Intravenous AMP 579, a novel adenosine A(1)/A(2a) receptor agonist, induces a delayed protection against myocardial infarction in minipig

The aim of the study was to probe if acute administration of [1S-[1a,2b,3b, 4a(S*)]]-4-[7-[[2-(3-chloro-2-thienyl)-1-methylpropyl]amino]-3H-imidazo[4,5 -b] pyridin-3-yl] cyclopentane carboxamide (AMP 579) could provide a delaye d protection against myocardial ischemia-reperfusion injury after 24 h. Ane sthetized Yucatan minipigs were given an intravenous (i.v.) loading dose (3 mu g/kg) of AMP 579 in 3 min followed by a 68-min infusion (0.3 mu g/kg/mi n) and were allowed to recover. After 24 h, the animals were subjected to a n open-chest operation and the left anterior descending coronary artery was occluded for 40 min, followed by 3 h of reperfusion. Results indicated tha t there were no significant differences in hemodynamic parameters between v ehicle- and drug-treated groups either during drug infusion or ischemia-rep erfusion. 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 re port 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. (C) 2000 Elsevier Science B.V. Al l rights reserved.