title: Epinephrine-induced cardiac arrhythmias in rabbits exposed to trichloroethylene: potentiation by caffeine.
abstract: Approximately 200 000 industrial workers are exposed to trichloroethylene in the United States. Individuals intoxicated with trichloroethylene are known to develop cardiac arrhythmias. Caffeine is known to be a cardiac stimulant and is one of the drugs most widely used by the American population. Therefore, it was of interest to study the effect of caffeine on the arrhythmogenicity of trichloroethylene. Rabbits were treated with a vehicle control (1 mL/kg, ip) or caffeine (10 mg/kg, ip, 30 minutes prior to exposure) and exposed for one hour to 6000 ppm trichlorethylene under dynamic airflow conditions. Epinephrine was infused until arrhythmias occurred after 7.5, 15, 30, 45 and 60 minutes of exposure and also 15 and 30 minutes post-exposure. Serial blood samples were collected at these time points and analyzed for trichloroethylene and the two major metabolites, trichloroethanol and trichloroacetic acid. Rabbits treated with caffeine and exposed to trichloroethylene developed more arrhythmias in response to epinephrine than rabbits exposed to trichloroethylene alone, and the arrhythmias occurred sooner and in response to lower doses of epinephrine. Caffeine treatment had no effect on trichloroethylene blood concentration, but significantly decreased trichloroethanol blood levels after 45 and 60 minutes of exposure to trichloroethylene. Caffeine also reduced blood levels of trichloroacetic acid. The data indicate that caffeine can potentiate the arrhythmogenicity of trichloroethylene in rabbits.
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002110:Caffeine / Q000009:adverse effects / Q000494:pharmacology*; D005117:Cardiac Complexes, Premature / Q000139:chemically induced; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D013997:Time Factors; D014241:Trichloroethylene / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D014241:Trichloroethylene; D002110:Caffeine; D004837:Epinephrine