Inhibition of
fatty acid metabolite accumulation may be beneficial for treatment of cardiac dysfunction induced by
ischemia.
MET-88,
3-(2,2,2-trimethylhydrazinium)propionate dihydrate, inhibits
gamma-butyrobetaine hydroxylase 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 experiments. Cardiac functions (heart rate, left ventricular systolic pressure and coronary flow) were measured in rat working heart preparations for 30 min under
ischemia followed by 20 min under reperfusion. Myocardial
carnitine levels were measured at the end of the experiments. Before
ischemia,
MET-88 did not affect cardiac functions, but
nifedipine significantly increased only coronary flow. Under the ischemic condition, cardiac functions were markedly decreased in all groups. During reperfusion,
MET-88 and
nifedipine promoted recovery of cardiac functions and decreased the incidence of
ventricular fibrillation.
MET-88 also prevented the accumulation of long-chain
acylcarnitine induced by
ischemia. These results indicated that
MET-88 protected against cardiac dysfunction in
ischemia/reperfusion, and preventing the accumulation of long-chain
acylcarnitine may be responsible for the cardioprotective effects.