Effects of isoflurane on ouabain toxicity in canine Purkinje fibers. Comparison with halothane.
BACKGROUND
Although halothane reduces digitalis toxicity, other anesthetics, notably cyclopropane, increase toxicity. This study determined the effects of isoflurane on digitalis toxicity in isolated cardiac tissue and compared these effects with those of halothane.


METHODS
Standard microelectrode techniques were used to record action potentials from excised canine Purkinje fibers. Fibers were paced at cycle lengths between 1,000 and 250 ms for 20 beats to induce delayed afterdepolarizations, which are membrane potential oscillations indicative of intracellular Na+ and Ca2+ overload, produced in these experiments by digitalis toxicity. The digitalis glycoside ouabain, 2 x 10(-7) M, was added to the Tyrode's solution superfusate to induce delayed after-depolarizations. Action potential variables and the coupling interval and amplitude of afterdepolarizations were then measured. Isoflurane (0.5%, 1%, or 2%) was added with a calibrated vaporizer (n = 8). In a second set of experiments (n = 10), isoflurane 1.25% or halothane 0.75% was added to the superfusate. After measurements had been made, the other agent was substituted.


RESULTS
Ouabain produced primary and secondary delayed afterdepolarizations, which were reduced in amplitude by isoflurane in a dose-related manner (P = 0.0002). Action potential duration to 90% repolarization was shortened by ouabain (P = 0.009) and remained shortened during isoflurane administration. Action potential duration 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 extrasystoles appeared. Halothane and isoflurane each abolished extrasystoles. In two fibers, sustained triggered activity appeared. Isoflurane abolished the arrhythmia in each fiber.


CONCLUSIONS
Isoflurane and halothane are equally effective in reducing delayed afterdepolarizations induced by ouabain toxicity.
Gallagher
J D
JD
Department of Anesthesiology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshier 03756-0001.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005117:Cardiac Complexes, Premature / Q000139:chemically induced / Q000188:drug therapy; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D010042:Ouabain / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology
D010042:Ouabain; D007530:Isoflurane; D006221:Halothane