ACYLCARNITINE ACCUMULATION DOES NOT CORRELATE WITH REPERFUSION RECOVERY IN PALMITATE-PERFUSED RAT HEARTS

Carnitine palmitoyltransferase-I (CPT-I) inhibitors improve postischem ic myocardial function either by decreasing muscle long-chain acylcarn itines (LCAC) during ischemia or by increasing oxidation of alternate substrates such as glucose during reperfusion. These possibilities wer e evaluated using oxfenicine, a CPT-I inhibitor, and alternate substra tes that bypass carnitine-dependent metabolism. Isolated rat hearts su bjected to 20 min of ischemia followed by 40 min of reperfusion with 1 .8 mM palmitate as exogenous substrate recovered little function durin g reperfusion. Hearts made ischemic and reperfused with palmitate and 2.4 mM hexanoate as exogenous substrates had significantly improved re perfusion function compared to palmitate-perfused hearts. Addition of 2 mM oxfenicine to palmitate-hexanoate-perfused hearts gave an additio nal small improvement in reperfusion function. At the end of ischemia, the LCAC content of hearts perfused with palmitate or hexanoate and p almitate was identical. Palmitate-, hexanoate-, and oxfenicine-perfuse d hearts had significantly decreased LCAC content at the end of ischem ia compared with hexanoate-palmitate-perfused hearts. Therefore, depre ssed reperfusion function in long-chain fatty acid-perfused hearts can be ameliorated by alternate substrates, including medium-chain fatty acids. LCAC accumulation during ischemia apparently plays only a minor role in the postischemic dysfunction of long-chain fatty acid-perfuse d hearts.