Nicotine and 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: It is known that tobacco smoke aggravates the outcome (prognosis) of a disease in man. Patients with a history of a heart attack (myocardial infarction or MI) are perhaps the most vulnerable to the worsening effect of tobacco smoke. A recent carefully designed study involving a large number of patients with a history of MI, showed that smoking not only significantly increased the incidence of sudden cardiac death, but that quitting the habit also led to a significant reduction in the mortality rate in this patient population. 
 
 
 
 
 
 Sudden cardiac death in man is often caused by irregular beating (arrhythmia) of the heart. The most common cause of these potentially lethal cardiac arrhythmias is cardiac fibrillation, an irregular and rapid cardiac rhythm that resembles fluid turbulence. During fibrillation the orderly normal beatings of the heart, (like target waves that travel in sequence in a pond) is completely lost. If fibrillation occurs in the lower chambers (i.e., ventricular fibrillation of VF) the patient suddenly collapses (sudden death) requiring emergency resuscitation with electrical shock. If on the other hand, fibrillation occurs in the upper chambers of the heart (atrial fibrillation or AF) although death is not as imminent as in VF, however, AF in the long run carries significant risk of sudden cardiac death and brain stroke. At the present, it is not known by what mechanism(s) smoking precipitates these potentially lethal cardiac rhythms. The major cardiac effects of smoking are mimicked by the intake of nicotine, a major constituent of tobacco smoke, and chewing nicotine gum has been shown to directly trigger AF in susceptible patients. The aim of our research proposal, therefore, is to elucidate the mechanism(s) by which nicotine triggers cardiac fibrillation in diseased hearts.
 
 
 
 
 
 We will determine nicotine’s effect on cardiac vulnerability to fibrillation in animal models with diseased hearts that bear close resemblance to diseased human hearts prone to AF and VF. In these models, we will show, using computer generated images how nicotine converts the regular normal rhythm (target wave pattern) to fibrillation (turbulent wave pattern). In this proposal we will specifically determine nicotine’s pro-fibrillatory mechanisms in diseased hearts and the conditions under which nicotine promotes the conversion of normal cardiac rhythm (regular target waves) to fibrillation (irregular vortex-like waves). Nicotine’s pro-fibrillatory potential will also be evaluated under conditions of increased heart rates, an event that accompanies physical activity. 
 
 
 
 
 
 
 
 The result of this study will provide, for the first time, fundamental and new knowledge on the mechanism by which nicotine promotes cardiac fibrillation. This new knowledge is most relevant to the problem of smoking-induced increase in sudden cardiac death in man. It is anticipated that the results of this study will provide new and effective therapeutic strategies and encourage preventive measures designed to minimize the incidence of sudden cardiac death in smokers.