Fig. 1. Adora2b in ischemia-reperfusion injury. Overview of the four different experimental protocols used in this study (A ). Immunohistochemistry for the adenosine receptor A2b (Adora2b) revealed complete lack of Adora2b staining in Adora2b−/−animals, whereas wild-type (WT) animals exhibit strong Adora2b protein expression in the heart and lung (B ). The absence of the Adora2b led to IS of 64 ± 4%. ISs are presented as percentage of the area at risk (AAR). Serum troponin I concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Adora2b−/−mice had troponin I values of 110 ± 12 ng/ml, whereas WT had troponin I values of 36 ± 4 ng/ml (C ). Two- and three-dimensional structure of BAY 60-6583, a highly specific Adora2b agonist used in this study (D ). WT mice were treated with BAY 60-6583 upon reperfusion, and the ISs and troponin I values were measured. BAY 60-6583 treatment reduced IS from 54 ± 5% to 28 ± 8%. Troponin I values in the serum were reduced from 35 ± 5 to 8 ± 2 ng/ml by Adora2b agonist treatment (mean ± SD; n = 5 per group) (E ). A/T = anesthesia-thoracotomy; BMTx = bone marrow transplantation; ± BAY = with or without BAY 60-6583; cTnI = cardiac troponin I; cytokines = multiplex ELISA for cytokines; GR-1 = anti-polymorphonuclear leukocyte (PMN) antibody; H&E = hematoxylin and eosin stain; IS = infarct size.