A new experimental model for studies of drug actions on myocardial metabolism. Application to a study of the influence of POCA.

In order to study myocardial metabolism by external detection, quantitative information on the metabolism of a gamma-emitting iodinated fatty acid (IHA) was obtained from time-activity curves of radioactivity in different compartments. A 4-compartment mathematical model was then developed; compartments 0, 1, 2, and 3 correspond respectively to vascular IHA, intracellular IHA, esterified forms, and iodide resulting from mitochondrial oxidation of IHA. We applied this model to a study of the influence of an inhibitor of fatty acid oxidation, POCA (2-[5(4 chlorophenyl) pentyl]-oxirane-2-carboxylate). Isolated rat hearts were perfused for 20 min with Krebs liquid containing increasing concentrations of POCA. IHA was then injected as a bolus at the entrance of the coronary network. The level of cardiac radioactivity was recorded for 30 min and the division into the 4 compartments was simulated at different concentrations of POCA. The drug appeared to increase the myocardial retention of IHA and slow down the speed of degradation and storage; the variations were dose-dependent. These results correspond to those obtained by intracellular analysis. The proposed method, which is reliable and sensitive, is an interesting experiment for pharmacological studies of cardiac metabolism.