CHRONIC RAPID ATRIAL-PACING - STRUCTURAL, FUNCTIONAL, AND ELECTROPHYSIOLOGICAL CHARACTERISTICS OF A NEW MODEL OF SUSTAINED ATRIAL-FIBRILLATION

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 sh ort-term setting. Recently, models of chronic ventricular myopathy and fibrillation have been developed after several weeks of continuous ra pid ventricular pacing. We hypothesized that chronic rapid atrial paci ng would lead to atrial myopathy, yielding a reproducible model of sus tained AF. Methods and Results Twenty-two halothane-anesthetized mongr el dogs underwent insertion of a transvenous lead at the right atrial appendage that was continuously paced at 400 beats per minute for 6 we eks. Two-dimensional echocardiography was performed in 11 dogs to asse ss the effects of rapid atrial pacing on atrial size. Atrial vulnerabi lity 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 perio d (ERP) was measured at two endocardial sites in the right atrium. Sus tained AF was defined as AF greater than or equal to 15 minutes. In an imals with sustained AF, 10 quadripolar epicardial electrodes were sur gically attached to the right and left atria. The local atrial fibrill atory cycle length (AFCL) was measured in a 20-second window, and the mean AFCL was measured at each site. Marked biatrial enlargement was d ocumented; after 6 weeks of continuous rapid atrial pacing, the left a trium was 7.8+/-1 cm(2) at baseline versus 11.3+/-1 cm(2) after pacing , and the right atrium was 4.3+/-0.7 cm(2) at baseline versus 7.2+/-1. 3 cm(2) after pacing. An increase in atrial area of at least 40% was n ecessary to induce sustained AF and was strongly correlated with the i nducibility of AF (r=.87). Electron microscopy of atrial tissue demons trated structural changes that were characterized by an increase in mi tochondrial size and number and by disruption of the sarcoplasmic reti culum. After 6 weeks of continuous rapid atrial pacing, sustained AF w as induced in 18 dogs (82%) and nonsustained AF was induced in 2 dogs (9%). AF occurred spontaneously in 4 dogs (18%). Right atrial ERP, mea sured at cycle lengths of 400 and 300 milliseconds at baseline, was si gnificantly shortened after pacing, from 150+/-8 to 127+/-10 milliseco nds and from 147+/-11 to 123+/-12 milliseconds, respectively (P<.001). This finding was highly predictive of inducibility of AF (90%). Incre ased atrial area (40%) and ERP shortening were highly predictive for t he induction of sustained AF (88%). Local epicardial ERP correlated we ll with local AFCL (R(2)=.93). Mean AFCL was significantly shorter in the left atrium (81+/-8 milliseconds) compared with the right atrium 9 4+/-9 milliseconds (P<.05). An area in the posterior left atrium was c onsistently found to have a shorter AFCL (74+/-5 milliseconds). Cryoab lation of this area was attempted in 11 dogs. In 9 dogs (82%; mean, 9. 0+/-4.0; range, 5 to 14), AF was terminated and no longer induced afte r serial cryoablation. Conclusions Sustained AF was readily inducible in most dogs (82%) after rapid atrial pacing. This model was consisten tly associated with biatrial myopathy and marked changes in atrial vul nerability. An area in the posterior left atrium was uniformly shown t o have the shortest AFCL. The results of restoration of sinus rhythm a nd prevention of inducibility of AF after cryoablation of this area of the left atrium suggest that this area may be critical in the mainten ance of AF in this model.