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.

Abstract

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 microg/kg bolus + 0.19 microg/kg per hour infusion; 2.5 microg/kg + 1.9 microg/kg per hour; 25 mg/kg + 19 mg/kg per hour; 75 mg/kg + 57 mg/kg per hour. Ventricular ectopy was quantified during reperfusion, including premature ventricular contractions (PVC) and ventricular tachycardia (VT). 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.

• Authors: James K Hennan, Robert E Swillo, Gwen A Morgan, Eric I Rossman, Joel Kantrowitz, John Butera, Jorgen S Petersen, Stephen J Gardell, George P Vlasuk
• Journal: Journal of cardiovascular pharmacology and therapeutics (J Cardiovasc Pharmacol Ther) Vol. 14 Issue 3 Pg. 207-14 (Sep 2009) ISSN: 1074-2484 [Print] United States
• PMID: 19721133 (Publication Type: Journal Article)

Chemical References

• 1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid
• Anti-Arrhythmia Agents
• Benzamides
• Proline

Topics

• Animals
• Anti-Arrhythmia Agents (administration & dosage, pharmacology)
• Benzamides (administration & dosage, pharmacology)
• Coronary Circulation (drug effects)
• Disease Models, Animal
• Dogs
• Dose-Response Relationship, Drug
• Infusions, Intravenous
• Myocardial Infarction (etiology, pathology, physiopathology, prevention & control)
• Myocardial Reperfusion Injury (complications, drug therapy, pathology, physiopathology)
• Myocardium (pathology)
• Proline (administration & dosage, analogs & derivatives, pharmacology)
• Tachycardia, Ventricular (etiology, pathology, physiopathology, prevention & control)
• Time Factors
• Ventricular Premature Complexes (etiology, pathology, physiopathology, prevention & control)