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: In patients with heart disease smoking and nicotine products (gum and patch) are known to cause very rapid and irregular rhythms of the upper chambers of the heart known as atrial fibrillation (AF). AF is considered the most commonly encountered cardiac arrhythmia in clinical practice and the arrhythmia most responsible for hospitalization. Large clinical studies in man showed a cumulative 22-year incidence in new AF of 21.5 per 1,000 men and 17.1 per 1,000 women. AF poses substantial health risks, including heart failure, stroke, and sudden cardiac death. Management of AF engenders enormous expenditures, and the added costs of treating its consequences makes successful management and, if possible, the prevention of AF imperative. It is evident that identification of the factors that contribute to nicotine-induced AF carries significant clinical impact. 
 
 
 
 
 
 At present, however, the factors that modulate (enhance or decrease) nicotine-related AF remain poorly explored. Recently, it has become evident that cardiac disease processes increase the density of cardiac sympathetic nerves which spill adrenaline (equivalent of stress) and increase the incidence of AF. The phenomenon of increased sympathetic nerve density is known as "nerve sprouting." Since nicotine is known to enhance sympathetic activation to the heart, we hypothesized that nicotine promotes AF in hearts with increased sympathetic nerve sprouting. A second hypothesis of the present proposal is that decreased sympathetic nerve density, caused by sympathetic nerve sectioning, a procedure that decreases cardiac nerve input to the heart, eliminates nicotine-related AF. These two hypotheses will be tested in an animal model of myocardial infarction (MI) that produces increased sympathetic atrial nerve density. This model simulates a heart attack and allows us to test our proposed hypotheses. Recent computerized atrial mapping studies showed that AF during sympathetic activation causes rapid pacemaker-like activity in regions located outside the normal pacemaker site (ectopic focus). Such rapid activity in diseased atria with abnormal (remodeled) cellular electrical properties of the atria causes AF. 
 
 
 
 
 
 The effects of acute and chronic nicotine on AF mechanisms will be determined using high-resolution computerized mapping techniques that sample activation from several thousand sites simultaneously and generate images of activation patterns during AF. The studies will be conducted in in situ and in isolated in vitro settings. The effects of chronic nicotine will be assessed using a chronically implanted miniosmotic pump loaded with nicotine that continuously delivers nicotine that is equivalent of smoking one pack of cigarettes per day for a one-month period. The effects of acute and chronic nicotine on the formation of rapid ectopic foci will be assessed by the analysis of the detailed AF maps. Atrial single cell activity will also be recorded from rapid ectopic foci to determine the cellular mechanism of rapid pacemaker-like activity that might cause AF. 
 
 
 
 
 
 The results of the present proposal will demonstrate for the first time how atrial sympathetic nerve sprouting may modulate nicotine-related AF in hearts with chronic MI. These results may also shed light into causes of variable and unpredictable incidence of AF in smokers with heart disease. Finally, these results might help develop an effective rationale for AF prevention and perhaps even motivate smoking cessation.