Complement activation induced by ischemia-reperfusion in humans: a study in patients undergoing partial hepatectomy

Background/Aim: Activation of the complement system is induced by ischemia- reperfusion (IIR) in animal models. Whether I/R also induces complement act ivation in humans is not known. Here, we investigated complement activation in patients undergoing major liver resection, Methods: In 11 of 17 patients, the hepatoduodenal ligament was clamped, mak ing the liver transiently ischemic (HEMI+; mean ischemia time, 42+/-18 min) ; 6 patients were operated without clamping (HEMI-). Activation at plasma l evel (circulating activation products) was studied in blood samples collect ed prior to surgery and 5, 24 and 48 h thereafter. Parameters analyzed were C4b/c and C3b/c, C4d and C3d, C3a, as well as complexes between complement and C-reactive protein (CRP), which reflect CRP-induced complement activat ion. Activation at tissue level (C3 and C4 fixation) was studied in liver b iopsies obtained before and after resection, Results: In plasma, post-operative levels of C4b/c and C3b/c were not diffe rent from baseline levels in both groups. Mean plasma levels of C4b/c and C 3b/c were significantly decreased at 24 h post-surgery in the HEMI+ group ( p=0.02 and p=0.07), At the same time, levels of C4d-CRP and C3d-CRP were si gnificantly increased (p<0.01 for both parameters). At tissue level, activa ted complement fragments were observed intracellularly in some pericentral hepatocytes. In I/R livers, large numbers of hepatocytes were positively st ained for an complement activation products. Conclusions: Our data show that in situ complement activation via the class ical route occurred during liver resection and that ischemia and/or reperfu sion may have contributed to activation. Levels of complement activation pr oducts in the circulation were low, showing that transient ischemia had no severe influence on systemic complement activation, suggesting a locally co ntained response.