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ACUTE EXPOSURE TO PARTICULATE MATTER IN A RAT MODEL OF HEART FAILURE
CARLL, A. P., N. HAYKAL-COATES, D. W. WINSETT, W. H. ROWAN, A. D. LEDBETTER, J. E. RICHARDS, A. FARRAJ, D. L. COSTA, AND W. P. WATKINSON. ACUTE EXPOSURE TO PARTICULATE MATTER IN A RAT MODEL OF HEART FAILURE. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Human exposure to ambient particulate matter (PM) has been linked to cardiovascular morbidity and mortality. This association strengthens in people with preexisting cardiopulmonary diseases—especially heart failure (HF). To better characterize the cardiovascular effects of PM, we developed a rat model of accelerated HF in Spontaneously Hypertensive Heart Failure (SHHF) rats. SHHF rats (male, 110d) were implanted with radiotelemeters capable of monitoring electrocardiogram (ECG), heart rate (HR), blood pressure (BP), and core temperature (Tco), and infused with the beta-adrenergic agonist isoproterenol (ISO, n=10; 2.5mg/kg/d s.c.) or saline (n=8) via osmotic pump for 28 days. ISO induced an immediate hypotension (mean arterial pressure ↓40%, 0h-10h) and hypothermia (Tco ↓5%, 3h-19h), and a delayed tachycardia (HR ↑54%, 26h-73h) relative to control. BP gradually returned to baseline after 12d, but HR stayed sharply elevated (↑38%) during infusion. Another hypotensive state lasting 12 days as well as stable decrements in HR (↓10%) and pulse pressure (PP ↓11%) followed cessation of ISO treatment. Whole-body plethysmography was used to assess ventilation. Enhanced respiratory pause remained elevated 1 and 2 weeks after ISO. Eighteen days post ISO, the rats were exposed on two successive days via nose-only inhalation to filtered air or HP12 (5h/d; 12 mg/m3)—an oil combustion-derived PM with a metal profile resembling ambient PM. Blood, bronchoalveolar lavage fluid, and heart and lung tissues were collected one or two days following HP12 exposure. PM exposure significantly increased pulmonary lactate dehydrogenase and serum HDL cholesterol only in ISO-treated rats. ISO treatment alone elicited focal ischemic myocardial lesions and apparent elevations in cardiac mass. ISO-treated rats exposed to HP12 had significantly increased cardiac mass relative to saline-treated rats exposed to either air or HP12. ECG was analyzed for heart rate variability and arrhythmia. There was a trend towards increased incidence and frequency of arrhythmias among rats exposed to HP12 and ISO combined. Based upon our preliminary findings, it appears that HP12 may exacerbate ISO-induced cardiac toxicity. (Abstract does not reflect EPA policy; this research was supported by EPA CT82947101.)
To better characterize the cardiovascular effects of PM, we developed a rat model of accelerated HF in Spontaneously Hypertensive Heart Failure (SHHF) rats.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
EXPERIMENTAL TOXICOLOGY DIVISION
PULMONARY TOXICOLOGY BRANCH