The Role of Ischemic Preconditioning in the Recruitment of Rolling and Adherent Leukocytes in Hepatic Venules after Ischemia/Reperfusion

Abstract

Background. We have recently shown that hepatic ischemia/reperfusion (I/R) results in rolling and adherence of leukocytes in terminal hepatic venules (THV) followed by hepatic enzyme elevation and tissue destruction. The objective of this study was to determine the effect of ischemic preconditioning on the recruitment of leukocytes in THV after liver I/R.Methods. Left hepatic lobe ischemia was induced for 5 min (preconditioning) in anesthetized C57B1/6 mice followed by reperfusion for 10 min and then prolonged ischemia for 30 min. The number of rolling, saltating, and adherent leukocytes in THV was measured at 0.5, 2, 5, 12, and 24 h after reperfusion using intravital video microscopy. Matching sham groups were evaluated after 30 min of ischemia.Results. Hepatic I/R elicited significant increases in the number of rolling, saltating, and adherent leukocytes, with peak values observed at 30 min and 5 h after reperfusion. All of these responses were significantly attenuated in mice undergoing ischemic preconditioning. Rolling leukocytes in THV following I/R without preconditioning reached peak levels of 25.2 ± 1.4 leuk/2 min (leukocytes/2 min) at 30 min reperfusion and 31.4 ± 1.5 leuk/2 min at 5 h reperfusion. With ischemic preconditioning these values fell to 12.3 ± 0.9 leuk/2 min and 14.4 ± 1.0 leuk/2 min, respectively (P < 0.001). Similarly, adherent leukocytes in nonpreconditioned mice reached peak values of 4.8 ± 1.3 leuk/2 min at 30 min reperfusion and 8.3 ± 1.2 leuk/2 min at 5 h reperfusion compared with 2.0 ± 1.5 leuk/2 min and 1.6 ± 1.1 leuk/2 min in preconditioned mice, respectively (P < 0.001).Conclusion. Ischemic preconditioning attenuates the initial events leading to leukocyte-mediated hepatic destruction following I/R injury. Delineating these mechanisms may play an important role in hepatic transplantation, resection, shock, and sepsis.