RT Journal Article SR Electronic T1 Adenosine A2 Receptor Activation Attenuates Reperfusion Injury by Inhibiting Neutrophil Accumulation, Superoxide Generation and Coronary Endothelial Adherence JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 301 OP 309 VO 280 IS 1 A1 James E. Jordan A1 Zhi-Qing Zhao A1 Hiroki Sato A1 Spencer Taft A1 Jakob Vinten-Johansen YR 1997 UL http://jpet.aspetjournals.org/content/280/1/301.abstract AB This study tests the hypothesis that adenosine A2 receptor activation reduces reperfusion injury by inhibiting neutrophils in a canine model of ischemia and reperfusion. In 16 anesthetized, open-chest dogs, the left anterior descending coronary artery was ligated for 60 min and reperfused for 3 hr. An intracoronary infusion of either the selective adenosine A2 agonist CGS-21680 at 0.2 μg/kg/min (n = 8) or vehicle (n = 8) was started 5 min before reperfusion and discontinued after 60 min. The area at risk was comparable between vehicle-treated and CGS-21680-treated groups (39.6 ± 4.1vs. 37.1 ± 2.5% of left ventricle). Infarction size, determined with triphenyltetrazolium chloride, was smaller in the CGS-21680-treated group than in the vehicle-treated group (15.4 ± 2.9 vs. 29.8 ± 2.3% of area at risk, P < .05 vs. vehicle-treated group). CGS-21680 significantly reduced neutrophil accumulation (myeloperoxidase activity) in the nonnecrotic area at risk tissue, compared with the vehicle-treated group (2.12 ± 0.5 vs. 6.47 ± 0.6 U/g of tissue, P < .05 vs. vehicle-treated group). Inin vitro studies, CGS-21680 reduced platelet-activating factor (PAF)-activated canine neutrophil adherence to the endothelial surface of normal homologous coronary artery segments. Compared with PAF-stimulated neutrophils (188.4 ± 9.4 adhered neutrophils/mm2), CGS-21680 reduced adherence close to base-line levels (46.6 ± 5.8 adhered neutrophils/mm2) at concentrations of 10 μM (65.6 ± 8.2 adhered neutrophils/mm2, P < .05 vs.PAF-stimulated group) and 50 μM (56.6 ± 4.6 adhered neutrophils/mm2, P < .05 vs.PAF-stimulated group). Superoxide anion production (cytochromec reduction) by activated neutrophils was reduced by CGS-21680 from 33.8 ± 5.0 to 8.9 ± 3.6 nmol/5 min/5 × 106 cells (P < .05 vs. PAF-stimulated group). We conclude that specific A2 receptor stimulation with CGS-21680 at reflow reduces reperfusion injury by inhibiting neutrophil-related processes. The American Society for Pharmacology and Experimental Therapeutics