Reduction in myocardial infarct size at 48 hours after brief intravenous infusion of ATL-146e, a highly selective adenosine A^sub 2A^ receptor agonist

• Published in: American journal of physiology. Heart and circulatory physiology 2009-08, Vol.297 (2), p.H637
• Main Authors: Patel, Rajan A G, Glover, David K, Broisat, Alexis, Kabul, Hasan K, Ruiz, Mirta, Goodman, N Craig, Kramer, Christopher M, Meerdink, Denis J, Linden, Joel, Beller, George A
• Format: Article
• Language: English
• Subjects: Adenosine; Blood vessels; Dogs; Heart; Heart attacks; Studies; T cell receptors
• ISSN: 0363-6135; 1522-1539

This study was undertaken to determine whether the myocardial infarct-sparing effect of ATL-146e, a selective adenosine ... receptor agonist, persists without a rebound effect for at least 48 h and to determine the optimal duration of ATL-146e treatment in anesthetized dogs. Reperfusion injury after myocardial infarction (MI) is associated with inflammation lasting 24 - 48 h that contributes to ongoing myocyte injury. We previously showed that an ATL-146e infusion, starting just before reperfusion, decreased inflammation and infarct size in dogs examined 2 h after MI without increasing coronary blood flow. In the present study, adult dogs underwent 90 min of left anterior descending coronary artery occlusion. Thirty minutes before reperfusion, ATL-146e (0.01 ...g-kg...-min...-; n = 21) or vehicle (n = 12) was intravenously infused and continued for 2.5 h (protocol 1) or 24 h (protocol 2). At 48 h after reperfusion hearts were excised and assessed for histological risk area and infarct size. Infarct size based on triphenyltetrazolium chloride (TTC) staining as a percentage of risk area was significantly smaller in ATL-146e-treated vs. control dogs (16.7 ± 3.7% vs. 33.3 ± 6.2%, P < 0.05; protocol 1). ATL-146e reduced neutrophil accumulation into infarcted myocardium of ATL-146e-treated vs. control dogs (30 ± 7 vs. 88 ± 16 cells/high-power field, P < 0.002). ATL-146e infusion for 24 h (protocol 2) conferred no significant additional infarct size reduction compared with 2.5 h of infusion. A 2.5-h ATL-146e infusion initiated 30 min before reperfusion results in marked, persistent (48 h) reduction in infarct size as a percentage of risk area in dogs with a reduction in infarct zone neutrophil infiltration. No significant further benefit was seen with a 24-h infusion. (ProQuest: ... denotes formulae/symbols omitted.)