Effects of ranolazine in a model of doxorubicin-induced left ventricle diastolic dysfunction

Doxorubicin (DOXO) is a highly effective anticancer drug but its clinical application is impeded by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of DOXO cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent late cardiotoxicity is warranted. Increased DOXO-dependent reactive oxygen species may explain, in part, Ca(2+) and Na(+) overload that contributes to diastolic dysfunction and development of heart failure. Therefore, we tested whether the administration of ranolazine (RAN), a selective blocker of late Na(+) current, immediately after completing DOXO therapy, can impact on diastolic dysfunction and interfere with the progression of functional decline.