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Effects of inhibiting Na+/H+-exchange or angiotensin converting enzyme on atrial tachycardia-induced remodeling

2002; Oxford University Press; Volume: 54; Issue: 2 Linguagem: Inglês

10.1016/s0008-6363(01)00515-6

1755-3245

Kaori Shinagawa,

Atrial Fibrillation Management and Outcomes

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.