Cardioprotective effects of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on cardiac dysfunction induced by ischemia/reperfusion in isolated rat hearts

Inhibition of fatty acid metabolite accumulation may be beneficial for trea tment of cardiac dysfunction induced by ischemia. MET-88, 3-(2,2,2-trimethy lhydrazinium)propionate dihydrate, inhibits gamma -butyrobetaine hydroxylas e which catalyzes conversion of gamma -butyrobetaine to carnitine. In this study, we investigated whether MET-88 has cardioprotective effects against cardiac dysfunction induced by ischemia/reperfusion. Rats were divided into four groups: (1) control; (2) MET-88 at 50 mg/kg; (3) MET-88 at 100 mg/kg; (4) nifedipine at 30 mg/kg. MET-88 was administered orally once a day for 10 days, and nifedipine was administered orally 30 min before the experimen ts. Cardiac functions (heart rate, left ventricular systolic pressure and c oronary flow) were measured in rat working heart preparations for 30 min un der ischemia followed by 20 min under reperfusion, Myocardial carnitine lev els were measured at the end of the experiments. Before ischemia, MET-88 di d not affect cardiac functions, but nifedipine significantly increased only coronary flow. Under the ischemic condition, cardiac functions were marked ly decreased in all groups. During reperfusion, MET-88 and nifedipine promo ted recovery of cardiac functions and decreased the incidence of ventricula r fibrillation. MET-88 also prevented the accumulation of long-chain acylca rnitine induced by ischemia. These results indicated that MET-88 protected against cardiac dysfunction in ischemia/reperfusion, and preventing the acc umulation of long-chain acylcarnitine may be responsible for the cardioprot ective effects. Copyright(C) 2000 S. Karger AG, Basel.