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Mechanisms of injury in porcine livers perfused with blood of patients with fulminant hepatic failure.

Publication ,  Journal Article
Collins, BH; Chari, RS; Magee, JC; Harland, RC; Lindman, BJ; Logan, JS; Bollinger, RR; Meyers, WC; Platt, JL
Published in: Transplantation
December 15, 1994

Hyperacute rejection of renal and cardiac xenografts is initiated by the reaction of recipient natural antibodies and complement with endothelial cell antigens of the donor organ. The liver is thought to be less susceptible to this form of rejection; however, the mechanisms underlying its decreased susceptibility are not known. We investigated the organ injury occurring in porcine livers perfused with blood from 4 human subjects with fulminant hepatic failure. Nine porcine livers were perfused via an extracorporeal circuit in order to provide temporary metabolic support. Each porcine liver exhibited metabolic function, and the duration of xenoperfusion ranged from 2 to 5 hr. Histologic examination of the xenoperfused livers revealed focal hepatocellular necrosis, prominent infiltration of neutrophils, and, in 7 of 9 cases, periportal and centrilobular hemorrhage and thrombosis. Immunopathology demonstrated minimal or no human IgM and IgG along the small vessels and sinusoidal surfaces. Trace deposits of human IgM were observed along the luminal surfaces of large blood vessels in most cases. Trace deposits of C3 were noted in 2 of 9 livers; however, C4, iC3b, C5b, properdin, and the membrane attack complex were not detected. Human anti-porcine natural antibody titers decreased less than expected during the perfusions. 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 necrosis, trace deposits of IgM, no deposits of complement, and an infiltrate consisting of neutrophils; however, the neutrophil influx was less than that observed in the xenoperfused livers. To further evaluate the effects of alloperfusion, venovenous bypass was established in 2 pigs and the extracorporeal circuit was utilized to perfuse 2 porcine livers. The alloperfused porcine livers had focal hepatocellular necrosis and a minimal infiltrate of neutrophils. There were no deposits of porcine IgM, IgG, or complement components. In conclusion, although the porcine livers perfused by human blood sustained structural damage, the time course, the absence of immune deposits, and the findings of similar, albeit less severe, lesions in the alloperfused livers suggest that the pathogenesis of tissue injury in the xenoperfused livers differs from that of hyperacute rejection and may be related to the action of recipient neutrophils.

Duke Scholars

Published In

Transplantation

ISSN

0041-1337

Publication Date

December 15, 1994

Volume

58

Issue

11

Start / End Page

1162 / 1171

Location

United States

Related Subject Headings

  • Swine
  • Surgery
  • Perfusion
  • Middle Aged
  • Male
  • Liver
  • Leukocyte Count
  • Immunoglobulin M
  • Immunoglobulin G
  • Immunity, Innate
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Collins, B. H., Chari, R. S., Magee, J. C., Harland, R. C., Lindman, B. J., Logan, J. S., … Platt, J. L. (1994). Mechanisms of injury in porcine livers perfused with blood of patients with fulminant hepatic failure. Transplantation, 58(11), 1162–1171.
Collins, B. H., R. S. Chari, J. C. Magee, R. C. Harland, B. J. Lindman, J. S. Logan, R. R. Bollinger, W. C. Meyers, and J. L. Platt. “Mechanisms of injury in porcine livers perfused with blood of patients with fulminant hepatic failure.Transplantation 58, no. 11 (December 15, 1994): 1162–71.
Collins BH, Chari RS, Magee JC, Harland RC, Lindman BJ, Logan JS, et al. Mechanisms of injury in porcine livers perfused with blood of patients with fulminant hepatic failure. Transplantation. 1994 Dec 15;58(11):1162–71.
Collins, B. H., et al. “Mechanisms of injury in porcine livers perfused with blood of patients with fulminant hepatic failure.Transplantation, vol. 58, no. 11, Dec. 1994, pp. 1162–71.
Collins BH, Chari RS, Magee JC, Harland RC, Lindman BJ, Logan JS, Bollinger RR, Meyers WC, Platt JL. Mechanisms of injury in porcine livers perfused with blood of patients with fulminant hepatic failure. Transplantation. 1994 Dec 15;58(11):1162–1171.

Published In

Transplantation

ISSN

0041-1337

Publication Date

December 15, 1994

Volume

58

Issue

11

Start / End Page

1162 / 1171

Location

United States

Related Subject Headings

  • Swine
  • Surgery
  • Perfusion
  • Middle Aged
  • Male
  • Liver
  • Leukocyte Count
  • Immunoglobulin M
  • Immunoglobulin G
  • Immunity, Innate