GAP-134 ([2S,4R]-1-[2-aminoacetyl]4-benzamidopyrrolidine-2-carboxylic acid) prevents spontaneous ventricular arrhythmias and reduces infarct size during myocardial ischemia/reperfusion injury in open-chest dogs.

The antiarrhythmic dipeptide, GAP-134, ([2S,4R]-1-[2-aminoacetyl]-4-benzamido-pyrrolidine-2-carboxylic acid) was evaluated in canine ischemia/reperfusion model. In dogs subjected to 60-minute ischemia and 4-hour reperfusion, GAP-134 was administered 10 minutes before reperfusion as a bolus + intravenous (IV) infusion. The doses administered were 0.25 mu g/kg bolus + 0.19 mu g/kg per hour infusion; 2.5 mu g/kg + 1.9 mu g/kg per hour; 25 mu g/kg + 19 mu g/kg per hour; 75 mu g/kg + 57 mu g/kg per hour. Ventricular ectopy was quantified during reperfusion, including premature ventricular contractions (PVC) and ventricular tachycardia (m. Total incidence of VT was reduced significantly with the 2 highest doses of GAP-134 (1.7 +/- 0.8; 2.2 +/- 1.4 events; P < .05) compared to controls (23.0 +/- 6.1). Total PVCs were reduced significantly from 11.1 +/- 1.6% in control animals to 2.0% +/- 0.7% and 1.8% +/- 0.8% after the 2 highest doses of GAP-134. Infarct size, expressed as percentage of left ventricle, was reduced significantly from 19.0% +/- 3.5% in controls to 7.9% +/- 1.5% and 7.1% +/- 0.8% (P < .05) at the 2 highest doses of GAP-134. GAP-134 is an effective antiarrhythmic agent with potential to reduce ischemia/reperfusion injury.