PROTECTIVE EFFECTS OF PROPIONYL-L-CARNITINE DURING ISCHEMIA AND REPERFUSION

When cardiac function in isolated rat hearts was impaired by subject them to ischemia, subsequent perfusion with propionyl-L-carnitine and related compounds increased their rate of recovery. Thus at 11 mM, both propionyl-L-carnitine and, to a lesser extent, its taurine amide, and also acetyl-L-carnitine, significantly restored cardiac function in 15 minutes after 90 minutes of either low-flow or intermittent no-flow ischemia. Carnitine itself was ineffective. Propionyl-L-carnitine also increased tissue ATP and creatine phosphate compared with controls, but did not affect the levels of long-chain acyl carnitine and coenzyme. These esters also depleted fatty acid peroxidation, as shown with malonaldehyde, and were more effective than carnitine in preventing the production of superoxide. In myocytes, propionyl-L-carnitine alone stimulated palmitate oxidation, but in rat heart homogenates, both L-carnitine and propionyl-L-carnitine did so, while acetyl-L-carnitine was actually inhibitory. Possible mechanisms for the protective action of propionyl-L-carnitine against ischemia include an increased rate of cellular transport, stimulation of fatty acid oxidation, and a reduction of free radical formation.