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Modification of Hyperacute Xenograft Rejection of a Porcine Kidney by Serial Organ Perfusion of Canine Blood Through the Pig's Liver and Kidney

Other Title
이종 간장 및 신장을 통한 자연항체 흡수 후 이종이식 신장에서의 초급성 거부반응 변화에 관한 연구
Authors
오, 창권; 정, 현주; 김, 주형; 왕, 희정; 김, 명욱
Citation
Taehan Oekwa Hakhoe, 56(1):1-19, 1999
Journal Title
Taehan Oekwa Hakhoe; 대한외과학회지
ISSN
1226-0053
Abstract
Background : The major problem in transplants between widely disparate species is

hyperacute rejection, a rapid and violent rejection that damages the graft within minutes

or hours. Hyperacute rejection is mediated by the components of natural immunity, most

notably natural antibodies and complements. The absorption of natural antibodies on

endothelial cells by passing the recipient's blood through a donor kidney or liver is very

effective in removing xenoreactive natural antibodies from a recipient's blood. To modify

hyperacute rejection in a pig-to-dog renal transplant, we transplanted a porcine kidney,

which had been perfused after organ perfusion of canine blood through a pig's liver and

kidney, was transplanted on-bloc with the kidney.

Methods : The en-bloc organ procurement from male pigs weighing 15∼20 ㎏,

including the liver and two kidneys, was performed after perfusion with a cold

Euro-Collins solution through the aorta and portal vein. The harvested organs were

vascularized to male dogs weighing 25∼30 ㎏ by anastomosis of the graft aorta to the

recipient's infrarenal aorta, the graft inferior vena cava to the recipient's infrarenal

inferior versa cava, and the graft portal vein to the recipient's portal vein with a

end-to-side fashion. The recipient's blood was perfused into the liver and one kidney

and then into the other kidney 60 minutes later. During the procedure, the recipient's

blood was sampled and assayed for natural xenoreactive antibodies. Natural anti-porcine

endothelial antibodies were measured by ELISA with porcine aortic endothelial cells in

the culture as targets. Each grafted organ was biopsied serially at 2, 4, 6, 8, 10, 20, 40,

and 60 minutes after reperfusion for light microscopic and immunofluorescent

examinations.

Results : Natural anti-porcine endothelial antibody levels(both IgM and IgC) of canine

serum decreased at 60 minutes after organ perfusion of canine blood through a porcine

lifter and one kidney. Hyperacute rejection (capillary congestion, interstitial hemorrhage,

thrombosis, etc.) of the kidneys appeared within 20 minutes after blood perfusion

regardless of organ absorption of natural antibodies through the porcine liver and one

kidney. The appearance of interstitial hemorrhage and thrombosis of the kidney was

delayed about 4∼10 minutes by organ absorption of natural antibodies. However, acute

tubular necrosis appeared early and more obviously in the second kidneys.

Immunofluorescence showed granular deposits of canine IgM and IgG in the glomerular

mesangium and on the microvessels. Canine IgM, but not IgG, deposition on the second

kidney decreased after organ absorption of natural antibodies. Complement deposition

was not altered by organ absoption.

Conclusions : The organ perfusion of canine blood through a porcine liver and kidney

was effective for only a short time in decreasing the natural anti-porcine endothelial

IgM and IgG antibodies of canine serum, and histologic changes appeared in the second

kidney of a slightly later time than in the kidney used in antibody absorption. Further

efforts should be made toward modifying the technique for removal of specific natural

antibodies and complements.
Keywords
XenotransplantationHyperacute xenograft rejectionNatural xenoreactive antibodies
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Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
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