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 myocard ial function and metabolism altered during the course of ischemia-repe rfusion. In this study, the effect of propionyl-L-carnitine has been c ompared with that of propionate and carnitine on the performance of ra t hearts perfused with a glucose-containing medium either under normox ia, 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 impair ed by propionate, and were fully recovered by propionyl-L-carnitine. I n addition, propionyl-L-carnitine, but not propionate, reduced the fun ctional decay of mitochondria prepared from the ischemic hearts. Even in normoxic conditions propionate, unlike propionyl-L-carnitine, cause d a drastic reduction of free CoA and L-carnitine. The concomitant inc rease in lactate production and decrease in ATP content might be expla ined by the inhibition of pyruvate dehydrogenase caused by the accumul ation 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 utiliza tion of propionate in the presence of an optimal amount of ATP and fre e L-carnitine.