Experimental discordant hepatic xenotransplantation in the recipient with liver failure: Implications for clinical bridging trials

A. Joseph Tector, Jonathan A. Fridell, Phillip Ruiz, Reena J. Khurana, G. Jensen, Anton Mak, Doris Greinke, Julie Salazar, William Stevenson, Peter Metrakos, Jean Tchervenkov

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Background: Clinical xenotransplantation might start with bridge-to- bridge trials. Situations where hyperacute rejection is avoided would provide opportunities for the initiation of bridging trials. Patients with liver failure have a diminished capacity to initiate antibody and complement- induced injury of xenogeneic endothelium. Hyperacute rejection of a liver xenograft manifests as a coagulopathy. We examined the ability of a recipient with liver failure to hyperacutely reject a liver xenograft in the dog-to-pig model in the immediate postoperative period. Study Design: Liver failure in pigs was induced with galactosamine. Canine livers were transplanted into pigs with liver failure and into healthy pigs. The postoperative course was monitored for 1 hour for histologic changes in the xenograft, changes in platelet counts, and whole blood dotting with Sonoclot analysis. In vitro assays with pig serum and canine hepatic sinusoidal endothelial cells were used to assess the effect of liver failure on serum cytotoxicity and xenoreactive antibody levels. Results: All untreated pig recipients of liver xenografts died from a coagulopathy. Recipients with liver failure manifested no signs of coagulopathy, and had minimal change in platelet counts or Sonodot (Sienco Inc., Morrison, CO) tracings. Liver xenograft biopsies from recipients with liver failure showed no evidence of the tissue injury that characterized the biopsies of control recipients. Serum from. pigs was less cytotoxic to the canine hepatic sinusoidal endothelium after induction of liver failure. The xenoreactive antibody levels and repertoire were similar in the pig serum before and after liver failure was induced. CH50 (total complement) levels were diminished in pigs after the induction of liver failure. Conclusions: Liver xenotransplantation used in bridging trials in recipients with liver failure might not face the barrier of hyperacute rejection. (C) 2000 American College of Surgeons.

Original languageEnglish (US)
Pages (from-to)54-64
Number of pages11
JournalJournal of the American College of Surgeons
Volume191
Issue number1
DOIs
StatePublished - Jul 2000

ASJC Scopus subject areas

  • Surgery

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    Tector, A. J., Fridell, J. A., Ruiz, P., Khurana, R. J., Jensen, G., Mak, A., Greinke, D., Salazar, J., Stevenson, W., Metrakos, P., & Tchervenkov, J. (2000). Experimental discordant hepatic xenotransplantation in the recipient with liver failure: Implications for clinical bridging trials. Journal of the American College of Surgeons, 191(1), 54-64. https://doi.org/10.1016/S1072-7515(00)00293-3