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 stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP has been suggested to have a beneficial effect in myocardial ischemia. In this study we used capsaicin pretreatment to deplete cardiac 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 40min occlusion of the left anterior descending coronary artery. After 4 h of reperfusion, the heart was excised, and the extent of myocardial infarction was measured by using triphenyl tetrazolium chloride. Content of CGRP in the ischemic and the nonischemic myocardium was measured by radioimmunoassay. Capsaicin-treated pigs had more extensive myocardial infarction (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, capsaicin-treated pigs had significantly increased mean arterial blood pressure 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 regulation, CGRP is a possible candidate for the mediation of the observed cardioprotective effect.