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PRECLINICAL STUDY

Chronic Atrial Dilation, Electrical Remodeling, and Atrial Fibrillation in the Goat

Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands

Manuscript received May 19, 2005; revised manuscript received July 29, 2005, accepted September 8, 2005.

^_* Reprint requests and correspondence: Prof. Maurits A. Allessie, Department of Physiology, University of Maastricht, PO Box 616, 6200MD-Maastricht, the Netherlands (Email: m.allessie{at}fys.unimaas.nl).

OBJECTIVES: This study was designed to investigate the mutual effects of chronic atrial dilation and electrical remodeling on the characteristics of atrial fibrillation (AF).

BACKGROUND: Both electrical remodeling and atrial dilation promote the inducibility and perpetuation of AF.

METHODS: In seven goats AF was induced during 48 h by burst pacing, both at baseline and after four weeks of slow idioventricular rhythm (total AV block). Atrial size and refractory period (AERP) were monitored together with the duration and cycle length of AF paroxysms (AFCL). After four weeks of total atrioventricular (AV) block, the conduction in both atria was mapped during AF. Six non-instrumented goats served as controls.

RESULTS: At baseline, AF-induced electrical remodeling shortened AERP and AFCL to the same extent (from 185 ± 9 ms to 149 ± 14 ms [p < 0.05] and from 154 ± 11 ms to 121 ± 5 ms [p < 0.05], respectively). After four weeks of AV block the right atrial diameter had increased by 13.2 ± 3.0% (p < 0.01). Surprisingly, in dilated atria electrical remodeling still shortened the AERP (from 165 ± 9 ms to 132 ± 15 ms [p < 0.05]) but failed to shorten the AFCL (140 ± 19 ms vs. 139 ± 11 ms [p = 0.98]). Mapping revealed a higher incidence of intra-atrial conduction delays during AF. Histologic analysis showed no atrial fibrosis but did reveal a positive correlation between the size of atrial myocytes and the incidence of intra-atrial conduction block (r = 0.60, p = 0.03).

CONCLUSIONS: In a goat model of chronic atrial dilation, AF-induced electrical remodeling was unchanged. However, AFCL no longer shortened during electrical remodeling. Thus, in dilated atria a wider excitable gap exists during AF, probably caused by intra-atrial conduction defects and a higher contribution of anatomically defined re-entrant circuits.

Abbreviations and Acronyms   AERP = atrial effective refractory period   AF = atrial fibrillation   AFCL = atrial fibrillation cycle length   AV = atrioventricular   CT = conduction time   EGAF = excitable gap during atrial fibrillation   LA = left atrium   RA = right atrium   RPAF = refractory period during atrial fibrillation

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