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Right arrow Lung - transplantation

J Thorac Cardiovasc Surg 2009;137:486-491
© 2009 The American Association for Thoracic Surgery

Transplantation

A mouse model of orthotopic, single-lung transplantation

Wolfgang M. Jungraithmayr, MD*, Stephan Korom, MD, Sven Hillinger, MD, Walter Weder, MD

Division of Thoracic Surgery, University Hospital Zürich, Zürich, Switzerland

Received for publication August 1, 2008; revisions received September 15, 2008; accepted for publication October 4, 2008.

* Address for reprints: Wolfgang M. Jungraithmayr, MD, Division of Thoracic Surgery, University Hospital Zürich, Rämistrasse 100, CH - 8091 Zürich, Switzerland. (Email: wolfgang.jungraithmayr{at}usz.ch).

Objectives: Progress in studying acute and chronic pulmonary allograft rejection has been hampered by the lack of feasible experimental animal transplantation models. Contemporary approaches are limited by anatomic applicability (heterotopic tracheal implantation) and lack of genetic variability (rat model). To utilize the breadth of available genetic modifications in a physiologic setup, we optimized and validated a procedure of orthotopically transplanted, perfused, and ventilated single pulmonary transplantation in mice.

Methods: C57BL/6 mice served as recipient, with Balb/c as donor. At time of harvest, explanted lungs were perfused with Perfadex, and the heart–lung block excised. Under 30 to 40x magnification, vessels and bronchus were cuffed. Following left thoracotomy in the recipient, hilar structures were incised and cuff-anastomosed with the corresponding donor parts. Allogeneic and syngeneic transplantations (n = 12/group) were performed with a follow-up period of 5 days and up to 90 days, respectively.

Results: The success rate of lung transplantation in mice was 87.5% (21/24). Mean cold ischemia time was 32.3 ± 3.7 minutes, and warm ischemia time was 30.8 ± 9.5 minutes. Deaths were due to bleeding during dissection of the hilus and/or caused by thrombosis postoperatively. Allogeneic grafts were rejected by day 5; syngeneic grafts were slightly congested but mainly unchanged up to day 90 posttransplantation.

Conclusions: Unilateral lung transplantation in mice can be performed in a standardized and controlled fashion with low mortality, comparable to the rat. Employing transgenic and knockout mice strains, this procedure holds great promise to advance the understanding of immunologic pathways in acute and chronic rejection in a physiologic model of pulmonary transplantation.

Abbreviations and Acronyms LA = left atrium; LB = left bronchus; PA = pulmonary artery; PV = pulmonary vein






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