Oral GAP-134 did not significantly reduce AF inducibility in all paced dogs, but reduced AF induction from 100% to 40% (P<0.05) in a subgroup with less atrial mechanical remodeling.
RCT (n=32)
randomly assigned
Does oral GAP-134 reduce AF inducibility and maintenance in a dog model of pacing-induced atrial cardiomyopathy?
The gap junction conduction-enhancing peptide GAP-134 may attenuate AF vulnerability in dogs with pacing-induced atrial cardiomyopathy, specifically in those with less severe atrial mechanical remodeling.
Background— Abnormal intercellular communication caused by connexin dysfunction may contribute to atrial fibrillation (AF). The present study assessed the effect of the gap junction conduction–enhancing antiarrhythmic peptide GAP-134 on AF inducibility and maintenance in a dog model of atrial cardiomyopathy. Methods and Results— Twenty-four dogs subject to simultaneous atrioventricular pacing (220 bpm for 14 days) were randomly assigned to placebo treatment (PACED-CTRL; 12 dogs) or oral GAP-134 (2.9 mg/kg BID; PACED-GAP-134; 12 dogs) starting on day 0. UNPACED-CTRL (4 dogs) and UNPACED-GAP-134 (4 dogs) served as additional control groups. Change in left atrial (LA) systolic area from baseline to 14 days was calculated using transoesophageal echocardiography. At 14 days, animals underwent an open-chest electrophysiological study. PACED-CTRL dogs (versus UNPACED-CTRL) had a shorter estimated LA wavelength (8.0�1.4 versus 24.4�2.5 cm, P <0.05) and a greater AF vulnerability (mean AF duration, 1588�329 versus 25�34 seconds, P <0.05). Oral GAP-134 had no effect on AF vulnerability in UNPACED dogs. Compared with PACED-CTRL dogs, PACED-GAP-134 dogs had a longer estimated LA wavelength (10.2�2.8 versus 8.0�1.4 cm, respectively, P <0.05). Oral GAP-134 did not significantly reduce AF inducibility or maintenance in the entire group of 24 PACED dogs; in a subgroup of dogs (n=11) with less than 100% increase in LA systolic area, oral GAP-134 reduced AF induction from 100% to 40% and mean AF duration from 1737�120 to 615�280 seconds ( P <0.05). Conclusions— Oral GAP-134 reduces pacing-induced decrease in LA wavelength and appears to attenuate AF vulnerability in dogs with less atrial mechanical remodeling. Gap junction modulation may affect AF in some circumstances.
Laurent et al. (Sat,) conducted a rct in Experimental Atrial Fibrillation (n=32). GAP-134 vs. Placebo was evaluated on AF inducibility or maintenance. Oral GAP-134 did not significantly reduce AF inducibility in all paced dogs, but reduced AF induction from 100% to 40% (P<0.05) in a subgroup with less atrial mechanical remodeling.
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