Adriamycin-induced alterations of the action potential in rat papillary muscle

The present study investigates the effects of adriamycin on the electrophysiological properties of the myocardium as monitored by intracellular recordings of the cardiac action potential. ADR was administered to rats at a dose of 20 mg·kg−1 given as a single intravenous injection or in four daily doses of 5 mg·kg−1 each. Twenty-four hours following the last injection, papillary muscles were removed and intracellular recordings of the action potential were sampled from the tissue. In another set of experiments, papillary muscles were removed from non-injected, control animals and superfused in vitro with adriamycin at a concentration of 200 (μmol·litre−1. Several parameters of the action potential were measured and compared with control values in both in vivo and in vitro experiments. In all studies, the major effect of adriamycin on the cardiac action potential was shown to be a prolongation of the duration at 20%, 50% and 95% repolarisation. Adriamycin did not appear to exert its effect by depression of cell metabolism, as supervision with NaCN or dinitrophenol reduced the action potential duration. The upstroke velocity, which is proportional to the sodium conductance, was unaltered by ADR; it appears that ADR alters conductance of calcium and /or potassium across the myocardial membrane by an as yet unknown mechanism.