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Dobutamine "stress" test and latent cardiac susceptibility to inhaled diesel exhaust in normal and hypertensive rats**
Citation:
HAZARI, M. S., J. Callaway, D. W. WINSETT, C. LAMB, N. HAYKAL-COATES, Q. T. KRANTZ, C. KING, D. L. Costa, AND A. FARRAJ. Dobutamine "stress" test and latent cardiac susceptibility to inhaled diesel exhaust in normal and hypertensive rats**. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 120(8):1088-93, (2012).
Impact/Purpose:
This study demonstrates that a single exposure to DE, an emission source complex mixture air pollutant, which is produced by the combustion of fossil fuels and contributes heavily to the environmental PM mass concentrations in the United States, produces significant risk of arrhythmia and other adverse cardiac events in normotensive and hypertensive animals. These results are important because of the known hazardous health effects of particulate air pollution, particularly in a susceptible population (i.e. those with hypertension and underlying cardiovascular disease). Since USEPA has identified particulate matter as a major respiratory irritant, these results shed light on how this toxicant produces its effects and provides a model for studying other common air pollutants. This work also fulfills air research program goals.
Description:
Background -Exercise "stress" testing is a screening tool used to determine the amount of stress for which the heart can compensate before developing abnormal rhythm or ischemia, particularly in susceptible people. Although this approach has been used to assess risk in humans exposed to air pollution, it has never been applied to rodent studies. Objective -We hypothesized that a single exposure to diesel exhaust (DE) would increase the risk of adverse cardiac events like arrhythmia and myocardial ischemia in rats undergoing a dobutamine challenge test, which can be used to mimic exercise-like stress. Methods -Wistar-Kyoto normotensive (WKY) and Spontaneously Hypertensive (SH) rats implanted with radiotelemeters and a chronic intravenous catheter were exposed whole-body to 150 ug/m3 DE (4 hours). Increasing doses of dobutamine, a beta-I adrenergic agonist, were administered to conscious unrestrained rats 24hrs later to simulate exercise while heart rate (HR) and electrocardiogram (ECG) were monitored. Results -A single exposure to DE potentiated the HR response of WKY and SH rats during dobutamine challenge and prevented heart rate recovery at rest. During peak challenge, DEexposed SH rats had lower overall heart rate variability when compared to controls, and transient ST-depression. All DE-exposed animals also had increased arrhythmias. Conclusions -These results are the first evidence that rats exhibit comparable stress-induced cardiac dysrhythmia and ischemia sensitivity to humans with a single exposure to a toxic air pollutant, particularly in the presence ofunderlying cardiovascular disease. A shift in autonomic balance and decreased compensatory capacity at such low concentrations of air pollution suggest increased risk of subsequent triggered dysfunction.