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.

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

Cappetta, Donato;PIEGARI, Elena;RAFANIELLO, Concetta;Scavone, Cristina;ROSSI, Francesco;BERRINO, Liberato;DE ANGELIS, Antonella
2017

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11591/372744
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