Cardiac and thermoregulatory toxicity of residual oil fly ash in cardiopulmonary-compromised rats

Recent epidemiological studies have reported a positive association between levels of ambient particulate matter (PM) and daily morbidity and mortalit y due to respiratory or cardiovascular causes; however, toxicological evide nce supporting these findings is limited. The present study compared cardia c and thermoregulatory responses to intratracheal instillations of residual oil fly ash (ROFA) in normal and cardiopulmonary-compromised male Sprague- Dawley rats. Animals (n = 64) were implanted with radiotelemetry transmitte rs capable of continuously monitoring heart rate, core body temperature, an d electrocardiographic waveforms. Comparisons of ROFA toxicity were conduct ed between (1) healthy rats and rats with cardiopulmonary stress or disease , including (2) rats exposed to an ambient temperature of 10 degrees C, (3) rats preexposed to ozone to induce pulmonary inflammation, and (4) rats pr etreated with monocrotaline (MCT) to induce pulmonary hypertension and vasc ulitis. Animals from each regimen were instilled with 1 of 4 doses of ROFA (0, 0.25, 1.0, 2.5 mg), and telemetry data were acquired for 96 h following ROFA instillation. Dose-related hypothermia and bradycardia were observed in healthy animals following exposure to ROFA; the magnitude and duration o f these responses were potentiated in ail compromised models. Delayed hypot hermic and bradycardic responses occurred in healthy animals receiving 2.5 mg ROFA up to 48 h following instillation. These delayed responses were exa cerbated in the MCT- and 10 degrees C-exposure models, but attenuated in th e O-3-preexposed group. Additional observed effects of ROFA included induct ion of cardiac arrhythmias and increased mortality. These results demonstra te a distinct cardiac component to ROFA toxicity that agrees with epidemiol ogical findings of PM-related excess cardiovascular mortality. Furthermore, the dose-related hypothermia and bradycardia observed in rodents from this study may confound the interpretation of results from similar air pollutio n toxicology studies.