Jd. Gallagher, EFFECTS OF ISOFLURANE ON OUABAIN TOXICITY IN CANINE PURKINJE-FIBERS -COMPARISON WITH HALOTHANE, Anesthesiology, 81(6), 1994, pp. 1500-1510
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.