High-dose Humanin analogue applied during ischemia exerts cardioprotection against ischemia/reperfusion injury by reducing mitochondrial dysfunction

摘要

AimAlthough the gold standard treatment for acute myocardial infarction is reperfusion therapy, reperfusion itself can cause myocardial damage via induction of cardiac mitochondrial dysfunction. This can lead to increased myocardial infarct size, arrhythmias, and left ventricular (LV) dysfunction. Recently, a newly discovered peptide, Humanin, has been shown to exert several beneficial effects including antioxidative and antiapoptosis effects. We recently reported that a Humanin analogue (HNG, 84g/kg) given prior to cardiac ischemia exerted cardioprotection against I/R injury, but failed to do so when it was given after ischemia was induced. However, in a clinical setting, patients can only be treated after the onset of ischemia. In this study, we investigated the potential benefit of various doses of HNG therapy (84, 168, 252g/kg) against myocardial I/R injury when applied during ischemia on cardiac arrhythmia, myocardial infarct size, cardiac mitochondrial function, and LV function.