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PERSISTENCE OF PULMONARY INJURY FOLLOWING INSTILLATION OF RESIDUAL OIL FLY ASH (ROFA) IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS
Citation:
Watkinson, W P., J. P. Nolan, U P. Kodavanti, M. Schladweiler, D. W. Winsett, A. D. Ledbetter, D L. Costa, L. B. Wichers, AND R. Hauser. PERSISTENCE OF PULMONARY INJURY FOLLOWING INSTILLATION OF RESIDUAL OIL FLY ASH (ROFA) IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
PERSISTENCE OF PULMONARY INJURY FOLLOWING INSTILLATION OF RESIDUAL OIL FLY ASH (ROFA) IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS. WP Watkinson1, LB Wichers2, JP Nolan1, UP Kodavanti1, MC Schladweiler1, R Hauser3, DW Winsett1, AD Ledbetter1, and DL Costa1. 1USEPA, ORD/NHEERL/ETD/PTB, RTP, NC, USA;2UNC SPH, Chapel Hill, NC, USA; 3Harvard SPH, Cambridge, MA, USA.
Epidemiological studies have reported a consistent association between exposure to higher concentrations of ambient particulate matter (PM) and excess pulmonary-related morbidity and mortality. To examine this phenomenon, we exposed SH rats to ROFA PM and monitored changes in pulmonary function and indices of pulmonary damage. Rats were implanted with radiotelemeters to monitor electrocardiogram, heart rate, systemic blood pressure, and core temperature. Animals were divided into four groups and exposed via intratracheal instillation (IT) to suspensions of ROFA (0.0, 0.83, 3.33, 8.30 mg/kg) in saline vehicle. Telemetered rats were monitored continuously for 8d post-IT and ventilatory function was examined (Buxco Electronics) for 6h/d on post-IT days 1?4 and 7. 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. Exposure to ROFA PM caused immediate dose-related changes in ventilatory function exhibiting decreases in tidal volume (18?45%) and increases in frequency (49?123%), minute ventilation (16?26%), and enhanced pause (4?81%). Maximal responses were observed on post-IT day 1 for low and medium dose groups and on post-IT day 2 for high dose group. These effects persisted for 4d post-IT and appeared to resolve by 7d post-IT. Adverse changes in BAL indices mirrored the dose-related changes in physiological parameters, yielding increases (high dose group@24h post-IT) in protein (2?3 fold), neutrophils (10?15 fold), and LDH (7?8 fold). These studies demonstrate substantial changes in pulmonary function in SH rats after IT exposure to ROFA PM, along with significant increases in BAL indices of pulmonary injury. Further, these effects appear to persist for a over time and may contribute to the morbidity and mortality observed in humans. (Abstract does not represent USEPA policy.)