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Mechanistic basis of arrhythmogenic cardiac alternans following tobacco smoke exposure

Institution: University of California, Davis
Investigator(s): Crystal Ripplinger,
Award Cycle: 2019 (Cycle 29) Grant #: T29IP0365 Award: $500,000
Subject Area: Cardiovascular and Cerebrovascular Disease
Award Type: High Impact Pilot Award

Initial Award Abstract
It is known that smoking is associated with an increased incidence of abnormal heart rhythms (arrhythmias). Arrhythmias in the upper chambers of the heart (atrial fibrillation) increase risk for stroke, whereas arrhythmias in the lower chambers of the heart (ventricular tachycardia/fibrillation) pose great risk for sudden cardiac death. Therefore, understanding how and why smoking increases arrhythmia risk is of great clinical importance. We recently completed an experimental study in which we determined that mice exposed to secondhand tobacco smoke had increased susceptibility to cardiac arrhythmias, and we found that these arrhythmias were caused by abnormal calcium handling within heart cells. Tobacco smoke, however, contains many particles and chemicals and it is impossible to determine exactly which component of tobacco smoke may be contributing to abnormal calcium handling and arrhythmias. Therefore, the goal of this project is to test one chemical in tobacco smoke, nicotine, to determine if it is a contributor to arrhythmia. To do this, we will test the effects of acute nicotine application on rabbit hearts to determine its effect. We will also implant nicotine-releasing pumps in rabbits for one month to determine how long-term nicotine exposure might alter heart rhythms. The results of this study will be particularly important considering that nicotine is not only present in tobacco smoke, but also e-cigarettes, which are used by teenagers and young adults. Therefore, we hope to provide more detailed scientific information on the cardiac effects of nicotine.