Inhibitory effect of ischemic preconditioning on leukocyte participation in retinal ischemia-reperfusion injury

PURPOSE. Recent reports, have shown that ischemic preconditioning induces s trong protection against retinal damage by subsequent prolonged ischemia an d that this protection is mediated by mechanisms involving the adenosine Al receptor. This, study was designed to evaluate quantitatively the effects of ischemic preconditioning on leukocyte-mediated reperfusion injury after transient retinal ischemia. and to define the role of the adenosine Al rece ptor in these effects. METHODS. Transient retinal ischemia was induced in male rats by temporary l igation of the optic nerve. Ischemic preconditioning. (5 minutes of ischemi a) was induced 24 hours before 60 minutes of ischemia. The adenosine Al rec eptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was administere d intramuscularly immediately after ischemic preconditioning. Leukocyte beh avior in the retina after 60 minutes of ischemia was evaluated in vivo with acridine orange digital fluorography. RESULTS. Ischemic preconditioning inhibited leukocyte rolling. The maximum number of rolling leukocytes was reduced to 3.0% at 12 hours after reperfus ion (P < 0.01). Subsequent leukocyte accumulation was also decreased with i schemic preconditioning. The maximum number of accumulated leukocytes was r educed to 22.6% at 24 hours after reperfusion (P < 0.01). These inhibitory effects were suppressed by administration of DPCPX (P < 0.0001). The number s of rolling leukocytes at 12 hours after reperfusion and accumulated leuko cytes at 24 hours after reperfusion were 102.7% (NS) and 83.4% (P < 0.01), respectively, compared with the number without ischemic preconditioning. CONCLUSION. The present study demonstrates the inhibitory effects of ischem ic preconditioning on leukocyte rolling and subsequent leukocyte accumulati on during retinal ischemia-reperfusion injury. Furthermore, the adenosine A l receptor may play an important role in these inhibitory effects.