INHIBITION OF CARNITINE SYNTHESIS PROTECTS AGAINST LEFT-VENTRICULAR DYSFUNCTION IN RATS WITH MYOCARDIAL-ISCHEMIA

During myocardial ischemia, inhibition of the carnitine-mediated trans portation of fatty acid may be beneficial because it facilitates gluco se utilization and prevents an accumulation of fatty acid metabolites. We orally administered 3-(2,2,2-trimethyl hydrazinium) propionate (ME T), an inhibitor of carnitine synthesis, for 20 days to rats. Then we evaluated left ventricular (LV) function during brief ischemia by usin g a buffer-perfused isovolumic heart model. After 15 min of reoxy-gena tion after the transient ischemia, LV peak systolic pressure (PSP) alm ost completely returned to the baseline level in rats given MET (96 +/ - 4%), whereas it was only partially (77 +/- 16%) recovered in the pla cebo-treated rats. We induced myocardial infarction in other rats by l igating the left anterior descending coronary artery. Then the animals were given MET for 20 days, and LV function was compared. In the plac ebo-treated rats (with myocardial infarction, but without drug treatme nt), LVPSP was lower than that in the sham group [108 +/- 19 (n = 10) vs. 136 +/- 15 mmHg (n = 13); p < 0.05], and the time constant (T) of LV pressure decay was elongated (36 +/- 4 vs. 30 +/- 7 ms; p < 0.05). In MET-treated groups, however, neither PSP nor T differed from those in the sham group. In conclusion, inhibition of the carnitine-mediated transportation of fatty acid by MET protected against left ventricula r dysfunction in acute and chronic myocardial ischemia.