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EFFECTS OF INSTILLED AND INHALED PARTICULATE MATTER ON CARDIOPULMONARY PARAMETERS IN RATS
Citation:
Wichers, L. B., M. J. Campen, J. P. Nolan, W. H. Rowan, A. D. Ledbetter, D. W. Winsett, U P. Kodavanti, M. Schladweiler, D L. Costa, AND W P. Watkinson. EFFECTS OF INSTILLED AND INHALED PARTICULATE MATTER ON CARDIOPULMONARY PARAMETERS IN RATS. Presented at Inter. Conf. on Environ. Science and Technology, New Orleans, LA, January 23-26, 2005.
Description:
EFFECTS OF INSTILLED AND INHALED PARTICULATE MATTER ON CARDIOPULMONARY PARAMETERS IN RATS
LB Wichers (UNC - Chapel Hill; Chapel Hill, NC USA), MJ Campen (LRRI; Albuquerque, NM USA), JP Nolan, WH Rowan, AD Ledbetter, DW Winsett, UP Kodavanti, MCJ Schladweiler, DL Costa, and WP Watkinson (US EPA; Research Triangle Park, NC USA)
Numerous epidemiological studies have reported an increased incidence of morbidity and mortality following episodes of increased particulate matter (PM) air pollution. Furthermore, individuals with pre-existing cardiopulmonary disease appear to be more susceptible to the adverse effects of PM. While similar effects have been observed in toxicological studies, the mechanisms responsible for the observed cardiac and/or pulmonary responses have yet to be identified and likely depend upon particle characteristics and constituents.
The focus of our current work is to investigate the adverse effects of exposure to PM or PM surrogates, with emphasis on the elucidation of specific cardiac and pulmonary responses that might explain the epidemiological findings. Three primary methodologies are routinely used in our laboratory to investigate the effects of various PM/PM surrogates on cardiac, pulmonary, and thermoregulatory parameters in the rodent. Radiotelemetry procedures are used to continuously monitor indices of cardiac and thermoregulatory function; whole-body plethysmography is used to monitor pulmonary function; and bronchoalveolar lavage procedures are used to test for biomarkers of pulmonary inflammation and injury. Exposure capabilities include whole-body and nose-only inhalation procedures, as well as intratracheal instillation procedures. Recently we have added the capability to expose animals to dry particles via inhalation while in the whole-body plethysmograph chambers, thus enabling the collection of pulmonary function data during exposure. To date, a number of different emission, ambient, and natural source PM (e.g., oil fly ash, urban dust, concentrated ambient particulates, etc.) have been tested using a variety of compromised rodent models (e.g., systemic hypertension, pulmonary hypertension, aged, etc.). Experimental protocols have ranged from single instillation to multiple inhalation exposures, and from acute (1 day) to subchronic (11 weeks) time courses.
In general, exposure to PM or PM surrogates induced substantial decreases in indices of cardiac, pulmonary, and thermoregulatory function. These effects included decreases in heart rate and increases in the frequency and severity of arrhythmias, along with decrements in tidal volume and elevated breathing frequency. We also observed significant decreases in core temperature and increases in pulmonary biomarkers of inflammation and injury. Effects were potentiated with more toxic PM (such as residual oil fly ash) and caused significant lethality (?50%) in severely compromised animals. There were indications that soluble metals may play a crucial role in the toxicity of PM, perhaps mediated in part through the autonomic nervous system.
The results of these studies demonstrate substantial cardiopulmonary toxicity in rats after PM exposure, thus supporting epidemiological findings. While the underlying mechanisms of the adverse responses to PM are far from resolved, these studies and others from our laboratory have established a number of PM-induced effects that support biologically-plausible modes of action. (Abstract does not represent US EPA policy. This research was supported in part by EPACT826513.)