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 mortality due to respiratory or cardiovascular causes; however, toxicological evidence supporting these findings is limited. The present study compared cardiac 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 transmitters capable of continuously monitoring heart rate, core body temperature, and electrocardiographic waveforms. Comparisons of ROFA toxicity were conducted between (1) healthy rats and rats with cardiopulmonary stress or disease, including (2) rats exposed to an ambient temperature of 10° C, (3) rats preexposed to ozone to induce pulmonary inflammation, and (4) rats pretreated with monocrotaline (MCT) to induce pulmonary hypertension and vasculitis. 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 of these responses were potentiated in all compromised models. Delayed hypothermic and bradycardic responses occurred in healthy animals receiving 2.5 mg ROFA up to 48 h following instillation. These delayed responses were exacerbated in the MCT-and 10°C-exposure models, but attenuated in the 03-preexposed group. Additional observed effects of ROFA included induction of cardiac arrhythmias and increased mortality. These results demonstrate a distinct cardiac component to ROFA toxicity that agrees with epidemiological 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 pollution toxicology studies.