TIME-COURSE OF LEUKOCYTE ADHESION TO ENDOTHELIUM IN ISCHEMIA-REPERFUSION

Adhesion of leukocytes (L) to microvascular endothelium (E) is a requi red step in the L-E interaction leading to tissue injury in ischemia-r eperfusion. To assess the optimum period for therapy aimed at ameliora ting negative effects of this required step, we investigated the time course of L-E adhesion in the hamster cheek pouch using 2 hr of ischem ia and 1 hr of reperfusion in our model of I-R injury (Am. J. Physiol. 261: 1626, 1991). Leukocytes adhering (stationary for greater than or equal to 30 sec) to postcapillary venules (15-30 mu m in diameter) we re counted after labeling with acridine orange. Prior to the induction of ischemia, there were no significant differences in the number of a dherent leukocytes in each area chosen for study (1.9 +/- 0.6 vs 2.0 /- 0.3; mean number of leukocytes/100-mu m vessel length +/- SD). Afte r 10 and 20 min of reperfusion there was no significant difference in leukocyte adhesion in the ischemic area relative to the control (2.7 /- 0.5 vs 2.8 +/- 0.8, and 5.3 +/- 2.8 vs 2.4 +/- 0.6, respectively), Leukocyte adherence increased significantly after 30 min of reperfusio n and remained elevated at 1 hr of reperfusion in the postischemic are a relative to the nonischemic control area (7.8 +/- 1.3 vs 3.6 +/- 0.6 , and 8.3 +/- 0.8 vs 4.1 +/- 0.6, respectively; P < 0.01). Leukocyte a dhesion in the postischemic area after 30 min reperfusion was not sign ificantly different from the adhesion at the end of 1 hr reperfusion. These data suggest that (1) peak leukocyte adhesion occurs after 30 mi n of normal reperfusion and (2) postischemic therapeutic intervention may be most beneficial when instituted within this early time period. (C) 1996 Academic Press, Inc.