Oxfenicine-induced accumulation of lipid in the rat myocardium

Oxfenicine inhibits myocardial metabolism of nonesterified fatty acids (NEFA). The purpose of the present study was to examine the effects of oxfenicine on triglyceride accumulation and the development of histologically visible lipid droplets. The beta-agonist isoproterenol was used to induce elevated arterial NEFA. Four groups of rats were used in the experiment (12 to 14 rats in each group), and each group received two subcutaneous injections, the second injection 25 min after the first, of oxfenicine-isoproterenol, oxfenicine-saline, saline-isoproterenol and saline twice, respectively. One hour after the second injection, the rats were anesthetized, and the hearts from six rats from each group were quickly removed and frozen for later analysis of triglyceride content. From the remaining rats blood samples were drawn for NEFA analysis, and biopsies were taken from the left ventricular wall before the hearts were frozen in liquid nitrogen and prepared for analysis of esters of carnitine and CoA. Quantitative morphometric techniques were used to determine the fractional volume of lipid droplets in myocardial biopsies. Our results show a marked increase in the triglyceride and lipid droplet content in all groups receiving oxfenicine or isoproterenol. The effect was most pronounced after treatment with both drugs. The close association between the increase in triglyceride and lipid droplet supports the notion that the lipid droplets are composed of triglycerides. Our finding that oxfenicine induces lipid droplet accumulation independent of NEFA increase supports the hypothesis that oxfenicine exerts its effect by inhibiting carnitine acyl transferase.