Depression of atrial rate, atrioventricular nodal conduction, and cardiac contraction by diltiazem and volatile anesthetics in isolated hearts

Abstract

The direct effects of isoflurane, halothane, and enflurane alone or combined with diltiazem were examined in 49 isolated perfused guinea pig hearts. Recording electrodes were placed in the right atrium and left ventricular septal wall to measure spontaneous atrial rate and atrioventricular conduction time (AVCT). The right atrium was paced at 3-7 Hz (n = 10) to examine rate-dependent effects on AVCT, Wenckebach's periodicity, and ventricular response rates with atrioventricular (AV) block. Isovolumetric left ventricular pressure (LVP) was measured with a saline-filled balloon placed through the mitral valve. Hearts were perfused with oxygenated Krebs-Ringer's solution at 55 mmHg equilibrated with low or high concentrations of isoflurane (0.7 and 1.5%), halothane (0.5 and 1%), or enflurane (1.1 and 2.2%). Hearts were also perfused with a low or high concentration of diltiazem (75 and 150 ng/ml) alone and during anesthetic exposure. Significant findings of combined exposure were as follows: 1) the low isoflurane, halothane, or enflurane concentration plus a low or high diltiazem concentration decreased LVP compared with control and diltiazem alone; low isoflurane plus the high diltiazem concentration decreased LVP more than isoflurane alone. The high isoflurane, halothane, or enflurane concentration plus the low or the high diltiazem concentration decreased LVP from control, anesthetics and diltiazem alone. Diltiazem plus halothane or enflurane decreased LVP more than diltiazem plus isoflurane. 2) Diltiazem plus low or high isoflurane, halothane, or enflurane concentrations decreased spontaneous atrial rate from control and the agents alone, except the high isoflurane concentration plus the low diltiazem concentration was not greater than that of isoflurane alone. Diltiazem plus halothane or enflurane decreased atrial rate more than diltiazem plus isoflurane. 3) Low and high diltiazem concentration plus low isoflurane, halothane, or enflurane concentrations did not prolong AVCT more than the individual agents alone, but low or high diltiazem plus high isoflurane, halothane, or enflurane concentrations increased AVCT more than each anesthetic alone. In nonpaced hearts, AV block occurred only with high diltiazem plus low enflurane (23%) concentrations and the high enflurane concentration (31%). 4) In hearts paced at 5 and 6 Hz, AVCT increased above controls during a low or high concentrations of diltiazem, during enflurane, and during the low or high concentration of diltiazem plus enflurane; AVCT increased more with the low concentration of diltiazem plus enflurane than with the low diltiazem concentration alone. At 6 Hz, the high diltiazem concentration alone and low or high concentrations of diltiazem plus enflurane caused AV block; AV block was greater during the high concentration of diltiazem plus enflurane than with enflurane alone. Wenckebach's periods were increased over control for the high concentrations of diltiazem and low or high concentrations of diltiazem plus enflurane. At 6 Hz, ventricular escape rates during AV dissociation were slower with the high concentration of diltiazem plus enflurane than with low or high diltiazem concentrations, or enflurane alone. At 7 Hz, ventricular rates were slowed more with the low or high concentration of diltiazem plus enflurane than with low concentrations of diltiazem or enflurane alone. These results demonstrate that, in general, diltiazem plus the high concentration of isoflurane, halothane, or enflurane slow atrial rates, prolong AVCT, and depress left ventricular contractile function more than the agents alone. During atrial pacing, both enflurane and diltiazem increase AV nodal refractoriness (prolonged Wenckebach's periodicity) and slow the ventricular escape rate with AV dissociation; the combined effect of the low concentrations of diltiazem plus enflurane is greater than that of either alone.