Background:
Abnormal intercellular communication caused by connexin dysfunction may promote atrial fibrillation (AF).
Objective:
To assess the effect of the gap junction conduction-enhancing antiarrhythmic peptide GAP-134 on AF inducibility and maintenance in a new dog model of atrial cardiomyopathy.
Methods and Results:
Twenty four dogs underwent simultaneous atrioventricular pacing (2 weeks at 220 bpm, atrioventricular delay 0 ms), and were randomly assigned to placebo treatment (PACED-PLACEBO; 12 dogs) or oral GAP-134 (PACED-GAP 134; 12 dogs) (starting at day 0). Percent change in left atrial systolic area (Δ% LASA) from baseline to 2 weeks was calculated using trans-esophageal echocardiography. At 2 weeks, animals underwent an open chest electrophysiological study; conduction velocity (CV) when pacing at 150ms cycle length (CL), effective refractory periods (ERP) and AF vulnerability were measured. The mean plasma concentration of GAP-134 was 557 ± 239 nmol/L. GAP-134 increased CV (395.1 ± 63.2 vs 307.8 ± 54.6 mm/s, p<0.01), and shortened ERP at 200ms CL (104.0 ± 8.6 vs 112.8 ± 11.5 ms, P<0.05). GAP-134 significantly reduced AF inducibility [% burst attempts inducing AF] and maintenance [mean AF duration, number of episodes >10min] in dogs with less than 100% ΔLASA (n=5). In dogs with more structural remodeling (ΔLASA ≥100%, n=7), CV increased but AF inducibility was unaffected.
Conclusions:
Oral GAP-134 prevents CV slowing in a dog model of atrial cardiomyopathy, but attenuates AF inducibility and maintenance only in dogs with less mechanical remodeling.
GW28-e0789 Trimetazidine decreases inducibility and duration of atrial fibrillation in a dog model of congestive heart failure
