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

J. Vijay Jayachandran, Douglas P. Zipes, Juan Weksler, Jeffrey E. Olgin

Research output: Contribution to journalArticle

73 Scopus citations

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, 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.

Original languageEnglish (US)
Pages (from-to)1861-1866
Number of pages6
JournalCirculation
Volume101
Issue number15
DOIs
StatePublished - Apr 18 2000

Keywords

  • Arrhythmia
  • Calcium
  • Electrophysiology
  • Fibrillation
  • Glibenclamide
  • Ischemia
  • Remodeling
  • Sodium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Jayachandran, J. V., Zipes, D. P., Weksler, J., & Olgin, J. E. (2000). Role of the Na+/H+ exchanger in short-term atrial electrophysiological remodeling. Circulation, 101(15), 1861-1866. https://doi.org/10.1161/01.CIR.101.15.1861