L-
Propionyl carnitine has been shown to improve the heart's mechanical recovery and other metabolic parameters after
ischemia-reperfusion. However, the mechanism of protection is unknown. The two dominating hypotheses are: (i) L-
propionyl carnitine can serve as an energy source for heart muscle cells by being enzymatically converted to
propionyl-CoA and subsequently utilized in the Krebs cycle (a metabolic hypothesis), and (ii) it can act as an antiradical agent, protecting myocardial cells from oxidative damage (a
free radical hypothesis). To test the two possible pathways, we compared the protection afforded to the
ischemia-reperfused hearts by L-
propionyl carnitine and its optical isomer, D-
propionyl carnitine. The latter cannot be enzymatically utilized as an energy source. The Langendorff perfusion technique was used and the hearts were subjected to 40 min of
ischemia and 20 min of reperfusion. In analysis of
ischemia-reperfused hearts, a strong correlation was found between the recovery of mechanical function and the presence of
protein oxidation products (
protein carbonyls). Both propionyl carnitines efficiently prevented
protein oxidation but L-
propionyl carnitine-perfused hearts had two times greater left ventricular developed pressure. The results indicate that both metabolic and antiradical pathway are involved in the protective mechanism of L-
propionyl carnitine. To obtain a better insight of the antiradical mechanism of L-
propionyl carnitine, we compared the ability of L- and D-propionyl carnitines,
L-carnitine, and
deferoxamine to interact with: (i) peroxyl radicals, (ii)
oxygen radicals, and (iii)
iron. We found that none of the
carnitine derivatives were able to scavenge peroxyl radicals or
superoxide radicals. L- and D-
propionyl carnitine and
deferoxamine (not
L-carnitine) suppressed
hydroxyl radical production in the Fenton system, probably by chelating the
iron required for the generation of
hydroxyl radicals. We suggest that L-
propionyl carnitine protects the heart by a dual mechanism: it is an efficient fuel source and an antiradical agent.