Cardiovascular Effects of and Interaction between Calcium Blocking Drugs and Anesthetics in Chronically Instrumented Dogs. I. Verapamil and Halothane

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Abstract
In order to assess the interaction between halothane and verapamil on the cardiovascular system, mongrel dogs were instrumented so that the following measurements could be made awake and under the influence of the drugs: aortic, left ventricular, and left atrial blood pressures; myocardial segment length shortening; heart rate and rhythm; and coronary, carotid, and renal blood flows. The effect of two infusion doses of verapamil (3 .mu.g .cntdot. kg-1 .cntdot. min-1 and 6 .mu.g .cntdot. kg-1 .cntdot. min-1 after 200 .mu.g .cntdot. kg-1 bolus) were examined awake. On a different day in the same dogs, two concentrations of halothane (1.2-low and 2.4-high % end-tidal) and the effect of the two infusion doses of verapamil during low and high halothane were studied. Thirty minutes of either infusion dose of verapamil produced only heart rate and electrocardiographic P-R interval increases in conscious dogs. Halothane produced dose-related decreases in mean aortic pressure, left ventricular maximum rate of tension development (dP/dt), and segment length shortening and increases in heart rate and left atrial pressure. Carotid blood flow was increased by low halothane concentrations and returned to control with high halothane concentrations. There were no significant changes in coronary or renal blood flow produced by halothane. Verapamil infusion during low halothane concentration produced minimal effects. However, both the 3 and 6 .mu.g .cntdot. kg-1 .cntdot. min-1 verapamil doses further depressed hearts already depressed by the high concentrations of halothane and decreased renal and carotid blood flows. Verapamil plasma levels were significantly higher during both low and high halothane concentrations than when the same dose was given to the same dogs awake. The authors conclude that: 1) the predominant effect of combination of halothane and verapamil was from halothane; 2) halothane alters the pharmacokinetics of intravenous verapamil, resulting in marked increases in plasma verapamil levels when compared with the same dose awake; 3) verapamil infusion is well tolerated during low concentrations of halothene, but the combination of high halothane concentrations and verapamil produces profound cardiovascular depression.