Phenytoin prevents epinephrine-induced arrhythmias through central nervous system in halothane-anesthetized dogs

The authors investigated the effect of phenytoin through the central nervous system on epinephrine-induced arrhythmias in halothane-anesthetized dogs. The arrhythmogenic dose (AD) of epinephrine during halothane anesthesia was determined in the presence of phenytoin (1 mg/kg), vehicle, and saline, which were administered directly into the cisterna magna. Phenytoin increased the AD of epinephrine as compared with vehicle or saline. The cerebrospinal and plasma concentration of phenytoin during the arrhythmias were 23.6 and less than 0.5 micrograms/ml, respectively. There was no significant difference in AD between the vehicle and saline groups. The same dose of phenytoin (1 mg/kg) administered intravenously did not affect the AD of epinephrine, and the plasma concentration of phenytoin during the arrhythmias was 1.2 micrograms/ml. These findings suggested that phenytoin exerts a protective effect against halothane-epinephrine arrhythmias through a central mechanism and that the central nervous system may be involved, at least in part, in the myocardial sensitization by halothane.