Doxorubicin cardiotoxicity in the rat: an in vivo characterization.

Abstract

The chemotherapeutic agent doxorubicin (DOX) is associated with a dose-dependent cardiotoxicity that can eventuate into heart failure. This study aimed to characterize the onset and degree of cardiotoxicity in rats receiving 10 mg/kg DOX administered as a single intraperitoneal injection (DOX1), 10 daily intraperitoneal injections of 1 mg/kg (DOX2), or in 5 weekly intraperitoneal injections of 2 mg/kg (DOX3). Transthoracic echocardiography measurements were recorded every week to characterize the onset and degree of cardiotoxicity in the 3 groups. An 80% mortality rate was observed at day 28 in DOX1, whereas DOX2 and DOX3 reached 80% mortality at days 107 and 98, respectively. Fractional shortening decreased by 30% at week 2 in DOX1, 55% at week 13 in DOX2, and 42% at week 13 in DOX3. In addition, cardiac function clearly differed between DOX1 and DOX3, whereas DOX2 and DOX3 were similar. These findings indicate that administration of the dose over the course of days (DOX2) or weeks (DOX3) results in a better survival rate and more classic signs of DOX-induced dilated cardiomyopathy, albeit with later onset, as compared with a single 10 mg/kg bolus injection of DOX.