J Korean Surg Soc.  2008 Nov;75(5):287-295.

A Pig to Canine Auxiliary Hepatic Xenotransplantation Model: Prevention of Hyperacute Rejection via Blocking the Kupffer Cells and Regulating the Complement Family

• Park JJ
• Chung KY
• Lee JE
• Yom CK
• Lee JG
• Ahn HJ
• Oh SK
• Sung SH
• Kang BC
• Han KH

Abstract

PURPOSE
We designed a pig to canine liver xenotransplantation model to study the diverse immunologic and hemodynamic consequences that follow xenotransplantation and hyperacute rejection.
METHODS
The animals were divided into two groups: the cobra venom factor and Gadolinium chloride treatment group (CVF+Gd group) (3 cases) and the control group (3 cases). The donor pig's whole liver was harvested, and then the harvested pig's whole liver was transplanted into a dog after the dog underwent left hepatectomy. After reperfusion of the graft, blood samples were taken 20, 40 and 60 minutes after reperfusion, and the liver, lung and kidney tissues were taken 1 hour after reperfusion.
RESULTS
In the control group, the grafts showed a patchy hypoperfused liver surface and it felt rubbery solid compared to the CVF+Gd group. The serum total protein, albumin, fibrinogen and platelets decreased abruptly and there were no significant differences between the two groups. The serum PT, PTT and FDP were increased in both groups and the CVF+Gd group showed a more obtuse slope than the control group. We could not find any intravascular pathologic changes on the microscopic findings of the graft. Only scant intravascular fibrin deposition was found. Hepatocellular vacuolization and sinusoidal dilatation were also found. There were patches of necrosis without any zonal distribution, intrasinusoidal neutrophil sequestration and interstitial hemorrhage. These findings were milder in the CVF+Gd group.
CONCLUSION
The pig to canine partial auxiliary liver xenotransplantation model is feasible and it is a good model before starting to perform pig to primate liver xenotransplantation. In the CVF+Gd group, pathologic findings like patch hepatocyte necrosis etc. were less severe. As there were no corresponding vascular pathologic findings, these findings are not the direct effect of CVF and gadolinium treatment, and so other factors like Ischemia- reperfusion injury should be considered.

Keyword

Xeno-liver transplantation; Pig to canine; Cobra venom factor

MeSH Terms

Animals
Blood Platelets
Cobra Venoms
Complement System Proteins
Dilatation
Dogs
Fibrin
Fibrinogen
Fluconazole
Formycins
Gadolinium
Hemodynamics
Hemorrhage
Hepatectomy
Hepatocytes
Humans
Kidney
Kupffer Cells
Liver
Lung
Necrosis
Neutrophils
Primates
Rejection (Psychology)
Reperfusion
Reperfusion Injury
Ribonucleotides
Tissue Donors
Transplantation, Heterologous
Transplants
Cobra Venoms
Complement System Proteins
Fibrin
Fibrinogen
Fluconazole
Formycins
Gadolinium
Ribonucleotides