Exercise and apelin have been shown to increase cardiac function and elicit tolerance to ischemia/reperfusion (IR) injuries. This study aimed at determining whether the combination of exercise training and apelin pretreatment could integrate the protective effects of each of them in the heart against IR injury. Male rats were divided into four experimental groups: 1: Rats with ischemia/reperfusion (IR), 2: subjected to exercise training for 8 weeks (EX+IR), 3: apelin-13 (10 nmol/kg/day) for 7 days (Apel+IR) in the last week of training, and 4: exercise training plus apelin-13 (EX+Apel+IR). Isolated hearts were perfused using the Langendorff method and subjected to 30 min of regional ischemia followed by 60 min of reperfusion. Treadmill exercise training was conducted for 8 weeks. Hemodynamic parameters were recorded throughout the experiment. Ischemiainduced arrhythmias, myocardial infarct size (IS), creatine kinase-MB (CK-MB) isoenzyme and plasma lactate dehydrogenase (LDH) activity was measured in all animals. Administration of apelin-13 plus exercise increased left ventricular developed pressure (LVDP) at the end of ischemia and reperfusion compared with other groups. After 30 min of ischemia, dP/dtmax was higher in EX+Apel+IR than in Apel+IR and EX+IR groups. During 30 min ischemia, exercise training, apelin-13 and combined treatment produced a significant reduction in the numbers of premature ventricular complexes. A combination of exercise and apelin-13 also reduced infarct size, CK-MB, LDH and severity of arrhythmia. These results suggest that combined therapies with apelin-13 and exercise training may integrate the beneficial effects of each of them alone on cardiac contractility, arrhythmia and limiting of infarct size. Level of evidence I; Therapeutic Studies -Investigating the Results of Treatment.
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