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J Thorac Cardiovasc Surg 1999;118:805-814
© 1999 Mosby, Inc.

CARDIOTHORACIC TRANSPLANTATION

CHARACTERIZATION OF A PIG-TO-GOAT ORTHOTOPIC LUNG XENOTRANSPLANTATIONMODEL TO STUDY BEYOND HYPERACUTE REJECTION

From the ^aDepartment of Thoracic and Vascular Surgery, andHeart-Lung Transplantation and Experimental Surgical Laboratory, HôpitalMarie-Lannelongue, Le Plessis Robinson, Paris-Sud University.^bINSERMU 504 Villejuif; and the ^cLaboratory of Experimental Surgery, FondationTransplantation, Strasbourg, France.

Address for reprints: Paolo Macchiarini, MD, PhD, Department of Thoracicand Vascular Surgery, Heidehaus Hospital (Hannover Medical School), Am Leineufer,70, 30419 Hannover, Germany (E-mail: pmacchiarini{at}compuserve.com).

Background: A pig-to-goat orthotopiclung xenograft model was developed to test whether depletion of goat xenoreactiveantibodies against pig red blood cells would prolong pig lung xenograft survival.
Methods: Adult goats with anti-pig xenoreactive antibodiesunderwent left pneumonectomy followed by orthotopic transplantation of pigleft lung (group 1) or immunodepletion of their xenoreactive antibodies byextracorporeal right pig lung perfusion before transplantation without (group2) or with (group 3) complete clampage of the right pulmonary artery. In group4, goat left lungs were orthotopically transplanted into pigs and served asnegative controls (pig serum does not have anti-goat xenoreactive antibodies).Each study group included 5 animals. Immunosuppression in surviving recipientsincluded cyclosporine and azathioprine.
Results: Group 1 recipients died 7 ± 3 hours after xenograft reimplantationof severe pulmonary hypertension and dysfunction and vasogenic shock, withlittle evidence of histologic xenograft injury. Group 2 xenografts had a stablecirculatory and respiratory function on reperfusion and survived 9 ±4 days. Group 3 animals also tolerated complete occlusion of the right pulmonaryartery, and xenografts assured the total respiratory support for 4 ±1 days. After immunodepletion, goat serum showed no detectable titers of xenoreactiveantibodies, which began to reappear by postoperative day 2, where xenograftsshowed histologic stigmata of acute (humoral and cellular-mediated) rejectionthat evolved to a complete xenograft necrose at death. Group 4 xenograftsshowed scattered features of acute rejection 5 ± 1 days after the operation.
Conclusions: Pig left lung xenografts can provide prolongedand complete respiratory support after depletion of goat xenoreactive antibodies,but they ultimately necrose once recipient xenoreactive antibodies returnto pretransplantation values.

Supported by the Xenotransplantation project within the European Communityprogram DGXII Biotechnology (shared cost BI04-CT97-2242 and concerted action3026PL950004) and Fondation Transplantation.