Vol. 297, Issue 3, 1082-1087, June 2001

Protective Effect of Melanocortin Peptides in Rat Myocardial Ischemia

Carla Bazzani, Salvatore Guarini, Annibale R. Botticelli, Davide Zaffe, Aldo Tomasi, Anna Bini , Maria Michela Cainazzo, Giuseppe Ferrazza, Chiara Mioni and Alfio Bertolini

Department of Biomedical Sciences, Section of Pharmacology (C.B., S.G., M.M.C., G.F., C.M., A.B.) and Section of General Pathology (A.T., A.B.), University of Modena and Reggio Emilia, Modena, Italy; Department of Morphological Sciences and Forensic Medicine, University of Modena and Reggio Emilia, Modena, Italy (D.Z.); and Department of Human Pathology, University of Pavia, Pavia, Italy (A.R.B)

The influence of the melanocortin peptide ACTH-(1-24) (adrenocorticotropin) on the consequences of short-term coronary ischemia (5 min) followed by reperfusion, and the effect of the long-acting melanocortin [Nle⁴,D-Phe⁷]-melanocyte-stimulating hormone (NDP-MSH) on the damage induced by a permanent coronary occlusion, were investigated in anesthetized rats. Ischemia was produced by ligature of the left anterior descending coronary artery. Reperfusion-induced arrhythmias [ventricular tachycardia (VT), ventricular fibrillation (VF)] and survival rate within the 5 min following reperfusion, blood levels of free radicals detected 2 min after reperfusion by electron spin resonance spectrometry, and amount of healthy myocardial tissue, measured 72 h after permanent coronary occlusion on immunohistologically stained serial sections, were evaluated. Postischemic reperfusion induced VT in all saline-treated rats, and VF and death in a high percentage of animals (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 subjected to permanent coronary occlusion, the amount of healthy myocardial tissue 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 data demonstrate, for the first time, an unforeseen property of melanocortin peptides, i.e., their ability to significantly reduce both heart ischemia/reperfusion injury and size of the ischemic area induced by permanent coronary occlusion.