Contrasting effects of propionate and propionyl-L-carnitine on energy-linked processes in ischemic hearts.
Propionyl-L-carnitine, unlike L-carnitine, is known to improve myocardial function and metabolism altered during the course of ischemia-reperfusion. In this study, the effect of propionyl-L-carnitine has been compared with that of propionate and carnitine on the performance of rat hearts perfused with a glucose-containing medium either under normoxia, ischemia, or postischemic reperfusion. In the postischemic phase, contractile parameters were partially restored both in the control and in the propionate plus carnitine-treated hearts, were markedly impaired by propionate, and were fully recovered by propionyl-L-carnitine. In addition, propionyl-L-carnitine, but not propionate, reduced the functional decay of mitochondria prepared from the ischemic hearts. Even in normoxic conditions propionate, unlike propionyl-L-carnitine, caused a drastic reduction of free CoA and L-carnitine. The concomitant increase in lactate production and decrease in ATP content might be explained by the inhibition of pyruvate dehydrogenase caused by the accumulation of propionyl-CoA. Indeed, when pyruvate was the only oxidizable substrate, propionate induced a gradual decrease in developed pressure, which was largely prevented by L-carnitine. The protective effect of propionyl-L-carnitine may be a consequence of the anaplerotic utilization of propionate in the presence of an optimal amount of ATP and free L-carnitine.
Di Lisa
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F
Dipartimento di Chimica Biologica, Università di Padua, Italy.
Menabò
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R
Barbato
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R
Siliprandi
N
N
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003065:Coenzyme A / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D004952:Esters / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D004952:Esters; D011422:Propionates; C003223:propionylcarnitine; C029658:propionic acid; D002331:Carnitine; D003065:Coenzyme A