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

Abstract

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-imida zo[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 microg/kg) of AMP 579 in 2 min followed by a 68-min infusion (0.3 microg/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.

• Authors: H Meng, M McVey, M Perrone, K L Clark
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 387 Issue 1 Pg. 101-5 (Jan 03 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10633167 (Publication Type: Journal Article)

Chemical References

• 4-(7-((2-3-chloro-2-thienyl)-1-methyl-propylamino)-3H-imidazo(4,5-b)pyridyl-3-yl)cyclopentane carboxamide
• Imidazoles
• Protective Agents
• Purinergic P1 Receptor Agonists
• Pyridines

Topics

• Animals
• Blood Pressure (drug effects)
• Female
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Imidazoles (pharmacology)
• Infusions, Intravenous
• Myocardial Infarction (etiology, pathology, prevention & control)
• Myocardial Reperfusion Injury (complications, physiopathology, prevention & control)
• Protective Agents (pharmacology)
• Purinergic P1 Receptor Agonists
• Pyridines (pharmacology)
• Swine
• Swine, Miniature
• Time Factors
• Ventricular Fibrillation (etiology, physiopathology)