Abstract

Introduction: Acute myocardial infarction remains a leading cause of mortality. Rapid restoration of coronary blood flow is the cornerstone of treatment. Paradoxically, it leads to a condition known as ischemia/reperfusion (I/R) injury which precipitates more injuries to the heart. Erythropoietin (EPO), a hormone produced by the kidneys in response to cellular hypoxia, reportedly provides cardioprotection following cardiac I/R injury in many preclinical experiments. Unfortunately, clinical trials failed to demonstrate cardioprotection when EPO was given after reperfusion. Therefore, we aim to determine the temporal influences on administering EPO in cardiac I/R injury. Hypothesis: Administration of EPO at different time points provides varying efficacy in reducing arrhythmias, LV and cardiac mitochondrial dysfunction after cardiac I/R injury. Methods: Male Wistar rats were divided into sham-operated and cardiac I/R group. In I/R group, rats were subdivided into 4 groups (n=10/group): vehicle, EPO pretreatment (P-EPO), EPO given during ischemia (I-EPO), and EPO given at reperfusion onset (R-EPO). EPO was intravenously given to the rats (5000 unit/kg). Rats underwent 30-min LAD ligation followed by 120-min reperfusion. Arrhythmia scores and LV function were recorded throughout the protocol. Then, rats were sacrificed to determine infarct size and mitochondrial function. Results: Cardiac I/R injury induced arrhythmias, LV and mitochondrial dysfunction (Fig . Administration of EPO before or during ischemia, but not at the onset of reperfusion, significantly attenuated LV dysfunction and infarct size. However, EPO did not reduce arrhythmia scores. Although EPO given at all time points reduced mitochondrial reactive oxygen species, EPO given at reperfusion failed to prevent mitochondrial swelling (Fig) . Conclusions: Acute EPO treatment before or during ischemia, but not at the onset of reperfusion, exerted cardioprotection against I/R injury.

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