Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit. Circulation

Background. We hypothesized that (1) endogenous adenosine released during ischemia/reperfusion reduces infarct size and preserves postischemic myocardial blood flow by receptor-mediated mechanisms and (2) this cardioprotection is exerted predominantly during reperfusion. Methods and Results. Sixty-one anesthetized open-chest rabbits subjected to 30 minutes of coronary occlusion and 120 minutes of reperfusion were randomized to six groups: group 1, saline (Vehicle) (n = 10) to allow receptor interaction of endogenous adenosine (Ado) during ischemia/reperfusion; group 2, Ado-receptor blockade during both ischemia and reperfusion with intravenous 8-p-sulfophenyltheophyl-line (10 mg/kg) (SPTIR, n=10); group 3, Ado-receptor blockade in multiple doses during both ischemia and reperfusion (MSPTIR, n=11); group 4, blockade during reperfusion (SPTR, n=10); group 5, blockade during reperfusion with PD115,199 (6 mg/kg) (PDR, n=10); and group 6, blockade after 30 minutes of reperfusion (SPT3OR, n = 10) to allow adenosine receptor interaction during early reperfusion. Transmural myocardial blood flow in the area at risk (Ar) (15-jm radiolabeled microspheres) was reduced by 96.7 % in all groups, from 137.9±15.5 to 4.5±1.4 mL min'l 100 g ` (P<.001). MSPTIR, SPTIR, and SPTR significantly attenuated reactive hyperemia at 15 minutes of reperfusion (144±18, 141±22, and 144±20 mL * min'l 100 g-', respectively) compared with Vehicle (257±40 mL * min'l 10