Thorac Cardiovasc Surg 2006; 54 - PP_81
DOI: 10.1055/s-2006-925863

Combination of hDAF-transgenic pig hearts and immunoadsorption in heterotopic xenotransplantation of immunosuppressed baboons

P Brenner 1, M Schmoeckel 1, H Reichenspurner 2, C Wimmer 1, A Rucker 1, V Eder 1, S Uchita 1, U Brandl 1, T Felbinger 3, BM Meiser 1, C Hammer 4, B Reichart 1
  • 1Dept. of Cardiac Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany
  • 2Dept. of Cardiovascular Surgery, University of Hamburg, Hamburg, Germany
  • 3Dept. of Anesthesiology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany
  • 4Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany

Objectives: Hyperacute xenograft rejection (HXR) and acute vascular rejection (AVR) after xenotransplantation is 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 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 four recipient baboons (18.6±2.5kg). Hearts of hDAF-transgenic donor pigs (6.1±1.1kg, from Novartis Comp.) were heterotopically transplanted in abdominal technique in baboons. Immunosuppression consisted of cyclophosphamide induction therapy, ERL (Novartis Comp.), cyclosporin A (CyA, Neoral) and steroids. Blood levels of mycophenolate, CyA, immunoglobulins, anti-pig-antibodies, complement factors and cardiac enzymes were determined. Myocardial tissue specimens were examined by immunohistochemistry, light (LM) and electron microscope (EM).

Results: Ten cycles of IA alone removed 78% of XAb and accordingly IgM/-G/-A, complement C3 and C4. None of the xenografts was hyperacutely rejected, but xenograft failure occurred after 5.0±1.3 days (2.4–8.0 days) because of an AVR associated with a rapid XAb increase within 24h. White blood cell count (10.3±2.2 G/l) showed 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 employed and a missed postoperative IA treatment as a result of an inefficient XAb control.