Role of the Na(+)/H(+) exchanger in short-term atrial electrophysiological remodeling

Circulation. 2000 Apr 18;101(15):1861-6. doi: 10.1161/01.cir.101.15.1861.

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.

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, 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Atrial Fibrillation / physiopathology*
  • Dogs
  • Electrophysiology
  • Glyburide / pharmacology
  • Guanidines / pharmacology
  • Myocardial Ischemia / physiopathology
  • Sodium-Hydrogen Exchangers / antagonists & inhibitors
  • Sodium-Hydrogen Exchangers / physiology*
  • Sulfones / pharmacology
  • Time Factors

Substances

  • Anti-Arrhythmia Agents
  • Guanidines
  • Sodium-Hydrogen Exchangers
  • Sulfones
  • cariporide
  • Glyburide