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EFFECTS OF INSTILLATION OF RESIDUAL OIL FLY ASH (ROFA) ON CARDIAC, PULMONARY, AND THERMOREGULATORY PARAMETERS IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS
Citation:
Watkinson, W P., J. P. Nolan, D. W. Winsett, A. D. Ledbetter, U P. Kodavanti, M. Schladweiler, D L. Costa, L. B. Wichers, R. Hauser, AND D. C. Christian. EFFECTS OF INSTILLATION OF RESIDUAL OIL FLY ASH (ROFA) ON CARDIAC, PULMONARY, AND THERMOREGULATORY PARAMETERS IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS. Presented at American Thoracic Society, Atlanta, GA, May 17-22, 2002.
Description:
EFFECTS OF INSTILLATION OF RESIDUAL OIL FLY ASH (ROFA) ON CARDIAC, PULMONARY, AND THERMOREGULATORY PARAMETERS IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS. LB Wichers1, JP Nolan2, DW Winsett2, AD Ledbetter2, UP Kodavanti2, MCJ Schladweiler2, R Hauser3, DC Christiani3, DL Costa2, and WP Watkinson2. 1UNC SPH and Curriculum in Toxicology, Chapel Hill, NC; 2US EPA, ORD/NHEERL/ETD/PTB, RTP, NC; 3Harvard SPH, Cambridge, MA USA.
Epidemiological studies have reported a robust correlation between the levels of ambient particulate matter (PM) and the incidence of morbidity and mortality, particularly among persons with cardiopulmonary disease. While similar effects have been demonstrated in animals, the mechanism/s by which these effects are mediated are unresolved. To investigate this phenomenon, we examined the effects of ROFA (a model emission PM) in SH rats (a susceptible disease model). Rats (n=16) were implanted with radiotelemeters capable of monitoring electrocardiogram (ECG), heart rate (HR), and core temperature (Tco). Animals were divided into four equal groups and exposed via intratracheal instillation (IT) to suspensions of ROFA (0.0, 0.25, 1.0, 2.5 mg) in saline vehicle. Telemetered rats were monitored for 96h post-IT while ventilatory function was examined for 6h/day on days 1-4. At 24h and 96h post-IT, subsets of rats 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 HR, while mid and high dose ROFA induced substantial dose-related decreases (40?70 bpm). ROFA-induced similar decreases in Tco (1.0?2.2 C) that did not return to control levels for several days post-IT in the high dose group. ECG abnormalities (rhythm disturbances, premature ventricular contractions) were observed primarily in the high dose group while dose-related changes in Penh were observed over the entire post-IT time period. Adverse changes in BAL indices mirrored the dose-related changes in physiological parameters, yielding increases in protein, albumin, LDH, and neutrophils (24h post-IT>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.
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