Erythropoietin enhances post-infarction ventricular functions after local intramyocardial delivery

Abstract

Objectives: Cardiovascular diseases are the most common causes of mortality and morbidity in the developed countries. More than just a promoter of erythropoiesis, Erythropoietin (EPO) has a much broader range of action on cardioprotective effects. We aimed to assess the functional improvement of EPO on both left and right ventricles in a rat myocardial infarction model. Methods: Adult male rats were divided into three groups as Sham, myocardial infarction treated with EPO (MI-EPO) and untreated MI control group (MI-C). Myocardial infarction was achieved by ligation of the LAD. MI-EPO group received four intramyocardial injections of Epoetin-α along the infarction border. Cardiac functions were investigated by pressure-volume (P-V) loop in both ventricles six weeks after the procedure. Infarction size and adverse effects of the treatment were evaluated by histological analysis. Results: Mortality was remarkably reduced with EPO treatment in the follow up period. Mean survival was 13 and 21 days in MI-C and MI-EPO groups, respectively. EPO treatment leads to significantly improved cardiac function. Left ventricular dp/dt max (baseline, 7374.84±1742.71mmHg/s vs. 5815.23±1257.10mmHg/s), ejection fraction (40,05±8,04 vs. 27,12±6,65), cardiac output (51331,77±16065,48 vs. 31083,60 ±15985,72) were enhanced and right ventricular pressure (23.08±4.10mmHg vs. 31.31±6.61mmHg) and end-systolic pressure (20,56±3,27 vs. 30,02±6,30) decreased. In the MI-EPO group infarction size was significantly smaller (27.8±3.4% vs. 20.1±2.8%) and intramural thrombosis was not observed in the myocardium. Conclusion: Our findings indicate directly intramyocardial administration of EPO has low adverse effect profile and improves cardiac functions in infarcted myocardium.