Comparative cardiovascular effects of verapamil, nifedipine, and diltiazem during halothane anesthesia in swine.

The cardiovascular effects of the calcium channel blockers verapamil (V), nifedipine (N) and diltiazem (D) were compared in halothane-anesthetized swine. Equipotent hypotensive doses of the three calcium channel blocking drugs were administered randomly by continuous infusion to three groups of six animals each to produce a uniform 25-30% reduction in mean systemic arterial blood pressure (BP). An additional group of six animals received sodium nitroprusside (S) to demonstrate the effects of lowering blood pressure with a pure vasodilator on this experimental preparation. Hemodynamic indices monitored before and after drug administration included ECG, mean systemic and pulmonary artery blood pressure, mean central venous and pulmonary capillary wedge pressure, thermodilution cardiac output, left ventricular pressure, and left ventricular dP/dt. All four study drug infusions reduced BP an average of 28%. V and D reduced BP by decreasing cardiac output (41% and 42%, respectively) without affecting systemic vascular resistance. N and S produced hypotension by decreasing systemic vascular resistance (36% and 21%, respectively) without affecting cardiac output. D reduced heart rate (18%) and both D and V increased the PR interval (60% and 40%, respectively). Calcium chloride (20 mg X kg-1 intravenous bolus) improved indices of myocardial contractility but did not affect drug-induced changes in cardiac electrophysiology. These data demonstrate that in this halothane-anesthetized swine model the administration of equihypotensive doses of verapamil or diltiazem has a more pronounced affect on cardiac conduction and myocardial contractility than does nifedipine, which predominantly reduces systemic vascular resistance with minimal effects on cardiac function.

Hyperkalemia and cardiovascular collapse after verapamil and dantrolene administration in swine.

The cardiovascular and neuromuscular interactions of verapamil and dantrolene were evaluated in 20 chloralose-anesthetized swine. The animals were randomly divided into three groups. Group I, ten animals, received a bolus intravenous injection of 0.1 mg . kg-1 of verapamil followed by the continuous infusion of 5 micrograms . kg-1 . min-1. This group was then randomly divided into two equal subgroups. Five of these animals, Group Ia, continued to receive the verapamil infusion alone. The other five animals, Group Ib, received dantrolene in incremental doses of 1.0, 3.3, and 5.6 mg . kg-1 while the verapamil infusion was continued. An additional group of five animals, Group II, received the same incremental doses of dantrolene but did not receive verapamil. Five control animals, Group III, received the alpha-chloralose anesthetic without dantrolene or verapamil. Neuromuscular function, as measured by twitch height, was affected only by dantrolene, which produced a dose-dependent depression. Verapamil resulted in initial decreases in heart rate, arterial blood pressure, cardiac output, left ventricular dP/dt, and an increase in PR interval. Dantrolene alone produced a mild increase in arterial blood pressure. Dantrolene administration to verapamil-pretreated animals resulted in a profound depression in cardiac function, marked elevation in serum K+ (8.0 +/- 0.7 mEq . l-1), and no change in arterial pH (7.39 +/- 0.02). Cardiac arrest preceded by complete atrioventricular heart block occurred in one animal before and in four animals after the final dantrolene dose was given to animals pretreated with verapamil. Although we cannot extrapolate data from our porcine model to humans, further studies are indicated to help evaluate a possible fatal drug interaction before verapamil and dantrolene are used concomitantly in a clinical setting.