Adenosine inhibition of neutrophil damage during reperfusion does not involve KATP-channel activation.

This study tests the hypothesis that cardioprotection exerted by adenosine A2-receptor activation and neutrophil-related events involves stimulation of ATP-sensitive potassium (KATP) channels on neutrophils during reperfusion. The adenosine A2 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 × 106 PMNs ( P < 0.05). Pinacidil, a KATP-channel opener, partially inhibited superoxide radical production, which was completely reversed by glibenclamide (Glib). Incremental doses of Glib in combination with CGS (1 μM) did not alter CGS-induced inhibition of superoxide radical generation. CGS significantly reduced PMN adherence to the endothelial surface of aortic segments in a dose-dependent manner from 189 ± 8 to 50 ± 6 PMNs/mm2( 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 Vehicle 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 infarct size (28 ± 2%) vs. the Vehicle group and did not attenuate infarct size reduction by CGS (16 ± 1%). Glib did not change blood glucose levels. Cardiac myeloperoxidase activity was decreased in the ischemic tissue of the CGS group (0.15 ± 0.03 U/100 mg tissue) compared with the Vehicle group (0.37 ± 0.05 U/100 mg tissue; P < 0.05). We conclude that adenosine A2 activation before reperfusion partially reduces infarct size by inhibiting neutrophil activity and that this effect does not involve KATP-channel stimulation.