ASSESSMENT OF HEPATIC PHAGOCYTIC-ACTIVITY BY INVIVO MICROSCOPY AFTER LIVER-TRANSPLANTATION IN THE RAT

Phagocytic activity of sinusoidal lining cells was studied in 32 livers of male Lewis rats by in vivo fluorescence microscopy with epiillumination. Normal livers (group 1, n = 8) were compared with orthotopic syngeneic liver grafts 90 min after reperfusion after a period of cold storage in University of Wisconsin solution for 17 hr (group 2, n = 10) or 24 hr (group 3, n = 14). After bolus injection of fluorescence-labeled latex particles (3 x 10(8)/kg, diameter = 1.1-mu-m), zonal distribution and kinetics of adherence of latex beads were quantified by off-line video analysis. Hepatocellular function was estimated by the rate of bile production and biliary concentrations of bile acids. In normal livers 50%, 37% and 13% of injected latex beads adhered in zones 1, 2 and 3, respectively, whereas in transplanted livers a more homogeneous distribution was found (group 2: 37%, 41%, 22%; group 3: 37%, 39%, 24%; p < 0.01 vs. controls by analysis of variance). Kinetic analysis of phagocytic activity showed no significant difference between group 1 (88% adherence of visible latex beads 3 min after injection) and group 2 (90% adherence). However, after long-term preservation in group 3, sinusoidal adherence was significantly faster (96.4% adherence; p < 0.001). Bile secretion in group 2 was lower than in controls and severely depressed in group 3 (group 1: 1.1 +/- 0.07 mu-l/min/gm liver [mean +/- S.E.M.]; group 2: 0.8 +/- 0.07; group 3: 0.1 +/- 0.04; p < 0.001) without significant changes in bile acid concentrations. Bile production correlated inversely with adherence of latex particles (p < 0.001, r2 = 0.44). We conclude that increased phagocytic activity after liver transplantation is associated with depressed hepatocellular excretory function. These results provide further evidence that activated Kupffer cells are involved in hepatic reperfusion injury after extended periods of cold ischemia.