AGGRAVATION OF MYOCARDIAL-INFARCTION IN THE PORCINE HEART BY CAPSAICIN-INDUCED DEPLETION OF CALCITONIN-GENE-RELATED PEPTIDE (CGRP)

The potent vasodilator calcitonin gene-related peptide (CGRP) is store d in a population of C-fiber afferents that are sensitive to capsaicin . CGRP has been suggested to have a beneficial effect in myocardial is chemia. In this study we used capsaicin pretreatment to deplete cardia c C-fiber peptide stores and tried to evaluate the role of endogenous CGRP in myocardial ischemia. Six pigs were pretreated with capsaicin ( 50 mg/kg). Forty-eight hours later, they were subjected to 40 min occl usion of the left anterior descending coronary artery. After 4 h of re perfusion, the heart was excised, and the extent of myocardial infarct ion was measured by using triphenyl tetrazolium chloride. Content of C GRP in the ischemic and the nonischemic myocardium was measured by rad ioimmunoassay. Capsaicin-treated pigs had more extensive myocardial in farction (56 +/- 6% vs. 26 +/- 8% of the area at risk; p = 0.013) and a lower myocardial content of CGRP (14 +/- 6 vs. 32 +/- 5 pmol/g; p = 0.039) compared with six untreated control pigs. Furthermore, capsaici n-treated pigs had significantly increased mean arterial blood pressur e compared with controls. This study indicates that peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. In view of its potent effects in cardiovascular regul ation, CGRP is a possible candidate for the mediation of the observed cardioprotective effect.