The cardiodynamic and metabolic effects of verapamil on the isolated dog heart

Summary The cardiodynamic and metabolic effects of verapamil were studied in isolated heart-lung preparations from dogs, modified to measure coronary outflow and myocardial oxygen consumption. An infusion of verapamil of 0.033 mg/min produced initially a decrease in heart rate (–5.7%) and some degree of myocardial failure 10 min after the start of the infusion, followed 10 min later by an increase in coronary outflow (+119.3%), a decrease in heart rate (–16.1%) and in myocardial oxygen consumption (–10.6%) and accentuation of the state of failure (dp/dt –34.6%, left atrial pressure +48.2%, systolic time +25.5%). Continuation of the infusion to a total dose of 1.21 ±0.12 mg of verapamil produced a severe grade of myocardial failure reflected by a decrease in cardiac output (–45.2%) and in dp/dt (–50.0%). This was accompanied by a decrease in heart rate (–26.3%) and in myocardial oxygen consumption (–27.0%). In a separate series, when the decrease in heart rate was prevented by pacing, verapamil did not lead to a significant change in myocardial oxygen consumption at any period during the infusion. Myocardial failure produced either with verapamil at constant heart rate or with pentobarbital sodium was characterized by similar changes in the cardiodynamic parameters and in both instances no significant change in myocardial oxygen consumption occurred. It may be concluded from this study that verapamil, in appropriate doses, increased coronary outflow, decreased heart rate and depressed myocardial contractile force. It also reduced myocardial oxygen consumption but this was found only when a proportionate decrease in heart rate occurred. Verapamil, therefore, in concentrations which are sufficient to produce a marked degree of myocardial failure, as reflected by a reduction in cardiac output of about 50%, does not possess a direct myocardial metabolic effect with consequent reduction in myocardial oxygen requirement.