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Pig lung transplant survival model

Nature Protocols volume 13, pages 1814–1828 (2018)Cite this article

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Abstract

Although lung transplant is a life-saving therapy for some patients, primary graft dysfunction (PGD) is a leading cause of mortality and morbidity soon after a transplant. Ischemia reperfusion injury is known to be one of the most critical factors in PGD development. PGD is by definition an acute lung injury syndrome that occurs during the first 3 d following lung transplantation. To successfully translate laboratory discoveries to clinical practice, a reliable and practical large animal model is critical. This protocol describes a surgical technique for swine lung transplantation and postoperative management for a further 3 d post transplant. The protocol includes the background and rationale, required supplies, and a detailed description of the donor operation, transplant surgery, postoperative care, and sacrifice surgery. A pig lung transplant model is reliably produced in which the recipients survive for 3 d post transplant. This 3-d survival model can be used by lung transplant researchers to assess the development of PGD and to test therapeutic strategies targeting PGD. In total, the protocol requires 5 h for the surgeries, plus ~2 h in total for the postoperative care.

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Fig. 1: Donor surgery.
Fig. 2: Recipient surgery.
Fig. 3: Post operative care.

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Acknowledgements

This work was supported by research grants from the Canadian Institutes of Health Research (MOP-312227, MOP-119514, and PJT-148847) and an Ontario Research Fund-Research Excellence award (RE08-29).

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Authors and Affiliations

  1. Department of Thoracic Surgery, Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Toronto, ON, Canada

    Andrea Mariscal, Lindsay Caldarone, Jussi Tikkanen, Daisuke Nakajima, Manyin Chen, Jonathan Yeung, Marcelo Cypel, Mingyao Liu & Shaf Keshavjee

  2. Toronto Lung Transplant Program, Department of Thoracic Surgery, University Health Network, Toronto, ON, Canada

    Andrea Mariscal, Jussi Tikkanen, Daisuke Nakajima, Jonathan Yeung, Marcelo Cypel & Shaf Keshavjee

  3. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    Andrea Mariscal, Lindsay Caldarone, Marcelo Cypel, Mingyao Liu & Shaf Keshavjee

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  1. Andrea Mariscal
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Contributions

All authors contributed critical feedback to the development of the protocol. A.M. took the lead in performing the surgeries and writing the manuscript with the help of L.C. L.C., D.N., and M. Chen assisted with surgeries. J.T., J.Y., M. Cypel M.L., and S.K. were involved in planning and supervising the research.

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Correspondence to Mingyao Liu or Shaf Keshavjee.

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Key reference using this protocol

Machuca, T.N., et al. Hum. Gene Ther. 28, 757–765 (2017) https://doi.org/10.1089/hum.2016.070

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Mariscal, A., Caldarone, L., Tikkanen, J. et al. Pig lung transplant survival model. Nat Protoc 13, 1814–1828 (2018). https://doi.org/10.1038/s41596-018-0019-4

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