The effect of SEA0400, a novel Na+-Ca2+ exchanger inhibitor, on mechanical and 
electrophysiological parameters of coronary-perfused guinea-pig right 
ventricular tissue preparation was examined during no-flow ischemia and 
reperfusion. Contractile force and action potential duration were decreased 
during no-flow ischemia, while the resting tension was increased. Upon 
reperfusion, transient arrhythmias were observed and contractile force returned 
to less than 50% of preischemic values. SEA0400 (1 microM) had no effect on the 
decline in contractile force during the no-flow ischemia, but abolished the rise 
in resting tension. SEA0400 significantly improved the recovery of contractile 
force after reperfusion to about 80% of the preischemic value. SEA0400 had no 
effect on the action potential under normal conditions and during ischemia, but 
significantly improved the recovery of action potential duration after 
reperfusion. Enhancement of the recovery of contractile force during reperfusion 
by SEA0400 was also observed when the drug was applied only before and during 
the ischemic period and when the drug was applied only during reperfusion. The 
present results indicate that inhibition of Na+-Ca2+ exchanger either during 
ischemia or during reperfusion exerts cardioprotective effects and enhances the 
recovery of myocardial contractile function.