Nicotine &amp; cardiac vulnerability to fibrillation
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Epidemiological studies have shown that the incidence of atrial fibrillation (AF), rapid and irregular electrical activation of the upper chambers of the heart (disorganized wave front activity), increases with increasing age and is more prevalent in male than in female. While not lethal in and itself, AF if remained untreated causes heart failure, chest pain, stroke and increases the risk of sudden cardiac death caused by ventricular fibrillation (VF). In the US, AF remains the most common cardiac arrhythmia requiring hospitalization. Recent studies have shown that smoking increases the incidence of AF in diseased (remodeled) atria of various causes. It is however, not known how smoking influences the incidence of AF in aged atria known to manifest various forms of remodeling. Furthermore, the mechanisms by which nicotine promotes AF in the aged atria and gender differences, if at all, for enhanced vulnerability to AF with nicotine use remains undefined. The purpose of this study is to elucidate the mechanism by which nicotine promotes AF in the remodeled atria induced by aging and to determine gender differences to nicotine sensitivity for the induction of AF. 
 
 
 
 
 
 The studies will be conducted on atria isolated from rats of different ages and gender. (The National Institute on Aging maintains colonies of rats of different ages for the specific purpose of studying the effects of aging on various body functions). The effects of nicotine on atrial electrical activation patterns and properties will be visualized dynamically during heart rate acceleration using high-resolution computerized optical mapping techniques. By this method we will determine how a normal electrical activation wave front undergoes breakup leading to disorganized and irregular atrial activation, i.e., AF. 
 
 
 
 
 
 We have developed two hypotheses of activation wave front breakups: the Restitution Hypothesis and the altered cellular (junctional) coupling hypothesis of vulnerability. The first hypothesis states that when the recovery rate of cardiac excitability speeds up (slope &gt;1) a beat-to-beat cardiac instability develops during heart rate acceleration. When an atrial beat becomes unstable (i.e., too weak to propagate), a wavebreak results, leading to AF. The second hypothesis states that in the remodeled atria cell-to-cell coupling (conductance) becomes altered in aged atria and, when the heart rate is accelerated, the defective cellular communication leads to wavebreak and AF. Nicotine's ability to modulate atrial vulnerability to AF will systematically be evaluated by testing these two hypotheses in aged atria of different genders. 
 
 
 
 
 
 The elucidation of the mechanism by which nicotine promotes and maintains AF in aged atria and the determination of gender differences in the sensitivity to nicotine's pro-AF effect assume a considerable clinical significance as it helps identify subjects at high risk of developing AF with nicotine use.