Intravenous AMP 579, a novel adenosine A1/A2a receptor agonist, induces a delayed protection against myocardial infarction in minipig

Abstract The aim of the study was to probe if acute administration of [1 S -[1 a ,2 b ,3 b ,4 a ( S *)]]-4-[7-[[2-(3-chloro-2-thienyl)-1-methylpropyl]amino]-3 H -imidazo[4,5- b ] pyridin-3-yl] cyclopentane carboxamide (AMP 579) could provide a delayed protection against myocardial ischemia–reperfusion injury after 24 h. Anesthetized Yucatan minipigs were given an intravenous (i.v.) loading dose (3 μg/kg) of AMP 579 in 2 min followed by a 68-min infusion (0.3 μg/kg/min) and were allowed to recover. After 24 h, the animals were subjected to an open-chest operation and the left anterior descending coronary artery was occluded for 40 min, followed by 3 h of reperfusion. Results indicated that there were no significant differences in hemodynamic parameters between vehicle- and drug-treated groups either during drug infusion or ischemia–reperfusion. Both groups had similar area at risk (24.9% for vehicle and 25.1% for AMP 579-treated). However, the infarct size was 36.5% of area at risk in vehicle group ( n =8) and 12.5% in AMP 579 group ( n =8), representing a 66% reduction of infarct size by AMP 579 ( p =0.011). This is the first report to demonstrate that in a large animal model, a hemodynamically silent, single i.v. dose of an adenosine receptor agonist can result in a delayed protection against myocardial infarction.