Biphasic-toxic effects of digoxin on doxorubicin cardiomyopathy in rats: Potential role as an indicator of acute cardiotoxicity

In this study, effects of digoxin on the cardiac electrophysiology and mechanical properties were examined in a rat model of heart failure induced by doxorubicin.

In order to induce heart failure, doxorubicin 5 mg/kg was injected to rat, i.p., once per week for 3 weeks. Heart failure was confirmed after 5 weeks, by measuring electrical, mechanical and histological changes in 12 isolated hearts. Isolated Langendorff perfused hearts were then treated with digoxin (0.1-80 µM) during a 60 min period and functional outcomes were assessed.

Effect of digoxin on the heart was biphasic. In concentrations below 80 µM (the first phase) digoxin significantly increased LVDP (left ventricular diastolic pressure) and RPP (heart rate × LVDP) .LVDP and RPP were also increased at the concentrations higher than 80 µM (the second phase). However, coronary flow, heart rate, left ventricular developed pressure and cardiac output were significantly decreased in the second phase.

Effects of digoxin on doxorubicin cardiomyopathy are biphasic. Electrical and functional changes in the second phase can be considered as an indicator of digoxin cardiotoxicity.