Actions of phenylephrine, isoproterenol, and epinephrine with halothane on endocardial conduction and activation in canine left ventricular papillary muscles.
BACKGROUND
Myocardial sensitization by halothane to the arrhythmogenic effects of epinephrine involves synergistic actions mediated by alpha 1- and beta-adrenoceptors. Halothane potentiates a transient a1-adrenoceptor-mediated negative dromotropic effect of epinephrine on Purkinje fibers. This study examines how halothane alters the actions of alpha 1- and beta-agonists and epinephrine on endocardial conduction.


METHODS
Superfused canine papillary muscles were mapped to locate a Purkinje-ventricular muscle junction (PVJ), and bipolar electrodes were placed to measure Purkinje and endocardial conduction velocity and PVJ conduction time during stimulation of the Purkinje layer. The effects of exposure to 5 microM phenylephrine, 1 microM isoproterenol, or 5 microM epinephrine on conduction were determined in the absence and presence of 0.4 mM halothane in three groups of 10 preparations.


RESULTS
Isoproterenol slightly increased Purkinje conduction velocity and markedly improved conduction at the PVJ and in the endocardium similarly in the presence or absence of halothane. Phenylephrine depressed Purkinje velocity (-12%) only in the presence of halothane and did not slow conduction at the PVJ or in the myocardium. Epinephrine transiently depressed Purkinje velocity, more so with (-22%) than without (-12%) halothane (P < or = 0.01), and simultaneously facilitated conduction at the PVJ and in the myocardium.


CONCLUSIONS
The prodysrhythmic actions of epinephrine with halothane may involve disparate effects on conduction, including speeding on conduction at the PVJ and in the myocardium, similar to that produced by isoproterenol, accompanied by simultaneous but transient alpha 1-mediated depression of conduction in the Purkinje system.
Vodanovic
S
S
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Turner
L A
LA
Hoffmann
R G
RG
Kampine
J P
JP
Bosnjak
Z J
ZJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology*; D016276:Ventricular Function
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D010656:Phenylephrine; D007545:Isoproterenol; D006221:Halothane; D004837:Epinephrine