NF kappa B expression during cold ischemia correlates with postreperfusiongraft function

In liver transplantation, activation of NF kappa B occurs upon reperfusion, yet few data exist regarding NF kappa B activation during cold ischemia. W e hypothesized that activation of NF kappa B may initially occur during col d ischemia, prior to reperfusion, and serve as an important determinant of postreperfusion function. To test this hypothesis, serial biopsies during p orcine liver harvest were obtained immediately upon laparotomy, upon comple tion of dissection, after 45 and 120 min of cold ischemia, and 60 and 180 m in after reperfusion, Nuclear extracts were isolated for Western blot analy sis of NF kappa B, Hepatic function was assessed through bile output and so rbitol dehydrogenase (SDH) activity. NF kappa B expression was maximal at 4 5 min of cold ischemia and decreased by 120 min. The expression at 120 min of cold ischemia correlated with markers of postreperfusion function, namel y bile flow and SDH activity. During reperfusion a second distinct peak occ urred at 180 min. Increased expression of NF kappa B at 180 min of reperfus ion correlated directly with prior expression at 120 min during cold ischem ia and with increased SDH activity. These data indicate that nuclear expres sion of NF kappa B demonstrate two distinct peaks of activity, one during c old ischemia and one after reperfusion, Enhanced expression of NF kappa B d uring cold ischemia not only correlates directly with NF kappa B expression during reperfusion, but also correlates inversely with postreperfusion gra ft function. (C) 2000 Academic Press.