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Eur J Cardiothorac Surg 2005;28:149-156
© 2005 Elsevier Science NL

Pre-treatment of donor with 1-deamino-8-D-arginine vasopressin could alleviate early failure of porcine xenograft in a cobra venom factor treated canine recipient

^a Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, South Korea
^b Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, South Korea
^c The Xenotransplantation Research Center, Seoul National University Hospital, Seoul, South Korea

Received 8 September 2004; received in revised form 15 February 2005; accepted 21 February 2005.

^* Corresponding author. Address: Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, South Korea. Tel.: +82 2 2072 3161; fax: +82 2 765 7117. (Email: ytkim{at}snu.ac.kr).

Objective: Unlike cardiac or renal xenotransplants, the depletion of complement using cobra venom factor (CVF) does not improve pulmonary xenograft survival. Several cases suggest that the swine von Willebrand factor (vWF) may play a major role in presenting a different pathogenesis of pulmonary xenograft dysfunction from other organs. To evaluate the role of vWF and the complement system in mediating hyperacute vascular injury of pulmonary xenografts and elucidate pathogenesis of the injury, we performed swine-to-canine orthotropic single lung xenotransplantation after pre-treatment of 1-deamino-8-D-arginine vasopressin (DDAVP) and CVF. Methods: We set up three groups for lung xenotransplantation: group I served as the control group; group II, recipients pre-treated with CVF; group III, donors pre-treated with DDAVP (9mg/kg, 3 days)/recipients pre-treated with CVF (60u/kg). Hemodynamic data, coagulation and complement system parameters, and grafted lung pathologies were examined serially for 3h after transplantation. Results: DDAVP infusion reduced the vWF content in swine lung tissue in vivo (7.7±2.4AU/mg vs 16.0±5.6AU/mg, P<0.0001). Infusion of CVF 24h prior to transplantation effectively depleted the recipient's serum C3 and complement hemolytic activity below the detectable range. Regardless of the use of CVF, both groups I and II transplanted with unmodified grafts showed an immediate drop in leukocytes and platelet counts after transplantation. However, in group III, in recipients transplanted with DDAVP pre-treated swine lung, the platelet count did not decrease after transplantation (P=0.0295). The decrease of plasma antithrombin and fibrinogen tended to be attenuated in group III. Light microscopic examination revealed extensive vascular thromboses in both capillary and larger vessels, as well as early pulmonary parenchymal damage in groups I and II, but were rarely observed in group III. Conclusions: Complement inhibition alone was not enough to alleviate intravascular thrombosis, the main pathology in pulmonary xenotransplantation. Pre-infusion of DDAVP to the donor animal was effective in preventing platelet sequestration and attenuated intravascular thrombosis. It is suggested that the strategies targeting vWF would be promising for successful pulmonary xenotransplantation.

Key Words: Hyperacute rejection • Pulmonary xenotransplantation • Platelet • Desmopressin • Thrombosis