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(Circulation. 2001;103:762.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Inhibition of the Na⁺/H⁺ Exchanger Delays the Development of Rapid Pacing–Induced Atrial Contractile Dysfunction

Gregory T. Altemose, MD; Douglas P. Zipes, MD; Juan Weksler, MD; John M. Miller, MD; Jeffrey E. Olgin, MD

From the Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis.

Correspondence to Jeffrey E. 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—Atrial mechanical stunning due to atrial fibrillation may persist after restoration of sinus rhythm. Although the mechanism of rapid rate–related contractile dysfunction remains unknown, ischemia, pH changes, and calcium overload have been postulated as potential mechanisms. We hypothesized that blockade of the Na⁺/H⁺ exchanger (NHE) would alter atrial contractile dysfunction from rapid rates.

Methods and Results—Twenty-three anesthetized dogs were studied and subjected to 5 hours of rapid right atrial pacing. Ten received an inhibitor of the NHE, 10 received saline, and 3 received nifedipine. All animals underwent placement of 2 sonomicrometers on the left atrium, transesophageal echocardiography, and invasive hemodynamic monitoring. All measurements were made in sinus rhythm. Except for baseline and postdrug measurements, reduction in left atrial fractional shortening was significantly less at all time points in the NHEI group than in the control and nifedipine groups (P=0.05). The percent change from baseline of left atrial function at all time intervals as assessed by left atrial appendage contraction velocity (LAACV) was significantly less in the NHEI group than in the control (P=0.05) group. LAACV was significantly preserved at all time intervals (except 300 minutes) in the NHEI group compared with the nifedipine group (P=0.05). The only significant difference in hemodynamics among the groups was between the control and the nifedipine groups at 30 minutes after drug (P=0.05).

Conclusions—Treatment with HOE642 significantly blunts the decline in left atrial mechanical function from rapid atrial rates compared with both control and nifedipine-treated groups.

Key Words: fibrillation • contractility • sodium • arrhythmias

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