(Circulation. 1995;91:1588-1595.)
© 1995 American Heart Association, Inc.
Articles |
Chronic Rapid Atrial Pacing
Structural, Functional, and Electrophysiological Characteristics of a New Model of Sustained Atrial Fibrillation
From the Departments of Medicine (C.A.M., G.J.K., D.L.J.), Physiology (D.L.J.), and Pathology (C.M.G.), University of Western Ontario, and the Heart and Circulation Group, The John P. Robarts Research Institute (C.A.M., G.J.K., D.L.J), London, Ontario, Canada.
Correspondence to Carlos A. Morillo, MD, Cardiovascular Physiology, Rm 3C-124, McGuire VA Medical Center, 1201 Broad Rock Blvd, Richmond, VA 23249.
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 echocardiography 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<.001). This finding was highly predictive
of inducibility of AF (90%). Increased atrial area (40%) and ERP
shortening were highly predictive for the induction of sustained AF
(88%). Local epicardial ERP correlated well with local AFCL
(R2=.93). Mean AFCL was significantly shorter in
the left atrium (81±8 milliseconds) compared with the right atrium
94±9 milliseconds (P<.05). An area in the posterior left
atrium was consistently found to have a shorter AFCL (74±5
milliseconds). Cryoablation 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 after serial cryoablation.
Conclusions Sustained AF was readily inducible in most dogs (82%) after rapid atrial pacing. This model was consistently associated with biatrial myopathy and marked changes in atrial vulnerability. An area in the posterior left atrium was uniformly shown to have the shortest AFCL. The results of restoration of sinus rhythm and prevention of inducibility of AF after cryoablation of this area of the left atrium suggest that this area may be critical in the maintenance of AF in this model.
Key Words: fibrillation • electrophysiology
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