Korean J Thorac Cardiovasc Surg.  2004 May;37(5):391-400.

Effect of Antibody Titer on Xenograft Survival in Pig-To-Dog Heterotopic Cardiac Xenotransplantation: Opening of Xenotransplantation Era

• Lee JR
• Kim HK
• Kim JY
• Choi DY
• Lee JH
• Wi HC
• Kang HJ
• Kim YT
• Kang BC
• Kim JS
• Lee HM
• Kwak JG
• Lee DS
• Ahn CR

Abstract

BACKGROUND: Xenotransplantation in discordant species results in immediate and irreversible hyperacute rejection due to natural antibodies, IgM. With this, antibody depletion is one option to reduce hyperacute rejection, we investigated the effect of PCPP (postcentrifugal plasmapheresis) on the depletion of natural antibodies and the effect of antibody titer on xenograft survival. MATERIAL ANDMETHOD: Outbred swines (n=4) weighing 10~20 kg were used as donors and mongrel dogs (n=4) weighing 25~30 kg were used as recipients. Recipient canines underwent plasmapheresis (COBE TPE Laboratories, Lakewood. CO, USA). Pre-transplantation PCPP was performed on day - 2 and day 0. There were three groups (Group 0: no PCPP, Group 1: 1 pla sma-volume (PV) at day 2 and 2 PV at day 0, Group 2: 2 PV at day - 2 and 2 PV at day 0). A swine heart was heterotopically transplanted into a recipient's abdominal infrarenal aorta and inferior vena cava. Mean percent depletion of total IgM and IgG in plasma of the recipients was calculated. Serum albumin, elecctrolyte, complement activity and coagualtion factors were measured. Histopathologic examination of heart specimens was performed. RESULT: Mean percent depletion of IgM and IgG were 95.7+/-1.2%, 80.5+/-2.4% in the group 2 at the end of PCPP. The percent depletion of serum albumin concentration was decreased from 2.8 to 1.4 g/dL in the group 1 and 3.0 to 1.5 g/dL in the group 2. Complement hemolytic activity was decreased in group 1 and 2, but returned to normal level within 24 hours. Complement hemolytic activity was reduced to 10% of pre-PCPP level in group 2. Serum fibrinogen decreased to 20% or less and was recovered within 24 hours in group 2. Antithrombin III decreased but less than fibrinogen. PT and aPTT were sometimes but not always prolonged during plasmapheresis. After plasmapheresis, PT and aPTT were prolonged beyond the measurable level. D-dimer was not found during PCPP, but appeared and maintained from 10 minutes after transplantation. Graft survival time was 5 min in group 0, and it was 90+/-0 min in the group 2. Histopathologic changes were more typically characterized by edema, hemorrhages, thrombosis in all groups at the end of experiment.
CONCLUSION
PCPP effectively removed immuoglobulins and reduced the titer of natural antibodies, as a result, significantly prololonged swine heart xenograft survival.

Keyword

Xenotransplantation; Plasmapheresis; Graft rejection; Antibodies; Animal models

MeSH Terms

Animals
Antibodies
Antithrombin III
Aorta
Complement System Proteins
Dogs
Edema
Fibrinogen
Graft Rejection
Graft Survival
Heart
Hemorrhage
Heterografts*
Humans
Immunoglobulin G
Immunoglobulin M
Models, Animal
Plasma
Plasmapheresis
Serum Albumin
Swine
Thrombosis
Tissue Donors
Transplantation, Heterologous*
Vena Cava, Inferior
Antibodies
Antithrombin III
Complement System Proteins
Fibrinogen
Immunoglobulin G
Immunoglobulin M
Serum Albumin