Protective effect of melanocortin peptides in rat myocardial ischemia

The influence of the melanocortin peptide ACTH-(1-24) (adrenocorticotropin) on the consequences of short-term coronary ischemia (5 min) followed by re perfusion, and the effect of the long-acting melanocortin [Nle(4),D-Phe(7)] alpha -melanocyte-stimulating hormone (NDP-MSH) on the damage induced by a permanent coronary occlusion, were investigated in anesthetized rats. Ische mia was produced by ligature of the left anterior descending coronary arter y. Reperfusion-induced arrhythmias [ventricular tachycardia (VT), ventricul ar fibrillation (VF)] and survival rate within the 5 min following reperfus ion, blood levels of free radicals detected 2 min after reperfusion by elec tron spin resonance spectrometry, and amount of healthy myocardial tissue, measured 72 h after permanent coronary occlusion on immunohistologically st ained serial sections, were evaluated. Postischemic reperfusion induced VT in all saline-treated rats, and VF and death in a high percentage of animal s (87%). In rats treated i.v. (2.5 min after coronary occlusion) with ACTH- (1-24) (0.16-0.48 mg/kg) there was a significantly dose-dependent reduction in the incidence of arrhythmias and lethality. Ischemia/reperfusion caused a large increase in free radical blood levels; treatment with ACTH-(1-24) (0.48 mg/kg i.v.) almost completely prevented this increase. In rats subjec ted to permanent coronary occlusion, the amount of healthy myocardial tissu e was much reduced in saline-treated rats, while in rats treated s.c. with NDP-MSH (0.27 mg/kg every 12 h) it was significantly higher. The present da ta demonstrate, for the first time, an unforeseen property of melanocortin peptides, i.e., their ability to significantly reduce both heart ischemia/r eperfusion injury and size of the ischemic area induced by permanent corona ry occlusion.