PROTECTIVE ROLE OF INTRACORONARY VASOACTIVE-INTESTINAL-PEPTIDE IN ISCHEMIC AND REPERFUSED MYOCARDIUM

Vasoactive intestinal peptide (VIP) has been shown to exert vasodilato ry action and positive ionotropic effect on the heart and to possess f ree radical-scavenging ability. Because these properties are likely to make this peptide a suitable agent for myocardial preservation, we ex amined the role of VIP in myocardial ischemia and reperfusion. Isolate d rat heart perfused by the Langendorff technique was subjected to 30 min of normothermic ischemia followed by 60 min of reperfusion. A sign ificant amount of VIP was found to be released from the ischemic reper fused heart. The amount of VIP released from the heart increased progr essively with the duration of reperfusion and paralleled the release o f creatine kinase from the heart. In another set of experiments, heart s were divided into two groups. The experimental group received three different doses of VIP (0.1 mu M, 0.3 mu M and 1 mu M) before ischemia . After perfusing the isolated heart with VIP for 15 min, ischemia was induced for 30 min by terminating the coronary flow, which was follow ed by 60 min of reperfusion. The results of our study indicated a sign ificant improvement of myocardial functions by VIP (0.3 and 1 mu M), a s evidenced by enhanced left ventricular functions and coronary flow, and reduction of tissue injury, as judged by the decrease in creatine kinase release (0.3 mu M only). Intracellular Ca++ ([Ca++],) transient s increased during ischemia and further increased during reperfusion. The increase in [Ca++], transients was significantly reduced in the VI P-treated hearts. A significant amount of hydroxyl radical was detecte d in the ischemic reperfused heart, but the quantity of the hydroxyl r adical was much lower in the VIP-treated group. In vitro studies demon strated that VIP exerted relaxation effects on the smooth muscles isol ated from the coronary artery. The results of our study, thus, suggest that the VIP plays a significant role in modulating the myocardial is chemia and reperfusion