Effects and interaction of verapamil and volatile anesthetics on the isolated perfused guinea pig heart

The direct cardiac effects of volatile anesthetics and calcium channel blockers are obscured in vivo by autonomic reflexes and other extrinsic influences. The authors examined the direct in vitro effects of verapamil and the volatile anesthetics, halothane (HAL), enflurane (ENF), and isoflurane (ISO), in the isolated guinea pig heart. Each heart (N = 36) was perfused at constant pressure with an oxygenated Krebs-Ringer solution at 36 degrees C. Recording electrodes were placed in the right atrium, septum, and right ventricular wall. Left ventricular pressure (LVP) and coronary flow were measured. The combination of 75 or 150 ng/ml verapamil and 0.7 or 1.4 minimum alveolar concentrations (MAC) of each of the three anesthetics dose-dependently depressed spontaneous atrial rate (HR) and peak LVP, and prolonged atrial-septal (AV) time and intraventricular conduction time (IVCT). ENF decreased HR and LVP and increased IVCT more than did HAL or ISO at each anesthetic level. The combination of either level of ENF and 150 ng/ml verapamil reduced HR more than did the same level of verapamil with HAL or ISO; 1.4 MAC ENF with 150 ng/ml verapamil also caused sinus arrest in 17% of hearts. Although ENF, HAL, and ISO alone similarly depressed AV time, 1.4 MAC ENF synergistically increased, and 1.4 HAL and ISO additively increased, the delay in AV time due to each level of verapamil. In addition, 1.4 MAC ENF caused significant 25% and 67% incidences of complete AV block with low and high verapamil levels, respectively. Both levels of ENF with verapamil also increased IVCT more than did HAL or ISO with verapamil.