Halothane opposes
cardiotoxicity of neutral-
sugar digitalis compounds in intact animals, presumably by depressing a sympathetic component of arrhythmogenesis. However,
halothane also produces a dose-related reduction in arrhythmogenicity of
ouabain in isolated canine Purkinje fibers, suggesting that the
anesthetic may oppose direct mechanisms of
cardiotoxicity as well. The present study examined in vivo and in vitro the effect of
halothane on the arrhythmogenicity of
ASI-222 (3-beta-O[4-amino-4-6-dideoxy-beta-D-galactopyranosyl] digitoxigen in HCl), a highly polar aminocardenolide with no sympathetic component to
cardiotoxicity. For in vivo studies,
ASI-222 was infused at a rate of 1 microgram/kg/min until appearance of third-degree atrioventricular (
AV) block or sustained ventricular arrhythmias in 5 conscious (control) and 6
halothane-anesthetized (1.4% end-tidal) dogs. For in vitro studies, standard
microelectrode techniques were used to measure action potentials (AP) in seven excised canine Purkinje fibers superfused with oxygenated
Krebs-Henseleit buffer. AP were recorded during control superfusion, after induction of toxicity with 10(-7) M
ASI-222, and during exposure to 0.5, 1.0, and 2.0%
halothane. Purkinje fibers were paced at 500-ms cycle lengths (CL) for 20 beats, and the amplitude of delayed afterdepolarizations (DAD) were recorded. Pacing at 250 ms CL was used to trigger ectopy. In vivo studies showed no difference in the cardiotoxic dose of
ASI-222 between control dogs and those anesthetized with 1.4%
halothane. However, in 4 of 6 anesthetized dogs, acutely increasing the inspired
halothane concentration suppressed arrhythmias once end-tidal concentration were >2.2%.(ABSTRACT TRUNCATED AT 250 WORDS)