EFFECTS OF ISOFLURANE ON OUABAIN TOXICITY IN CANINE PURKINJE-FIBERS -COMPARISON WITH HALOTHANE

Background: Although halothane reduces digitalis toxicity, other anest hetics, notably cyclopropane, increase toxicity. This study determined the effects of isoflurane on digitalis toxicity in isolated cardiac t issue and compared these effects with those of halothane. Methods: Sta ndard microelectrode techniques were used to record action potentials from excised canine Purkinje fibers. Fibers were paced at cycle length s between 1,000 and 250 ms for 20 beats to induce delayed afterdepolar izations, which are membrane potential oscillations indicative of intr acellular Na+ and Ca2+ overload, produced in these experiments by digi talis toxicity. The digitalis glycoside ouabain, 2 X 10(-7) M, was add ed to the Tyrode's solution superfusate to induce delayed afterdepolar izations. Action potential variables and the coupling interval and amp litude of afterdepolarizations were then measured. Isoflurane (0.5%, 1 %, or 2%) was added with a calibrated vaporizer (n = 8). In a second s et of experiments (n = 10), isoflurane 1.25% or halothane 0.75% was ad ded to the superfusate. After measurements had been made, the other ag ent was substituted. Results: Ouabain produced primary and secondary d elayed afterdepolarizations, which were reduced in amplitude by isoflu rane in a dose-related manner (P = 0.0002). Action potential duration to 90% repolarization was shortened by ouabain (P = 0.009) and remaine d shortened during isoflurane administration. Action potential duratio n to 50% repolarization was shortened by isoflurane 2%. Halothane and isoflurane were equally effective in reducing the amplitude of delayed afterdepolarizations (both P = 0.0002). In three fibers, triggered ex trasystoles appeared. Halothane and isoflurane each abolished extrasys toles. In two fibers, sustained triggered activity appeared. Isofluran e abolished the arrhythmia in each fiber. Conclusions: Isoflurane and halothane are equally effective in reducing delayed afterdepolarizatio ns induced by ouabain toxicity.