plasma glucose and glycosylated hemoglobin (HbA1c) levels were measured.Results:Significant increase in serum levels of CTnI, glucose, HbA1c, and creatinine was observed in diabetic patients compared to healthy controls. In addition, the significant increase in CTnI and creatinine levels was observed among diabetic patients with ischemic heart disease or hypertension when compared with those without ischemic heart disease or hypertension. Further a strong positive correlation was observed between the duration of diabetes and the serum levels of CTnI and creatinine (r = 0.84, P > 0.01) and (r = 0.72, P > 0.01), respectively.Conclusion:The higher levels of CTnI and creatinine may be indicative of progressive cardiovascular disease and nephropathy among diabetic patients.

Trastuzumab Alters the Expression of Genes Essential for Cardiac Function and Induces Ultrastructural Changes of Cardiomyocytes in Mice

Treatment with trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), very successfully improves outcomes for women with HER2-positive breast cancer. However, trastuzumab treatment was recently linked to potentially irreversible serious cardiotoxicity, the mechanisms of which are largely elusive. This study reports that trastuzumab significantly alters the expression of myocardial genes essential for DNA repair, cardiac and mitochondrial functions, which is associated with impaired left ventricular performance in mice coupled with significant ultrastructural alterations in cardiomyocytes revealed by electron microscopy. Furthermore, trastuzumab treatment also promotes oxidative stress and apoptosis in myocardium of mice, and elevates serum levels of cardiac troponin-I (cTnI) and cardiac myosin light chain-1 (cMLC1). The elevated serum levels of cMLC1 in mice treated with trastuzumab highlights the potential that cMLC1 could be a useful biomarker for trastuzumab-induced cardiotoxicity.

Protective effects of atorvastatin and quercetin on isoprenaline-induced myocardial infarction in rats

Myocardial infarction (MI) continues to be a major public health problem in the world. Statins exhibit cardio-protective effects by several mechanisms beyond their lipid lowering activity. Quercetin is a natural flavonoid that possesses significant anti-oxidant and antiinflammatory activities. The present study aimed to investigate the effects of pretreatment with atorvastatin (10mg/kg) and quercetin (50mg/kg), as well as their combination on isoprenaline-induced MI in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB) and serum level of cardiac troponin-I (cTn-I), as well as oxidative stress and inflammatory biomarkers including serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) as well as cardiac contents of lipid peroxides, reduced glutathione (GSH), and nitrite. Furthermore, ECG monitoring and histological examinations of cardiac tissues were done. Isoprenaline increased serum CK-MB activity and cTn-I level as well as inflammatory and oxidative stress biomarkers. In addition, it produced ST-segment elevation and degenerative changes in heart tissues. Pretreatment with atorvastatin suppressed significantly the elevated levels of cTn-I, CRP, TNF-α, and IL-10 in serum coupled with reduction in cardiac lipid peroxides; however, it increased cardiac nitrite content. Quercetin decreased isoprenaline-induced changes in oxidative stress and inflammatory biomarkers with marked improvement in ECG and histopathologic alterations. Combination of quercetin with atorvastatin resulted in similar protective effects. In conclusion, quercetin can be regarded as a promising cardio-protective natural agent in MI alone or combined with atorvastatin.

Propofol has delayed myocardial protective effects after a regional ischemia/reperfusion injury in an in vivo rat heart model

BackgroundIt is well known that propofol protects myocardium against myocardial ischemia/reperfusion injury in the rat heart model. The aim of this study was to investigate whether propofol provides a protective effect against a regional myocardial ischemia/reperfusion injury in an in vivo rat heart model after 48 h of reperfusion.MethodsRats were subjected to 25 min of left coronary artery occlusion followed by 48 h of reperfusion. The sham group received profopol without ischemic injury. The control group received normal saline with ischemia/reperfusion injury. The propofol group received profopol with ischemia/reperfusion injury. The intralipid group received intralipid with ischemia/reperfusion injury. A microcatheter was advanced into the left ventricle and the hemodynamic function was evaluated. The infarct size was determined by triphenyltetrazolium staining. The serum level of cardiac troponin-I (cTn-I) was determined by ELISA (enzyme-linked immunosorbent assay).ResultsPropofol demonstrated protective effects on hemodynamic function and infarct size reduction. In the propofol group, the +dP/dtmax (P = 0.002) was significantly improved compared to the control group. The infarct size was 49.8% of the area at risk in the control group, and was reduced markedly by administration of propofol to 32.6% in the propofol group (P = 0.014). The ischemia/reperfusion-induced serum level of cTn-I was reduced by propofol infusion during the peri-ischemic period (P = 0.0001).ConclusionsPropofol, which infused at clinically relevant concentration during the peri-ischemic period, has delayed myocardial protective effect after regional myocardial ischemia/reperfusion injury in an in vivo rat heart model after 48 h of reperfusion.

Dose remifentanil have a myocardial protective effect against a regional ischemia-reperfusion injury in an in vivo rat heart model?.

