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

摘要

Background and PurposeDoxorubicin is a highly effective anticancer drug, but its clinical application is hampered by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of doxorubicin cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent later development of cardiotoxicity is warranted. Increased doxorubicin‐dependent ROS may explain, in part, Ca²⁺ and Na⁺ overload that contributes to diastolic dysfunction and development of heart failure. Therefore, we tested whether the administration of ranolazine, a selective blocker of late Na⁺ current, immediately after completing doxorubicin therapy, could affect diastolic dysfunction and interfere with the progression of functional decline.