Chronic atrial fibrillation causes left ventricular dysfunction in dogs but not goats: experience with dogs, goats, and pigs

Abstract

Structural remodeling in chronic atrial fibrillation (AF) occurs over weeks to months. To study the electrophysiological, structural, and functional changes that occur in chronic AF, the selection of the best animal model is critical. AF was induced by rapid atrial pacing (50-Hz stimulation every other second) in pigs (n ϭ 4), dogs (n ϭ 8), and goats (n ϭ 9). Animals underwent MRIs at baseline and 6 mo to evaluate left ventricular (LV) ejection fraction (EF). Dogs were given metoprolol (50 -100 mg po bid) and digoxin (0.0625-0.125 mg po bid) to limit the ventricular response rate to Ͻ180 beats/min and to mitigate the effects of heart failure. The pacing leads in pigs became entirely encapsulated and lost the ability to excite the heart, often before the onset of sustained AF. LV EF in dogs dropped from 54 Ϯ 11% at baseline to 33 Ϯ 7% at 6 mo (P Ͻ 0.05), whereas LV EF in goats did not drop significantly (69 Ϯ 8% at baseline vs. 60 Ϯ 9% at 6 mo, P ϭ not significant). After 6 mo of AF, fibrosis levels in dog atria and ventricles increased, whereas only atrial fibrosis levels increased in goats compared with control animals. In our experience, the pig model is not appropriate for chronic rapid atrial pacing-induced AF studies. Rate-controlled chronic AF in the dog model developed HF and LV fibrosis, whereas the goat model developed only atrial fibrosis without ventricular dysfunction and fibrosis. Both the dog and goat models are representative of segments of the patient population with chronic AF. animal models; chronic atrial fibrillation; fibrosis; heart failure; rapid atrial pacing ATRIAL FIBRILLATION (AF) is the most frequent chronic arrhythmia (22) and significantly increases the risk of stroke and mortality (7). AF currently affects ϳ3 million patients in the United States alone, and its prevalence is predicted to increase to Ͼ7.5 million by the year 2050 (20). Despite significant advances in treatment options, including rhythm and rate control techniques, AF is frequently recurrent and persistent.A significant limitation in the development of broadly effective treatments for AF is that the development of the substrate that leads to longstanding persistent AF is not well understood. It is well known that "AF begets AF," or, in other words, the longer AF persists, the more likely it is that a patient will experience more AF in the future (30). Numerous studies (1,8,24,29,33,34) have demonstrated that there are significant structural and electrophysiological substrate changes that accompany chronic AF.Recent studies (14,15,26,27) have shown that whereas electrical remodeling and sustained AF may be achieved in a matter of weeks, tissue levels and structural remodeling continue over months. Patients with longstanding persistent AF exhibit different activation patterns and have higher AF recurrence rates than patients with paroxysmal AF (11,25,31). Chronic large animal models of sustained AF provide the opportunity to study the development of the substrate that leads to AF persistence and recurrence. The purpose ...

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Diverse Fibrosis Architecture and Premature Stimulation Facilitate Initiation of Reentrant Activity Following Chronic Atrial Fibrillation

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