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

被引:85
作者
Jayachandran, JV [1 ]
Zipes, DP [1 ]
Weksler, J [1 ]
Olgin, JE [1 ]
机构
[1] Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA
关键词
fibrillation; electrophysiology; remodeling; sodium; calcium; arrhythmia; ischemia; glibenclamide;
D O I
10.1161/01.CIR.101.15.1861
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1861 / 1866
页数:6
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