Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. VI. Verapamil and fentanyl-pancuronium.

To assess the interaction between verapamil and fentanyl-pancuronium, dogs were chronically instrumented to measure heart rate; PR interval; aortic, left ventricular, and left atrial pressures; and coronary, carotid, and renal blood flows. The effect of fentanyl citrate infusion on single-dose verapamil pharmacokinetics was examined in six animals. The effects of verapamil infusion (3 micrograms.kg-1.min-1 and 6 micrograms.kg-1.min-1) were examined in the conscious state and during fentanyl infusion plus pancuronium on two separate occasions in nine dogs. In addition, the effects of fentanyl citrate (500 micrograms.kg-1 followed by 1.5 micrograms.kg-1.min-1) were examined over 1 h of infusion. Fentanyl infusion did not affect single-dose verapamil pharmacokinetics. In the conscious animals, verapamil increased heart rate and PR interval, and slightly decreased LV dP/dt. Fentanyl combined with pancuronium increased mean arterial pressure and LV dP/dt. During fentanyl infusion, verapamil decreased mean arterial pressure and LV dP/dt, increased PR interval, and did not change heart rate. The hemodynamic effects of fentanyl infusion were steady over 1 h. In contrast to the inhalational anesthetics, which alter verapamil pharmacokinetics and have mainly additive effects with verapamil on left ventricular contractility, cardiac conduction, and regional blood flows, fentanyl-pancuronium had no effect on verapamil pharmacokinetics and minimal effect on verapamil pharmacodynamics in healthy dogs.