Protective role of intracoronary vasoactive intestinal peptide in ischemic and reperfused myocardium.
Vasoactive intestinal peptide (VIP) has been shown to exert vasodilatory action and positive ionotropic effect on the heart and to possess free radical-scavenging ability. Because these properties are likely to make this peptide a suitable agent for myocardial preservation, we examined the role of VIP in myocardial ischemia and reperfusion. Isolated rat heart perfused by the Langendorff technique was subjected to 30 min of normothermic ischemia followed by 60 min of reperfusion. A significant amount of VIP was found to be released from the ischemic reperfused heart. The amount of VIP released from the heart increased progressively with the duration of reperfusion and paralleled the release of creative kinase from the heart. In another set of experiments, hearts were divided into two groups. The experimental group received three different doses of VIP (0.1 microM, 0.3 microM and 1 microM) 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 followed by 60 min of reperfusion. The results of our study indicated a significant improvement of myocardial functions by VIP (0.3 and 1 microM), as 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 microM only). Intracellular Ca++ ([Ca++]i) transients increased during ischemia and further increased during reperfusion. The increase in [Ca++]i transients was significantly reduced in the VIP-treated hearts. A significant amount of hydroxyl radical was detected in the ischemic reperfused heart, but the quantity of the hydroxyl radical was much lower in the VIP-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
Kalfin
R
R
Department of Surgery, University of Connecticut School of Medicine, Farmington.
Maulik
N
N
Engelman
R M
RM
Cordis
G A
GA
Milenov
K
K
Kasakov
L
L
Das
D K
DK
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D017665:Hydroxyl Radical; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology*
D017665:Hydroxyl Radical; D014660:Vasoactive Intestinal Peptide; D003402:Creatine Kinase; D002118:Calcium