© 1997 American Heart Association, Inc.
Articles |
Tachycardia-Induced Changes in Na+ Current in a Chronic Dog Model of Atrial Fibrillation
From the Department of Medicine and Research Center, Montreal Heart Institute (R.G., R.F.B., E.B.-A., S.N.); the University of Montreal (S.N.); and the Department of Pharmacology and Therapeutics, McGill University (S.N.), Montreal, Quebec, Canada.
Correspondence to Stanley Nattel, MD, Montreal Heart Institute, 5000 Bélanger St East, Montreal, Quebec, Canada H1T 1C8. E-mail nattel{at}icm.umontreal.ca
Abstract We have previously shown that chronic rapid atrial
activation (400 bpm) reduces atrial conduction velocity in dogs,
contributing to the development of a substrate supporting sustained
atrial fibrillation (AF). However, the cellular and ionic mechanisms
underlying these functional changes have not been defined. We applied
whole-cell patch-clamp techniques to atrial myocytes from dogs
subjected to atrial pacing at 400 bpm for 7 days (P7, n=6) and 42 days
(P42, n=5) and compared the results with those from sham-operated dogs
similarly instrumented but without pacemaker activation (P0, n=6).
Rapid atrial pacing allowed for the induction of sustained AF in 67%
and 100% of dogs paced for 7 and 42 days, respectively, and
significantly decreased conduction velocity under P7 and P42
conditions. In dogs paced for 7 days, Na+ current
(INa) density was reduced by 28% at -40 mV
(P<.0001, n=59 cells). INa
changes were even more decreased under P42 conditions, by 
52% at
-40 mV (P<.0001): from -78.7±4.6 pA/pF (P0, n=28
cells) to -37.7±3.0 pA/pF (P42, n=43 cells).
INa was significantly reduced at all
voltages ranging from -65 to -10 mV. Voltage-dependent activation and
inactivation properties, activation kinetics, and recovery from
inactivation were not altered by rapid atrial pacing; however,
inactivation kinetics were slowed. AF duration was related to mean
INa in each dog
(r2=.573, P<.001). We
conclude that rapid atrial activation significantly reduces both
conduction velocity and INa density. Since
INa is a major determinant of conduction
velocity, our data point to INa reduction as
a potentially important mechanism contributing to the substrate for AF
in this model.
Key Words: atrial fibrillation • rapid atrial pacing • Na+ current • conduction velocity
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