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Dobutamine cardiac "stress" test reveals increased arrhythmia risk in conscious rats after a single exposure to acrolein
Citation:
HAZARI, M. S., N. HAYKAL-COATES, D. W. WINSETT, D. L. COSTA, AND A. FARRAJ. Dobutamine cardiac "stress" test reveals increased arrhythmia risk in conscious rats after a single exposure to acrolein. Presented at Society of Toxicology 49th Annual Meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
This study examines the heart rate response and arrhythmogenicity of WKY and SH rats following a single exposure to acrolein during a dobutamine cardiac stress test. This methodology could potentially be applied to study the effects of air pollutants on the cardiovascular system.
Description:
Mild-to-moderate exercise is often used to stress the cardiovascular (CV) system of patients while monitoring them for electrocardiogram (ECG) abnormalities that may indicate underlying CV disease. We previously demonstrated that dobutamine, which increases heart rate (HR) and contractility, can serve as a reasonable challenge surrogate to reveal stress-induced cardiac electrical dysfunction in different rat strains. In this study, we hypothesized that a single inhalation exposure to a toxic air pollutant would increase the risk of arrhythmia via the dobutamine"stress"test. Wistar-Kyoto(WKY) and spontaneously hypertensive (SH) rats were surgically implanted with radiotelemeters and a chronic intravenous (iv) catheter in the left jugular vein. After recovery, rats were exposed whole-body to either air or 3ppm acrolein for 3hr. One day later, intravenous dobutamine (20, 40, 80, 160 and 320ug/kg) was administered to conscious rats while ventilatory parameters and ECG were monitored continuously. Dobutamine caused a dose-dependent increase in HR in air-exposed WKY rats, this response was potentiated in SH rats. Exposure to acrolein decreased the HR response to dobutamine in both WKY and SH rats. However, exposure to acrolein significantly increased the number of atrial premature beats, ventricular premature beats, and non-conducted P-waves triggered by the challenge in both strains relative to their controls. During the challenge, ventricular tachycardia episodes were observed in all acrolein-exposed animals but not in controls. There was no significant difference in the ventilatory parameters of either strain. In conclusion, the dobutamine stress test shows that rat strains with compromised cardiovascular systems are prone to elevated HR and arrhythmic events when compared to the healthy strain. Exposure to a toxic air pollutant may increase the risk oftriggering cardiac arrhythmias, particularly with a concomitant stress like exercise. (This abstract does not reflect EPA policy)