Prolonged function of extracorporeal hDAF transgenic pig livers perfused with human blood.
BACKGROUND
The development of genetically modified pigs has renewed interest in the use of porcine liver perfusion in the treatment of acute liver failure.


METHODS
A previously developed model of extracorporeal perfusion has been used to test the function of porcine livers transgenic for human decay accelerating factor when perfused with fresh, whole, human blood. Three experimental groups were studied: alloperfusions (normal pig livers perfused with pig blood) and xenoperfusions of both unmodified and transgenic pig livers with human blood. All livers were perfused for up to 72 hr.


RESULTS
Alloperfusion resulted in the maintenance of good function and histological structure. Stable hemodynamic, synthetic, and metabolic parameters were demonstrated in both unmodified and transgenic liver xenoperfusions; hyperacute rejection was not seen. In both groups, however, the measured parameters of liver function deteriorated toward the end of the 72 hr perfusion period; deterioration was more marked in the nontransgenic group. Xenoperfusions were characterized by a progressive and marked decrease in hematocrit of the circulating blood. Histologically, patchy necrosis was noted in both groups and more retained erythrocytes were seen in the sinusoids of nontransgenic livers, but no other consistent differences were apparent.


CONCLUSIONS
These studies have demonstrated that porcine liver xenoperfusions can be performed for prolonged periods while maintaining good liver function. The use of organs from animals transgenic for a human complement regulator protein confers improvement in some measures of liver function. This preclinical model provides evidence that extracorporeal liver xenoperfusion may be effective in temporary liver support for patients in acute liver failure.
Rees
Michael A
MA
Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 2QQ United Kingdom. mrees@mco.edu
Butler
Andrew J
AJ
Chavez-Cartaya
Gilda
G
Wight
Derek G D
DG
Casey
Neil D
ND
Alexander
Graeme
G
Khuder
Sadik A
SA
White
David J G
DJ
Friend
Peter J
PJ
D000818:Animals; D030801:Animals, Genetically Modified; D001646:Bile / Q000378:metabolism; D001790:Blood Physiological Phenomena; D001794:Blood Pressure; D006439:Hemodynamics; D006499:Hepatic Artery / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000098:blood supply / Q000502:physiology*; D008102:Liver Circulation; D010477:Perfusion; D012256:Riboflavin / Q000031:analogs & derivatives* / Q000235:genetics*; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000502:physiology*; D014184:Transplantation, Homologous / Q000502:physiology
C007701:factor 420; D012256:Riboflavin