Effects of Nifedipine with Isoflurane, Halothane, or Enflurane on Automaticity, Conduction, and Contractility in Isolated Guinea Pig Hearts

Background:Calcium channel blockers and volatile anesthetics have depressant effects on cardiac function. Both groups of drugs appear to exert both qualitatively and quantitatively different effects on electrophysiologic and mechanical function. The aim of this study was to compare the direct cardiac effects of the calcium channel blocker nifedipine in the absence and presence of isoflurane, halothane, or enflurane. Methods:Guinea pig hearts (N=36) were isolated and perfused with oxygenated Krebs-Ringer solution (pH 7.4, 37° C). Recording electrodes were placed in the right atrium and ventricle to measure heart rate and atrioventricular (AV) conduction time. Isovolumetric left ventricular pressure (LVP) was measured via a latex balloon and transducer. Hearts were randomly assigned to one of three anesthetic groups at 0.7 and 1.4 minimum alveolar concentration (MAC) and treated with 15 and 30 nm nifedipine. Results:Nifedipine alone significantly decreased atrial rate and left ventricular pressure, without prolonging AV conduction. Nifedipine plus isoflurane, halothane, or enflurane did not significantly prolong AV conduction compared with the respective anesthetic agent alone, but nifedipine plus isoflurane, halothane, or enflurane significantly decreased atrial rate compared with the effect of the anesthetic alone. Halothane or enflurane plus nifedipine significantly decreased atrial rate more than nifedipine alone or isoflurane plus nifedipine. Isoflurane, halothane, or enflurane plus nifedipine significantly depressed LVP more than the respective anesthetic agent alone. Halothane or enflurane plus nifedipine also significantly depressed LVP more than Isoflurane plus nifedipine or nifedipine alone. Conclusions:This study demonstrates that the combined treatment of nifedipine and volatile anesthetics, especially enflurane, additively depresses atrial rate and contractility, but not AV conduction in vitro. In comparison with results reported previously, these effects appear less pronounced than those of the combination of volatile agents with diltiazem and, especially, verapamil.