(Circulation. 2000;101:1861.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Role of the Na+/H+ Exchanger in Short-Term Atrial Electrophysiological Remodeling
From the Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis.
Correspondence to Jeffrey Olgin, MD, Krannert Institute of Cardiology, Indiana University School of Medicine, 1111 W 10th St, Indianapolis, IN 46202. E-mail jolgin{at}iupui.edu
Background—The pathophysiology underlying electrophysiological remodeling (ER) from rapid atrial rates is unknown. We tested the hypothesis that activation of the Na+/H+ exchanger (NHE) by ischemia contributes to ER.
Methods and Results—Twenty-eight dogs were studied under autonomic blockade. In 15 closed-chest dogs, atrial fibrillation was simulated by right atrial pacing at 600 bpm over 5 hours. Of these, 9 (pace/NHEI) received HOE642, a selective inhibitor of the NHE, and 6 (pace/control) received saline. In pace/controls, atrial effective refractory period (AERP) at a drive cycle length (DCL) of 400 ms shortened from 143±7 to 118±5 ms (1 hour) and to 122±17 ms (5 hours). Shortening of AERP was prevented in the pace/NHEI group (P=0.02 compared with pace/controls). At baseline in all 15 dogs, pacing at shorter DCL resulted in shortening of AERP (physiological rate adaptation), which was lost at 5 hours in pace/controls. In pace/NHEI animals, rate adaptation was maintained despite 5 hours of pacing (P=0.02). In 13 other open-chest dogs, right atrial ERP was determined before and after occlusion of the right coronary artery. Five received HOE642 (ischemia/NHEI), 5 saline (ischemia/control), and 3 intravenous glibenclamide. In ischemia/controls, AERP400 decreased (156±30 to 130±32 ms). Shortening of AERP was not prevented by glibenclamide (180±20 to 153±33 ms) but was prevented in ischemia/NHEI dogs (169±12 to 184±19 ms, P=0.001 compared with ischemia/controls and ischemia/glibenclamide). Rate adaptation was lost in ischemia/controls and preserved in ischemia/NHEI dogs (P=0.02).
Conclusions—Activation of the NHE is one mechanism underlying short-term ER.
Key Words: fibrillation • electrophysiology • remodeling • sodium • calcium • arrhythmia • ischemia • glibenclamide
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