MECHANISMS OF INJURY IN PORCINE LIVERS PERFUSED WITH BLOOD OF PATIENTS WITH FULMINANT HEPATIC-FAILURE

Hyperacute rejection of renal and cardiac xenografts is initiated by t he reaction of recipient natural antibodies and complement with endoth elial cell antigens of the donor organ. The liver is thought to be les s susceptible to this form of rejection; however, the mechanisms under lying its decreased susceptibility are not known. We investigated the organ injury occurring in porcine livers perfused with blood from 4 hu man subjects with fulminant hepatic failure. Nine porcine livers were perfused via an extracorporeal circuit in order to provide temporary m etabolic support. Each porcine liver exhibited metabolic function, and the duration of xenoperfusion ranged from 2 to 5 hr. Histologic exami nation of the xenoperfused livers revealed focal hepatocellular necros is, prominent infiltration of neutrophils, and, in 7 of 9 cases, perip ortal and centrilobular hemorrhage and thrombosis. Immunopathology dem onstrated minimal or no human IgM and IgG along the small vessels and sinusoidal surfaces. Trace deposits of human IgM were observed along t he luminal surfaces of large blood vessels in most cases. Trace deposi ts of C3 were noted in 2 of 9 livers; however, C4, iC3b, C5b, properdi n, and the membrane attack complex were not detected. Human anti-porci ne natural antibody titers decreased less than expected during the per fusions. Serum CH50, C3, and C4 levels were low before each procedure and decreased slightly with perfusion. One patient perfused 2 porcine livers and a human liver. The human liver had focal hepatocellular nec rosis, trace deposits of IgM, no deposits of complement, and an infilt rate consisting of neutrophils; however, the neutrophil influx was les s than that observed in the xenoperfused livers. To further evaluate t he effects of alloperfusion, venovenous bypass was established in 2 pi gs and the extracorporeal circuit was utilized to perfuse 2 porcine li vers. The alloperfused porcine livers had focal hepatocellular necrosi s and a minimal infiltrate of neutrophils. There were no deposits of p orcine IgM, IgG, or complement components. In conclusion, although the porcine livers perfused by human blood sustained structural damage, t he time course, the absence of immune deposits, and the findings of si milar, albeit less severe, lesions in the alloperfused livers suggest that the pathogenesis of tissue injury in the xenoperfused livers diff ers from that of hyperacute rejection and may be related to the action of recipient neutrophils.