Inhibition of the Na+/H+ exchanger delays the development of rapid pacing-induced atrial contractile dysfunction

Background-Atrial mechanical stunning due to atrial fibrillation may persis t after restoration of sinus rhythm. Although the mechanism of rapid rate-r elated contractile dysfunction remains unknown, ischemia, pH changes, and c alcium overload have been postulated as potential mechanisms. We hypothesiz ed that blockade of the Na+/H+ exchanger (NHE) would alter atrial contracti le dysfunction from rapid rates. Methods and Results-Twenty-three anesthetized dogs were studied and subject ed to 5 hours of rapid right atrial pacing. Ten received an inhibitor of th e NHE, 10 received saline, and 3 received nifedipine. All animals underwent placement of 2 sonomicrometers on the left atrium, transesophageal echocar diography, and invasive hemodynamic monitoring. All measurements were made in sinus rhythm. Except for baseline and postdrug measurements, reduction i n left atrial fractional shortening was significantly less at all time poin ts in the NHEI group than in the control and nifedipine groups (P=0.05). Th e percent change from baseline of left atrial function at all time interval s as assessed by left atrial appendage contraction velocity (LAACV) was sig nificantly 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 signif icant difference in hemodynamics among the groups was between the control a nd 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 contr ol and nifedipine-treated groups.