Influence of alterations in drug metabolism on spontaneous and epinephrine-induced cardiac arrhythmias in animals exposed to trichloroethylene
White, J.F.; Carlson, G.P.
Toxicology and Applied Pharmacology 47(3): 515-527
1979
ISSN/ISBN: 0041-008X PMID: 442092 Document Number: 142200
The effect of trichloroethylene on the cardiac rhythm and the influence of alterations in drug metabolism on the occurrence of spontaneous and epinephrine-induced arrhythmias were studied. Rabbits and rats were treated with saline or the inducing agents, phenobarbital or the polychlorinated biphenyl Aroclor 1254; or the inhibiting agents, SKF 525A [2-diethylaminoethyl 2,2-diphenylvalerate hydrochloride] or Lilly 18947 [2,4-dichloro-6-phenylphenoxyethyldiethylamine hydrobromide]; and were exposed to trichloroethylene in an inhalation chamber under dynamic airflow conditions for 1 h. Increasing doses of epinephrine (0.5-4 .mu.g/kg, i.v.) were administered after 0, 7.5, 15, 30, 45 and 60 min of exposure until arrhythmias occurred. Rabbit controls exhibited premature ventricular beats when challenged with epinephrine (1 .mu.g/kg) after 30 min of exposure. Serial blood samples were collected from rabbits and analyzed for trichloroethylene, trichloroethanol and trichloroacetic acid by gas chromatography. Rabbits treated with SKF 525A or Lilly 18947 developed more arrhythmias after shorter exposure times in response to lower doses of epinephrine than controls and had high blood concentrations of trichloroethylene. Phenobarbital-treated rabbits developed fewer arrhythmias and had lower blood concentrations of trichloroethylene. Aroclor 1254 did not alter trichloroethylene metabolism or arrhythmia development. No correlations were found between the blood concentrations of trichloroethanol and trichloroacetic acid and cardiac arrhythmias. Only those rats treated with SKF 525A developed spontaneous and epinephrine-induced arrhythmias. Trichloroethylene can precipitate spontaneous and epinephrine-induced arrhythmias in the rat and rabbit, and the rate of metabolism of trichloroethylene can alter susceptibility to the development of these arrhythmias.