Preischemic and postischemic treatment with a new Na+/H+-exchange inhibitor, FR183998, shows cardioprotective effects in rats with cardiac ischemia and reperfusion

This study describes the pharmacologic profile of a new Na+/H+-exchange inh ibitor, FR183998, in anesthetized rats. FR183998 had a potent inhibitory ef fect on Na+/H+ exchange of rat lymphocytes with median inhibitory (IC50) va lue of 0.3 nM. Treatment with FR183998 (0.01-0.32 mg/kg, i.v.) reduced or c ompletely abolished ventricular fibrillation and mortality induced by 5-min ischemia followed by reperfusion, when it was administered nor only 5 min before ischemia but also I min before reperfusion. Myocardial infarct size induced by 30-min ischemia and 60-min reperfusion was reduced significantly in a dose-dependent manner by FR183998 (0.1-1.0 mg/kg, i.v.) when the drug was administered preischemically or at an early phase of ischemia. The ven tricular tachycardia and the ventricular fibrillation observed during the i schemic period also were suppressed significantly. These results indicate t hat FR183998 has a strong inhibitory effect on Na+/H+ exchange and suggest that treatment with FR183998 either before or immediately after the onset o f ischemia can prevent the occurrence of arrhythmias and myocardial cell ne crosis in situations of ischemia and reperfusion.