Control of the cardiac consequences of myocardial ischemia and reperfusion by L-propionylcarnitine: age-response and dose-response studies in the rat heart.
We assessed the protective effects of L-propionylcarnitine, a liposoluble analogue of carnitine, in the isolated heart from rats of different ages subjected to global ischemia and reperfusion. Hearts from neonatal (3- to 7-d-old), immature (2- to 3-wk-old), and adult rats were retrogradely perfused with a modified Krebs bicarbonate buffer and subjected to ischemia and reperfusion. L-Pro-pionylcarnitine was given either before ischemia and throughout reperfusion (protocol 1) or during reperfusion only (protocol 2). Coronary flow, heart rate, left ventricular developed pressure, and left ventricular end-diastolic pressure were measured throughout the perfusion period. Ventricular arrhythmias and creatine kinase leakage were measured at the time of reperfusion. Postischemic recovery of coronary flow and left ventricular developed pressure were age dependent and were not affected by L-propionylcarnitine, but recovery of heart rate was decreased in neonatal and immature hearts by 10(-4) M and 10(-5) M (p < 0.05), compared with controls (protocol 2). L-Propionylcarnitine always reduced creatine kinase leakage in the adult (p < 0.05) compared with controls (protocol 1). No effects on creatine kinase leakage were observed in neonatal and immature hearts. This study found that injury induced by ischemia and reperfusion was age dependent. Neonatal and immature hearts were more resistant to injury than adult hearts. The recovery of cardiac function was not affected by L-propionylcarnitine. However, in the adult rat hearts, L-propionylcarnitine given before ischemia and throughout reperfusion was protective by reducing creatine kinase leakage.
Riva
E
E
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Leopaldi
D
D
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
D002316:Cardiotonic Agents; C003223:propionylcarnitine; D002331:Carnitine