Humoral injury in porcine livers perfused with human whole blood.

Abstract

We investigated the influence of humoral injury during xenoperfusion of porcine livers by human blood. The porcine livers were perfused under physiological conditions for 9 hr. The perfusates consisted of porcine whole blood in group 1, human whole blood in group 2, and human whole blood with soluble complement receptor type 1 (300 microg/ml) in group 3. Liver enzyme release and serum hemoglobin in group 2 increased significantly after 3 hr of xenoperfusion, compared with those in group 1 and group 3 (P<0.05). Severe histological damage with minimal cellular infiltration was observed in group 2 after 6 hr of xenoperfusion, but was present only at trace levels in group 1 and group 3. In group 2, von Willebrand factor, a possible target of natural antibodies, was induced on sinusoidal endothelial cells after 3 hr of xenoperfusion, correlating with diffuse deposition of human IgM and membrane attack complex. In group 3, von Willebrand factor, human IgM, and membrane attack complex staining in the intralobular region were present at trace levels. In group 3, the indocyanine green removal capacity, representing hepatocyte function, was significantly higher than in group 2 (P<0.05). Based on these results, we suggest that humoral injury is a major cause of liver damage during liver xenoperfusion. The pattern of humoral injury in xenoperfused livers may be attributed to anatomical features of the liver and unique responses of sinusoidal endothelial cells to xenoperfusion.