Volatile Anesthetics Attenuate Sympathomimetic Actions on the Guinea Pig SA Node

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Abstract
The authors examined and compared the direct effects of three volatile anesthetic agents and three sympathomimetic agonists on transmembrane action potential (AP) characteristics and automaticity of sinoatrial (SA) nodal pacemaker cells. SA nodal tissue was isolated from guinea pig hearts and suffused in vitro with oxygenated Krebs-Ringer solution. Electrophysiologic variables measured were: amplitude of the AP, slopes of phase 4 and of phase 0 of the AP, AP duration, and spontaneous sinus rate. The authors found that 1 and 2 MAC equivalents of each anesthetic, 0.8 and 1.6 vol % halothane, 1.4 and 2.8 vol % isoflurane, and 1.7 and 3.4 vol % enflurane similarly depressed the slopes of phase 4 and 0 of the AP, prolonged AP duration, and slowed the sinus rate at 1 and 2 MAC equivalents. Isoproterenol, 0.25 .mu.M, and epinephrine, 50 .mu.M, maximally enhanced the slopes of phase 4 and 0 of the AP, shortened AP duration, and increased the sinus rate, but phenylephrine, 50 .mu.M, only moderately increased the slope of phase 4 and the sinus rate. Each of the three anesthetics caused baseline depressions of phase 4 and phase 0 slopes and of automaticity of SA nodal cells; the fall in sinus rate was counteracted, but was not reversed maximally by increasing the concentrations of isoproterenol, epinephrine, or phenylephrine. Regression analyses of linearly transformed data showed that each of the anesthetics similarly depressed basal sinus rate, so that changes in rate produced with isoproterenol and epinephrine were not different from those observed with beta agonists in the absence of anesthetics. This study suggests that halothane, isoflurane, and enflurane act in a noncompetitive way to blunt the increases in sinus rate produced with adrenergic agonists. Because the sinus rate lowering effect could not be competitively overridden by adrenergic agonists, our study supports the view that the volatile anesthetics probably interfere with intermediate or multiple steps in the mechanism of SA nodal pacemaker activity.