Contrasting effects of propionate and propionyl-L-carnitine on energy-linked processes in ischemic hearts

• Published in: The American journal of physiology Vol. 267; no. 2 Pt 2; pp. H455 - H461
• Main Authors: Di Lisa, F, Menabò, R, Barbato, R, Siliprandi, N
• Format: Journal Article
• Language: English
• Published: United States 01-08-1994
• Subjects: Animals; Cardiotonic Agents - pharmacology; Carnitine - analogs & derivatives; Carnitine - metabolism; Carnitine - pharmacology; Coenzyme A - metabolism; Energy Metabolism - drug effects; Esters - metabolism; In Vitro Techniques; Male; Mitochondria, Heart - drug effects; Myocardial Contraction - drug effects; Myocardial Ischemia - metabolism; Myocardial Reperfusion; Myocardium - metabolism; Propionates - pharmacology; Rats; Rats, Wistar
• ISSN: 0002-9513
• DOI: 10.1152/ajpheart.1994.267.2.h455

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.