Ig-Therasorb immunoapheresis in orthotopic xenotransplantation of baboons with landrace pig hearts

Background. The major problem of xenotransplantation is, that hyperacute xe nograft rejection (HXR) causes graft failure within minutes or a few hours because of natural antibodies and activation of the complement system. As a preclinical model we transplanted pig hearts orthotopically into baboons. To prevent HXR after orthotopic xenotransplantation (oXHTx), the immunoglob ulins (Ig) and natural antibodies were adsorbed to reusable Ig-Therasorb(R) immunoadsorption (LA) columns, Methods, We performed three oXHTx of landrace pig hearts into baboons (19+/ -6.8 kg), using extracorporeal circulation (ECC) connected to the IA unit, After separating the recipient's blood into plasma and cellular fraction by a plasma filter, plasma flow was directed to the Ig-Therasorb column coate d with polyclonal sheep-antibodies against human IgG, IgM, and IgA, Intraop erative treatment consisted of 4 cycles of LA. For a control, we transplant ed one pig heart into a baboon (16.9 kg) without applying IA. Perioperative ly, serum concentrations of Ig, anti-pig-antibodies, complement and cardiac enzymes were determined, Tissue samples of myocardium were collected at th e end of the study for immunohistochemical examinations, light microscopic examination (LM) and electron microscopic examination (EM), For cardiac mon itoring after oXHTx, we used EGG, echocardiography, and invasive measuremen t of cardiac output, To prevent a mismatch of donor and recipient heart siz e, the donor pig had a 30-40% lower body weight than the recipient baboon. Results. Four cycles of IA removed >80% of IgG, IgM, and IgA from plasma. T he graft of the control animal failed after 29 min. The first oXHTx with ZA was intentionally terminated after 100 min, the second oXHTx after II hr a nd the third oXHTx after 21 hr, All xenografts showed no histological signs of HXR, After weaning off ECC, these donor hearts worked in sinus rhythm w ithout electrocardiographic ST-segment elevation, An excellent cardiac outp ut was measured by echocardiography and thermodilution (2 L/min), Serologic al parameters indicating cardiac damage were significantly lower after IA i f compared with the control experiment, Macroscopically, the xenograft of t he control animal showed massive hemorrhage in comparison with the almost i nconspicuous grafts after LA, The myocardium of the LA group demonstrated f ewer deposits of Ig and complement components compared with the control ani mal, Conclusion. Baboons do not hyperacutely reject a porcine xenograft after an tibody depletion by the Ig-Therasorb column. In our experiment only 4 cycle s of immunoapheresis effectively prevented HXR after oXHTx of baboons, The Ig-Therasorb column is a reusable device, which can be handled easily in co mbination with the ECC, IA must be tested in oXHTx longterm survival experi ments, especially in combination with transgenic pig organs, which could be a reliable preclinical approach for future clinical xenotransplantation.