RECEPTOR-MEDIATED CARDIOPROTECTIVE EFFECTS OF ENDOGENOUS ADENOSINE ARE EXERTED PRIMARILY DURING REPERFUSION AFTER CORONARY-OCCLUSION IN THERABBIT

Background. We hypothesized that (1) endogenous adenosine released dur ing ischemia/reperfusion reduces infarct size and preserves postischem ic 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 ran domized to six groups: group 1, saline (Vehicle) (n = 10) to allow rec eptor interaction of endogenous adenosine (Ado) during ischemia/reperf usion; group 2, Ado-receptor blockade during both ischemia and reperfu sion with intravenous 8-p-sulfophenyltheophylline (0 mg/kg) (SPTIR, n= 10); group 3, Ado-receptor blockade in multiple doses during both isch emia and reperfusion (MSPTIR, n=11); group 4, blockade during reperfus ion (SFTR, n=10); group 5, blockade during reperfusion with PD115,199 (6 mg/kg) (PDR, n=10); and group 6, blockade after 30 minutes of reper fusion (SPT30R, n = 10) to allow adenosine receptor interaction during early reperfusion. Transmural myocardial blood flow in the area at ri sk (A(r)) (15-mum radiolabeled microspheres) was reduced by 96.7% in a ll groups, from 137.9+/-15.5 to 4.5+/-1.4 mL . min-1 . 100 g-1 (P<.001 ). MSPTIR, SPTIR, and SPTR significantly attenuated reactive hyperemia at 15 minutes of reperfusion (144+/-18, 141+/-22, and 144+/-20 mL . m in-1. 100 g-1, respectively) compared with Vehicle (257+/-40 mL . min- 1. 100 g-1, P<.05). This attenuation was more pronounced in the necrot ic zone than in the nonnecrotic zone. Reactive hyperemia at 15 minutes of reperfusion in SPT30R group was comparable to the Vehicle group. A t 120 minutes of reperfusion, blood flow in A(r) was significantly les s in MSPTIR (77+/-10), SPTIR (82+/-9), and SPTR (80+/-11) compared wit h Vehicle (140+/-12) and SPT30R (105+/-24 mL . min-1 . 100 g-1). Infar ct size (by triphenyltetrazolium chloride), expressed as a percent of Ar, was largest in the multiple-dose group with blockade during both i schemia and reperfusion (MSPTIR, 51.9+/-2.3%) and was significantly in creased also in single-dose SPTIR (39.1+/-2.2%) compared with 25.7+/-1 .7% in the Vehicle group (P<.05). Ado-receptor blockade only during re perfusion was associated with 14% smaller infarct size in the SPTR gro up than the MSPTIR group (P<.05). In contrast, Ado-receptor blockade a fter 30 minutes of reperfusion (SPT30R) did not increase infarct size (27.9+/-2.2%), which was comparable to infarct size in the Vehicle gro up. Conclusions. We conclude that (1) endogenous adenosine released fr om the myocardium during ischemia/reperfusion reduces infarct size by receptor-mediated mechanisms and (2) Ado-mediated cardioprotection is most pronounced during the early phase of reperfusion.