© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Effects of inhibiting Na+/H+-exchange or angiotensin converting enzyme on atrial tachycardia-induced remodeling
aDepartment of Medicine, University of Montreal, and Montreal Heart Institute Research Center, 5000 Belanger Street East, Montreal, Quebec, Canada H1T 1C8
bCardiopulmonary Division, Keio University School of Medicine, Tokyo, Japan
cDepartment of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
* Corresponding author. Tel.: +1-514-376-3330; fax: +1-514-376-1355 nattel{at}icm.umontreal.ca
Background: Inhibitors of the Na+/H+-exchanger (NHE1) and of angiotensin-converting enzyme (ACE) have been shown to reduce short-term (<6 h) tachycardia-induced atrial electrical remodeling. The role of NHE1 and ACE in longer-term electrical remodeling, as might occur with persistent AF, has not been studied. Methods: Dogs were subjected to atrial-tachypacing (400 bpm) for 7 days during treatment with 240 mg/day (standard clinical dose) of the NHE1 inhibitor cariporide (CariL, n=6), 1000 mg/day cariporide (CariH, n=6), 2 mg/kg/day of the ACE inhibitor enalapril (E, n=6), or no-drug controls (n=7). To ensure steady state concentrations at the onset of pacing, treatment began 3 days before the initiation of atrial tachypacing. Results were compared to those of unpaced dogs (n=9). Results: Atrial tachypacing reduced atrial effective refractory period (ERP), e.g. at a basic cycle length of 300 ms from 126±4 ms (unpaced, mean±S.E.) to 79±8 ms (no-drug controls, P<0.001). ERP abbreviation was unchanged by CariL (83±8 ms), CariH (80±7 ms), or E (76±5 ms). Atrial tachypacing increased mean duration of the longest AF episode in each dog (DAF) from 130±80 s (unpaced) similarly in all groups: 864±364 s, no-drug controls; 609±376 s, CariL; 709±353 s, CariH; 645±365 s, E (P=NS for differences among groups). Sustained AF requiring cardioversion for termination was induced in 0% of unpaced dogs vs. 33% of CariL, 33% of CariH, 33% of E, and 43% of control dogs. AF inducibility by single extrastimuli increased from 4±2% in unpaced dogs to 48±13% (P<0.01) in no-drug control dogs, an effect not changed by CariL (33±14%), CariH (35±17%) or E (48±16%). Conclusions: In contrast to short-term (several-hour) atrial tachycardia-induced remodeling, remodeling by 7-day tachycardia is not affected by NHE1 or ACE inhibition. These results support the notion that short-term atrial tachycardia remodeling involves different mechanisms from longer-term remodeling, and urges caution in extrapolating results from studies of short-term remodeling to effects in longer-term remodeling as often occurs clinically.
KEYWORDS Antiarrhythmic agents; Arrhythmia (mechanisms); ECG; Ion exchangers; Renin–angiotensin system
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