Cardioprotective effect of erythropoietin on sepsis-induced myocardial injury in rats

BACKGROUND: Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis. The cytoprotective function of erythropoietin (EPO) has been discovered and extensively studied. However, the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported. METHODS: The rat models of sepsis were produced by cecal ligation and perforation (CLP) surgery. Rats were randomly (random number) assigned to one of three groups (n=8 for each group): sham group, CLP group and EPO group (1000 IU/kg erythropoietin). Arterial blood was withdrawn at 3, 6, 12, and 24 hours after CLP. cTnI, BNP, CK-MB, LDH, AST, TNF-α, IL-6, IL-10, and CRP were tested by the ELISA assay. Changes of hemodynamic parameters were recorded at 3, 6, 12, 24 hours after the surgery. Histological diagnosis was made by hematoxylin and eosin. Flow cytometry was performed to examine cell apoptosis, myocardium mitochondrial inner membrane potential, and NF-κB (p65). Survival rate at 7 days after CLP was recorded. RESULTS: In the CLP group, myocardial enzyme index and inflammatory index increased at 3, 6, 12 and 24 hours after CLP compared with the sham group, and EPO significantly blocked the increase. Compared with the CLP group, EPO significantly improved LVSP, LV +dp/dt(max), LV −dp/dt(min), and decreased LVEDP at different time. EPO blocked the reduction of mitochondrial transmembrane potential, suppressed the cardiomyocyte apoptosis, inhibited the activation of NF-κB, and reduced the production of proinflmmatory cytokines. No difference in the survival rate at 7 days was observed between the CLP group and the EPO group. CONCLUSION: Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.