Document Detail

Combination of hDAF-transgenic pig hearts and immunoadsorption in heterotopic xenotransplantation of immunosuppressed baboons.
MedLine Citation:
PMID:  15808683     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Hyperacute xenograft rejection (HXR) and acute vascular rejection (AVR) after xenotransplantation are triggered by xenoreactive antibodies (XAb) and an activated complement cascade. In a heterotopic (abdominal) xenotransplantation model we combined immunoadsorption (IA, Ig-Therasorb column) and a quadruple immunosuppressive drug therapy in recipient baboons with donor pig hearts transgenic for human decay accelerating factor (hDAF). METHODS: According to XAb titers between 6 and 14 cycles of IA were performed preoperatively in 4 recipient baboons (18.6 +/- 2.5 kg). Hearts of hDAF-transgenic donor pigs (6.1 +/- 1.1 kg, Imutran Ltd., a Novartis Pharma AG Company, Basel, Switzerland) were heterotopically transplanted using the abdominal technique in baboons. Immunosuppression consisted of cyclophosphamide (CyP) induction therapy, ERL080 (Novartis Pharma AG), cyclosporin A (CyA, Neoral), and steroids. Blood levels of mycophenolate, CyA, immunoglobulins (Ig), anti-pig-antibodies, complement factors, and cardiac enzymes were determined. Abdominal electrocardiography (ECG), echocardiography, and palpation were used for monitoring of the pig hearts. Myocardial tissue specimens were examined using immunohistochemistry, light microscope (LM), and electron microscope (EM). RESULTS: Ten cycles of IA alone removed 78% of XAb and accordingly IgM, IgG, IgA, complement C3, and C4. None of the xenografts was hyperacutely rejected, but xenograft failure occurred after 5.0 +/- 1.3 days (range, 2.4-8.0 days) because of an AVR associated with a rapid XAb increase within 24 hours. White blood cell count (10.3 +/- 2.2 G/L) showed a maximum of 13.1 +/- 2.1 (day 1) and constant levels (1.4 +/- 0.3-2.1 +/- 1.3 G/L) between day 3 and 6. Histology (LM/EM) showed massive hemorrhage, necrosis, and vascular thrombi as signs of AVR. CONCLUSION: Although HXR was prevented by using IA and hDAF-transgenic donor hearts, AVR was not avoided due to insufficient immunosuppressive regimen used and a missed postoperative IA treatment as a result of an inefficient control of XAb production.
P Brenner; M Schmoeckel; C Wimmer; A Rucker; V Eder; S Uchita; U Brandl; M Hinz; T Felbinger; B Meiser; C Hammer; H Reichenspurner; B Reichart
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation proceedings     Volume:  37     ISSN:  0041-1345     ISO Abbreviation:  Transplant. Proc.     Publication Date:    2005 Jan-Feb
Date Detail:
Created Date:  2005-04-05     Completed Date:  2005-10-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0243532     Medline TA:  Transplant Proc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  483-6     Citation Subset:  IM    
Klinikum-Grosshaein, University of Munich, Munich, Germany.
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MeSH Terms
Adrenal Cortex Hormones / therapeutic use
Animals, Genetically Modified
Antibodies, Heterophile / blood
Antigens, CD55 / genetics*
Heart Transplantation / immunology*
Immunosorbent Techniques
Immunosuppressive Agents / therapeutic use
Mycophenolic Acid / therapeutic use
Transplantation, Heterologous
Reg. No./Substance:
0/Adrenal Cortex Hormones; 0/Antibodies, Heterophile; 0/Antigens, CD55; 0/Immunosuppressive Agents; 24280-93-1/Mycophenolic Acid

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