Possible Ameliorative Effect of Ivabradine on the Autonomic and Left Ventricular Dysfunction Induced by Doxorubicin in Male Rats

Heart failure is a common adverse effect associated with doxorubicin treatment. The aim of this study is to investigate the effect of ivabradine treatment on doxorubicin-induced heart failure in conscious rats. Rats were treated with doxorubicin (2.5 mg/kg/d) or ivabradine (10 mg/kg/d) alone or along with doxorubicin injections. Changes in heart rate variability (HRV), baroreflex sensitivity, left ventricular (LV) function, serum cardiac troponin T, and cardiac histological features were taken as index parameters for the development of heart failure. Ivabradine significantly reduced the elevated heart rate; normalized the parameters of LV function, dP/dtmax and the relaxation time constant (Tau); reduced the elevated serum level of cardiac troponin T; and minimized the cardiac structural abnormalities in doxorubicin-treated rats. Moreover, ivabradine significantly increased the diminished time domain parameters of HRV, SDNN and rMSSD, and decreased the elevated low frequency power and the low frequency/high frequency while having no effect on the reduced high frequency power. Consistently, ivabradine significantly lowered the elevated baroreflex sensitivity measured by sodium nitroprusside. In conclusion, ivabradine ameliorated the LV dysfunction induced by doxorubicin. Moreover, ivabradine increased the overall HRV and restored the autonomic balance by reducing the sympathetic over activation. Therefore, ivabradine may have a possible therapeutic potential against doxorubicin-induced heart failure.