Chronic rapid atrial pacing: Structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation

Abstract

Background: Despite the clinical importance of atrial fibrillation (AF), the development of chronic nonvalvular AF models has been difficult. Animal models of sustained AF have been developed primarily in the short-term setting. Recently, models of chronic ventricular myopathy and fibrillation have been developed after several weeks of continuous rapid ventricular pacing. We hypothesized that chronic rapid atrial pacing would lead to atrial myopathy, yielding a reproducible model of sustained AF. Methods and Results: Twenty-two halothane-anesthetized mongrel dogs underwent insertion of a transvenous lead at the right atrial appendage that was continuously paced at 400 beats per minute for 6 weeks. Two-dimensional echo-cardiography was performed in 11 dogs to assess the effects of rapid atrial pacing on atrial size. Atrial vulnerability was defined as the ability to induce sustained repetitive atrial responses during programmed electrical stimulation and was assessed by extrastimulus and burst-pacing techniques. Effective refractory period (ERP) was measured at two endocardial sites in the right atrium. Sustained AF was defined as AF ≥15 minutes. In animals with sustained AF, 10 quadripolar epicardial electrodes were surgically attached to the right and left atria. The local atrial fibrillatory cycle length (AFCL) was measured in a 20-second window, and the mean AFCL was measured at each site. Marked biatrial enlargement was documented; after 6 weeks of continuous rapid atrial pacing, the left atrium was 7.8 ± 1 cm2 at baseline versus 11.3 ± 1 cm2 after pacing, and the right atrium was 4.3 ± 0.7 cm2 at baseline versus 7.2 ± 1.3 cm2 after pacing. An increase in atrial area of at least 40% was necessary to induce sustained AF and was strongly correlated with the inducibility of AF (r = .87). Electron microscopy of atrial tissue demonstrated structural changes that were characterized by an increase in mitochondrial size and number and by disruption of the sarcoplasmic reticulum. After 6 weeks of continuous rapid atrial pacing, sustained AF was induced in 18 dogs (82%) and nonsustained AF was induced in 2 dogs (9%). AF occurred spontaneously in 4 dogs (18%). Right atrial ERP, measured at cycle lengths of 400 and 300 milliseconds at baseline, was significantly shortened after pacing, from 150 ± 8 to 127 ± 10 milliseconds and from 147 ± 11 to 123 ± 12 milliseconds, respectively (P