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EFFECTS OF INSTILLATION OF RESIDUAL OIL FLY ASH ON INDICES OF CARDIAC, PULMONARY, AND THERMOREGULATORY FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS
Citation:
Watkinson, W P., J. P. Nolan, U P. Kodavanti, M. Schladweiler, D. W. Winsett, J R. Lehmann, D L. Costa, AND L. B. Wichers. EFFECTS OF INSTILLATION OF RESIDUAL OIL FLY ASH ON INDICES OF CARDIAC, PULMONARY, AND THERMOREGULATORY FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
EFFECTS OF INSTILLED RESIDUAL OIL FLY ASH (ROFA) ON INDICES OF CARDIAC, PULMONARY, AND THERMOREGULATORY FUNCTION IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS. LB Wichers1, JP Nolan2, UP Kodavanti2, MCJ Schladweiler2, R Hauser3, DW Winsett2, DL Costa2, and WP Watkinson2. 1UNC School of Public Health, Chapel Hill, NC; 2US EPA, ORD/NHEERL/ETD/PTB, Research Triangle Park, NC; 3Harvard SPH, Cambridge, MA, USA.
Epidemiological studies have linked high levels of ambient particulate matter (PM) with increased morbidity and mortality and have reported that persons with cardiopulmonary disease appear to be at increased risk for these adverse effects. To further investigate this phenomenon, we have examined the effects of ROFA (a model emission PM) in SH rats (a susceptible disease model). Rats were implanted with radiotelemetry transmitters capable of monitoring electrocardiogram (ECG), heart rate (HR), and core temperature (Tco). Animals were divided into four groups and exposed via intratracheal instillation (IT) to suspensions of ROFA (0.0, 0.25, 1.0, 2.5 mg) in acidified saline vehicle. Telemetered rats were monitored continuously for 96h post-IT and ventilatory function was examined using a Buxco monitoring system for 6h/day on postexposure days 1 and 4. At 24h and 96h post-IT, subsets of animals underwent bronchoalveolar lavage (BAL) and the BAL fluid was examined for biochemical indices of pulmonary damage and inflammation. The IT exposures to vehicle and low dose ROFA caused no changes in Tco, while mid and high dose ROFA induced substantial decreases, ranging from 1.2?2.6 C. ROFA-induced decreases in HR ranged from 30?120 bpm and did not return to control levels until 24h post-IT for low dose and 72h post-IT for the mid and high dose groups. ECG abnormalities were observed primarily in the high dose ROFA group and consisted of general rhythm disturbances and premature ventricular contractions. Adverse changes in BAL indices mirrored the dose-related changes in physiological parameters, yielding greater increases in protein, albumin, and LDH at 24h post-IT compared to 96h post-IT. These studies demonstrate substantial deficits in cardiopulmonary function in SH rats after IT exposure to ROFA PM, along with significant increases in BAL indices of pulmonary injury. Toxicity appears to be greater than that reported previously in healthy rats and comparable to that observed in other compromised rodent models. The mechanism(s) by which these effects are mediated are still unresolved. (Abstract does not represent USEPA policy.)