ADENOSINE INHIBITION OF NEUTROPHIL DAMAGE DURING REPERFUSION DOES NOTINVOLVE K-ATP-CHANNEL ACTIVATION

This study tests the hypothesis that cardioprotection exerted by adeno sine A(2)-receptor activation and neutrophil-related events involves s timulation of ATP-sensitive potassium (K-ATP) channels on neutrophils during reperfusion. The adenosine Ag agonist CGS-21680 (CGS) inhibited superoxide radical generation from isolated rabbit polymorphonuclear neutrophils (PMNs) in a dose-dependent manner from 17.7 +/- 2.1 to 7.4 +/- 1.3 nmol/5 x 10(6) PMNs (P < 0.05). Pinacidil, a K-ATP-channel op ener, partially inhibited superoxide radical production, which was com pletely reversed by glibenclamide (Glib). Incremental doses of Glib in combination with CGS (1 mu M) did not alter CGS-induced inhibition of superoxide radical generation. CGS significantly reduced PMN adherenc e to the endothelial surface of aortic segments in a dose-dependent ma nner from 189 +/- 8 to 50 +/- 6 PMNs/mm(2) (P < 0.05), which was also not altered by incremental doses of Glib. Infusion of CGS (0.025 mg/kg ) before reperfusion reduced infarct size from 29 +/- 2% in the Vehicl e group to 15 +/- 1% in rabbits undergoing 30 min of ischemia and 120 min of reperfusion (P < 0.05). Glib (0.3 mg/kg) did not change the inf arct size (28 +/- 2%) vs. the Vehicle group and did not attenuate infa rct size reduction by CGS (16 +/- 1%). Glib did not change blood gluco se levels. Cardiac myeloperoxidase activity was decreased in the ische mic tissue of the CGS group (0.15 +/- 0.03 U/100 mg tissue) compared w ith the Vehicle group (0.37 +/- 0.05 U/100 mg tissue; P < 0.05). We co nclude that adenosine A(2) activation before reperfusion partially red uces infarct size by inhibiting neutrophil activity and that this effe ct does not involve K-ATP-channel stimulation.