title: Role of the Na(+)/H(+) exchanger in short-term atrial electrophysiological remodeling.
abstract: 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.
  
  
  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, AERP(400) 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.
authors.affiliation: Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Jayachandran
authors.forename: D P
authors.initials: DP
authors.lastname: Zipes
authors.forename: J
authors.initials: J
authors.lastname: Weksler
authors.forename: J E
authors.initials: JE
authors.lastname: Olgin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000503:physiopathology*; D004285:Dogs; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000503:physiopathology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D005905:Glyburide