PALMITOYL-L-CARNITINE MODIFIES THE MYOCARDIAL LEVELS OF HIGH-ENERGY PHOSPHATES AND FREE FATTY ACIDS

Long-chain acylcarnitines, such as palmitoyl-L-carnitine (PALCAR), are known to accumulate in the myocardium during ischemia. We examined whether exogenous PALCAR modifies the myocardial levels of high-energy phosphates (HEP) and free fatty acids (FFA) in the heart, and whetherd-cis-diltiazem andl-cis-diltiazem, an optical isomer having less potent Ca2+ channel blocking action thand-cis-diltiazem, attenuate the PALCAR-induced myocardial changes. Rat hearts were perfused aerobically at a constant flow according to the Langendorff's technique, while being paced electrically. PALCAR (5 μM) decreased the tissue levels of adenosine triphosphate and creatine phosphate and increased the tissue level of adenosine monophosphate, and produced mechanical dysfunction. In addition, PALCAR (5 μM) increased markedly the tissue levels of FFA, especially those of arachidonic and palmitoleic acids, and the release of creatine kinase (CK) from the myocardium. These alterations in the myocardial levels of HEP and FFA induced by PALCAR were significantly attenuated byd-cis-diltiazem (15 μM) orl-cis-diltiazem (15 μM). Both drugs also attenuated the PALCAR-induced CK release. The present study demonstrates that PALCAR modifies the tissue levels of HEP and FFA in the heart and that bothd-cis andl-cis-diltiazem protect the myocardium against the PALCAR-induced changes through mechanisms other that Ca2+ channel blocking action.