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Cardiomyopathy confers susceptibility to particulate matter-induced oxidative stress, vagal dominance, arrhythmia, pulmonary inflammation in heart failure-prone rats
Carll, A., N. Coates, D. Winsett, M. Hazari, A. Ledbetter, J. Richards, D. Costa, AND A. Farraj. Cardiomyopathy confers susceptibility to particulate matter-induced oxidative stress, vagal dominance, arrhythmia, pulmonary inflammation in heart failure-prone rats. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, 27(2):100-12, (2015).
Acute exposure to ambient fine particulate matter (PM2.5) is tied to cardiovascular morbidity and mortality, especially among those with prior cardiac injury. The mechanisms and pathophysiologic events precipitating these outcomes remain poorly understood but may involve inflammation, oxidative stress, arrhythmia, and autonomic nervous system imbalance. Cardiomyopathy results from cardiac injury, is the leading cause of heart failure, and can be induced in heart failure-prone rats through sub-chronic infusion of isoproterenol (ISO). To test whether cardiomyopathy confers susceptibility to inhaled PM2.5 and elucidate potential mechanisms, we investigated the cardiophysiologic, ventilatory, inflammatory, and oxidative effects of a single 4-hour nose-only inhalation of a metal-rich PM2.5 (580 µg/m3) in ISO-pretreated rats. During infusion, ISO (35 days * 1.0 mg/kg/day) significantly decreased blood pressure (BP) and pre-ejection period (PEP, an inverse correlate of contractility) and increased heart rate (HR) relative to saline. During the 5 days after infusion, ISO-treated rats had decreased HR and BP and increased PEP relative to saline-treated rats, indicating impaired cardiac function. Relative to clean air, PM2.5 prolonged PR-interval and decreased systolic BP during exposure; increased tidal volume, expiratory time, heart rate variability (HRV) parameters of parasympathetic tone, and atrioventricular block arrhythmias over the hours following; increased pulmonary neutrophils, macrophages, and total antioxidant status one day after exposure; and decreased pulmonary glutathione peroxidase 8 weeks after exposure, with all effects occurring exclusively in ISO-pretreated rats but not saline-pretreated rats. Ultimately, our findings indicate that cardiomyopathy confers susceptibility to the oxidative, inflammatory, ventilatory, autonomic, and arrhythmogenic effects of acute PM2.5 inhalation.
The examination of the health effects of air pollution have been hindered by a lack of a suitable methodology for yielding a heart failure model that parallels the natural etiology and progression of the disease. The impact of specific air pollution constituents, such as transition metals, on heart failure pathophysiology, has not been thoroughly examined. Residual oil fly ash (ROFA) is a major source of atmospheric iron, nickel, and vanadium (Fe, Ni, and V)—transition metals that are strongly implicated in the adverse health effects of PM. In the current study, we tested the hypothesis that acute inhalation of metal-rich PM2.5 would cause even more pronounced cardiopulmonary toxicity in rats with preexisting cardiomyopathy than in rats with minimal cardiomyopathy. To induce cardiomyopathy, young adult heart failure-prone rats were chronically infused with isoproterenol (ISO), a synthetic catecholamine. We assessed the effects of PM2.5 on cardiovascular and pulmonary physiology including electrocardiography (ECG), HRV (a measure of autonomic modulation of the heart), HR, arrhythmia, BP, and ventilatory parameters, as well as on blood and pulmonary biomarkers of injury, inflammation, and oxidative stress. In rats with cardiomyopathy, PM immediately decreased BP and prolonged PR-interval, and thereafter caused concomitant vagal dominance and bradyarrhythmias, followed by pulmonary inflammation and oxidative stress. Our findings support the mounting evidence that PM causes parasympathetic dominance, arrhythmia, and pulmonary inflammation contingent in part on underlying cardiac injury. Ultimately, this study demonstrates that preexisting cardiac injury confers susceptibility to the adverse cardiopulmonary effects of air pollution. This model may help elucidate the mechanisms by which air pollution exacerbates heart failure pathophysiology.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH