Fibrillatory Conduction in the Atrial Free Walls of Goats in Persistent and Permanent Atrial Fibrillation

Abstract

Background-Over a time course of months, the stability of atrial fibrillation (AF) gradually increases and the efficacy of pharmacological cardioversion declines both in humans and in animal models. Changes in fibrillatory conduction over this period largely are unexplored. Methods and Result-Goats were instrumented with an atrial endocardial pacemaker lead and a burst pacemaker. AF was maintained for 3 weeks (short-term AF [ST], nϭ10) or 6 months (long-term AF [LT], nϭ7). AF could be cardioverted pharmacologically at the early time point (persistent AF), but not at the later time point (permanent AF). At follow-up, a high-resolution mapping electrode was used to record epicardial conduction patterns in the free walls of the right atrium (RA) and left atrium (LA). A new method for mapping of fibrillation waves was used to describe AF conduction patterns. Wavefronts propagated uniformly during slow pacing in both groups, although conduction velocity was significantly lower in the LT group (LA, 93Ϯ14 versus 72Ϯ10 cm/s; RA, 94Ϯ8 versus 78Ϯ8 cm/s). Median AF cycle length (AFCL) was not significantly different between the groups. However, the LT group showed highly complex activation patterns during AF, with an increased number of simultaneously propagating waves (LT group RA, 8.4Ϯ3.0 waves/AFCL; LA, 12.8Ϯ2.4 waves/AFCL; versus ST group RA, 4.3Ϯ2.2 waves/AFCL; LA, 4.5Ϯ2.5 waves/AFCL). Fibrillation waves in the LT group showed pronounced dissociation with large activation time differences. The incidence of waves newly appearing within the recording area also was increased in both atria. These alterations in conduction were accompanied by myocyte hypertrophy and increased endomysial fibrosis. Conclusions-Long-term AF in goats leads to dissociated conduction in the atrial free walls that may contribute to increased AF stability. (Circ Arrhythm Electrophysiol. 2010;3:590-599.)

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

“…The limited data available from chronic AF studies of Ͼ3 mo of AF have demonstrated that whereas electrical remodeling occurs in hours to days, structural remodeling occurs over weeks to months. Recent studies (14,15,26,27) have shown that important conduction changes and structural remodeling occur as AF persists from a few weeks to several months in duration. Eckstein et al (14) studied the time course of structural and electrophysiologic remodeling in goats at baseline and after 3 wk and 6 mo of RAP.…”

“…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).…”

“…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).…”

Driver Domains in Persistent Atrial Fibrillation

“…Although AF could be terminated pharmacologically after few weeks, it could not be drug cardioverted after 6 months. 23 Based on these works, the prevailing mechanism of AF remodeling in humans is thought to be the multiplication of randomly circulating waves associated with a decreased atrial refractory period and heterogeneous tissue structure. The current study suggests different time-critical mechanisms for persistent AF in humans.…”

The Rotor Revolution

“…2,3 Advocates of this high spatial resolution mapping argue that the answer lies in the microscopic detail. That high resolution mapping has revealed evidence of endocardial-epicardial dissociation, 4 complex fibrillatory waves, 5 and longitudinal dissociation of myofibrils (Figure 1) 3,6 suggests that the causative mechanism is anarchical and perpetuated by generalized, diffuse processes, leading to widely distributed, complex microreentry. This is portrayed as a completely different concept from that revealed by mapping that is necessarily global and simultaneous, albeit of low spatial resolution.…”