Verapamil, propranolol, and hydralazine protect against the acute cardiac depression induced by adriamycin

The apex ejecting isolated rat heart perfused with media containing 3 X 10(-5) mol . litre-1 adriamycin for 40 min demonstrated the following changes in contraction patterns: (a) a ten-fold increase in end-diastolic pressure; (b) a 45% decrease in developed pressure; (c) a 17% decrease in coronary flow; (d) a 27% increase in time to peak pressure; (e) a 26% increase in time for pressure to fall 50% during relaxation; and (f) a 65% decrease in maximum (+) and (-) dP/dt. In rats pretreated 1 h before death, verapamil, propranolol, and hydralazine significantly attenuated the cardiac depression produced by adriamycin. The combinations of verapamil and hydralazine, or propranolol and hydralazine were especially efficacious. Particularly striking was the protection afforded against an increase in diastolic pressure. Digoxin pretreatment afforded no protection. It is postulated that the acute depressive effects of adriamycin may be related to calcium overload.