The cardioprotective effects of SEA0400, a novel Na(+)-Ca(2+) exchanger 
inhibitor, were examined in isolated guinea pig myocardial tissue and 
ventricular myocytes. In a coronary-perfused right ventricular tissue 
preparation, SEA0400 had no cardiosuppressive effect during normoxia and 
experimental ischemia, but enhanced the recovery of contractile force during 
reperfusion. SEA0400 had no effect on tissue ATP content during normoxia, but 
attenuated its decrease during ischemia. Treatment of ventricular myocytes with 
an ischemia mimetic solution (high K(+), glucose free, pH 6.0, gassed with N(2)) 
resulted in the depolarization of the mitochondrial membrane potential and an 
increase in cytoplasmic and mitochondrial Ca(2+) concentration, which had a 
similar time course. SEA0400 significantly delayed these changes. These results 
suggest that SEA0400 maintains mitochondrial function and tissue ATP content 
during ischemia through the inhibition of cytoplasmic and mitochondrial Ca(2+) 
overload.