208 Purpose of the study: The major problem in xenotransplantation (XT) is, that the hyperacute xenograft rejection (HXR) after XT causes xenograft failure within minutes or a few hours due to natural antibodies (XNAb) and activation of the complement system. As a preclinical model to prevent HXR after orthotopic xenotransplantation (oXHTx) of pig hearts to baboons we used immunoapheresis (IA) of immunoglobulins (Ig) with the reusable Ig-Therasorb® column. Methods: We performed three oXHTx of landrace pig hearts to baboons (19±6,8 kg) using extracorporeal circulation (EC) connected to 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 coated with polyclonal sheep-antibodies against human IgG, IgM and IgA. Intraoperative treatment consisted of 4 cycles of IA. For control we performed oXHTx of one baboon (16,9 kg) without IA. Perioperatively serum concentrations of Ig, anti-pig antibodies, complement and cardiac enzymes were determined. Tissue samples of myocardium were taken at the end of the study for immunohistochemical examinations, light microscopy (LM) and electron microscopy (EM). For cardiac monitoring after oXHTx we used electro-, echocardiography and invasive measurement of cardiac output. A mismatch of donor and recipient heart size was prevented by selecting a 30%-40% lower weight of donor pigs than recipients. Results: 4 cycles of IA removed more than 75% of IgG, IgM and IgA from plasma. The graft of the control animal failed after 29 min. First oXHTx with IA was selectively terminated after 100 min, the second oXHTx after 11 hours and the third oXHTx after 21 hours without any histological signs of HXR. After weaning off EC these donor xenografts showed sufficient function with sinus rhythm without ST-segment elevation, excellent cardiac out-put in echocardiography and invasive measurement (1,93±0,035 l/min). Serological parameters indicating cardiac damage were significantly lower after IA compared to the control experiment. Macroscopically the xenograft of the control animal showed massive hemorrhage in comparison with the nearly inconspicuous graft after IA. The myocardium of IA group demonstrated less deposits of Ig and complement components compared to the control animal. Conclusion: Baboons survive HXR of xenotransplantation after antibody depletion by Ig-Therasorb column. In our experiment only 4 cycles of immunoapheresis effectively prevent HXR in oXHTx of baboons. IA is a re-usable method and can be handled easily in combination with the EC. Long-term survival in orthotopic baboon xenotransplantation model especially in combination with IA and transgenic pig organs could be a reliable preclinical trial for XT in clinical patients. Further trials are necessary to evaluate also a possible employment of IA in delayed and chronic humorally mediated xenograft rejection.