Age-related changes in electrocardiographic responses to trichloroethylene inhalation in conscious rats

Age-related effects of trichloroethylene (TRI) inhalation on heart rate (HR), its circadian rhythm, the incidence of spontaneous bradyarrhythmias (BA) and ventricular premature contractions (VPC) were examined in conscious rats, as was the dependence of arrhythmias on sleep-wakefulness. Indwelling electrodes were used for simultaneous electrocardiographic (ECG), electroencephalographic (EEG) and electromyographic (EMG) measurements in 2, 13, 20 and 26-month old rats. The rats were exposed for 8 hours to 300 ppm TRI followed by exposure to clean air for 7 days, after which they were exposed to 1,000 ppm for 8 hours. The polygraphic recordings were made during 8-hr exposures and for 28 hours thereafter. Control values for all physiological parameters were measured during 36-hr exposure to clean air. The exposure to TRI exacerbated an age-dependent decrease in HR and its circadian amplitude. Although the spontaneous BA incidence decreased with advancing age, the ratio of the number of BA episodes during the post-exposure period after TRI exposure to those during the corresponding period of clean-air exposure increased more pronouncedly for 20 and 26-month old rats than for 2 and 13-month old rats. The number of spontaneous VPC episodes increased for 20 and 26-month old rats but was not affected by the exposure to TRI. Gas chromatographic analysis of TRI and free trichloroethanol (TRI-OH) in the brain and blood of the TRI-exposed rats revealed the prolonged half-life of TRI and the delayed clearance of free TRI-OH from the tissues with advancing age. The age-related exacerbation of those ECG responses to TRI inhalation appears to be brought about in part by the age-related change in the pharmacokinetics of TRI and TRI-OH.