It is known that some opioids protect the myocardial tissue from myocardial ischemia-reperfusion (I/R) injury. The aim of this study was to investigate whether remifentanil, at a clinically relevant concentration that's during the peri-ischemic period, has a protective effect against a regional I/R injury in an in vivo rat heart model. Rats were subjected to 25 minutes of coronary artery occlusion and this was followed by 24 hours of reperfusion. A microcatheter was advanced into the left ventricle and the hemodynamic function was evaluated after 24 hours of reperfusion. The infarct size was determined by triphenyltetrazolium staining. The serum level of cardiac troponin-I (cTnI) was determined by ELISA (enzyme-linked immunosorbent assay). Remifentanil administration during the peri-ischemic period didn't show any identifiable protective effects for the hemodynamic function or to reduce the infarct size. In the control group, the peak rate of the ventricular pressure increase (+dP/dt(max)) (P < 0.05) and the peak rate of the intraventricular pressure decline (-dP/dt(max) P < 0.05) were significantly decreased as compared to those values for the sham group. In the remifentanil group, the +dP/dt(max) and -dP/dt(max) were not improved compared to those values of the control group. The infarct size was 45.6% of the area at risk in the control group, and the infarct size was reduced by administration of remifentanil to 43.2% in the remifentanil group. The I/R-induced serum level of cTn-I was not reduced by remifentanil infusion during the peri-ischemic period. Remifentanil, at a clinically relevant concentration that's infused during the peri-ischemic period, has no myocardial protective effect after regional myocardial I/R injury in an in vivo rat heart model.

In Vivo Activation of Peroxisome Proliferator-Activated Receptor-δ Protects the Heart from Ischemia/Reperfusion Injury in Zucker Fatty Rats

Peroxisome proliferator-activated receptor (PPAR)-delta is a transcription factor that belongs to the PPAR family. PPAR-delta is abundantly expressed in the heart, and its role in the heart is largely unknown. We tested whether pharmacological activation of PPAR-delta protects the heart from ischemia/reperfusion (I/R) injury in male Zucker fatty rats, a rodent model of obesity and dyslipidemia. A highly selective PPAR-delta agonist, [4-[[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl] thio]-2-methylphenoxy]acetic acid (GW0742), was administered for 7 days at 10 mg/kg/day (p.o., once a day). Ischemic injury was produced by occlusion of the left anterior descending artery for 30 min followed by reperfusion for up to 24 h. Treatment with GW0742 reduced serum levels of cardiac troponin-I and infarct size by 63% (p < 0.01) and 32% (p < 0.01), respectively, and improved left ventricular function. Treatment with GW0742 up-regulated gene expression involved in cardiac fatty acid oxidation, increased fat use in the heart, and reduced serum levels of free fatty acids. The enhanced cardiac expression of interleukin (IL)-6, IL-8, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 induced by I/R were significantly attenuated by GW0742. Treatment with GW0742 also reduced apoptotic cardiomyocytes by 34% and cardiac caspase-3 activity by 61% (both p < 0.01 versus vehicle). GW0742 differentially regulated Bcl family members, favoring cell survival, and attenuated I/R-induced cardiac mitochondrial damage. In addition, GW0742 treatment augmented the cardiac Akt signaling pathway, as reflected by enhanced phospho-3-phosphoinositide-dependent kinase-1 and p-Akt. The results indicate that activation of PPAR-delta protected the heart from I/R injury in Zucker fatty rats, and multiple mechanisms including amelioration of lipotoxicity, anti-inflammation, and up-regulation of prosurvival signaling contribute together to the cardioprotection.

Medroxyprogesterone Acetate Prevents the Cardioprotective Effects of 17β‐estradiol

Many studies have shown protective effects of estrogen administration in models of cardiovascular disease. However, there is a discrepancy between these data and those of the recent clinical trials with hormone replacement. One possible explanation for the divergent data is the addition of progestin to the hormone regimen in both the WHI and HERS trials. The aim of the current study was to determine the effects of a combination of 17β-estradiol (E2; 20μg) and medroxyprogesterone acetate (MPA; 80μg) on infarct size. Anesthetized male rabbits were administered vehicle, E2, or a combination of E2/MPA intravenously 30 minutes before a 30-minute occlusion of the coronary artery and 4 hours of reperfusion. Administration of E2 30 minutes before induction of myocardial ischemia significantly reduced infarct size as a percent of the area of risk (21.7 + 5.2; P < 0.001) compared to vehicle (56.1 + 3.4). However, when combined with MPA, E2 failed to elicit a protective effect on infarct size (49.2 + 5.2). Treatment with E2 reduced serum levels of cardiac troponin-I, immune complex deposition in myocardial tissue, and activation of the complement system. All of these effects were reversed by MPA. The results suggest that MPA antagonizes the infarct-sparing effects of E2, possibly through modulation of the immune response after ischemia and reperfusion. Funding: Cardiovascular Research Fund, University of Michigan Medical School