Improving Clinical and Experimental Normothermic Ex situ Liver Perfusion 
For Future Application

• Author / Creator

  Bral, Mariusz

• The past decade seen an increasing interest in ex situ normothermic liver machine perfusion as a promising alternative preservation strategy for potential expansion of the donor pool. Herein, my intent is to place my own contributions to this field within the greater context of ex situ liver perfusion, and trust that the reader may appreciate how these may further potentially advance our appreciation of how NMP technology may be more optimally applied to graft preservation and assessment. The two experimental ex situ NMP studies that we published previously addressed basic but important questions concerning NMP circuit priming, and the validity of ‘on circuit’ transaminase measurement for viability assessment. Before these studies, the kinetics of transaminase production, degradation and clearance within a closed ex situ circuit were not known. Our first published clinical NMP series was the first time that this technology was applied in North America. That study demonstrated that NMP technology was safe and feasible in a Canadian setting, and addressed the unique potential of ex situ perfusion to disrupt established transplant practice within the context of a geographically vast land. The second published clinical series (Bral shared first authorship), is the first published study to demonstrate both ongoing utility and increased practicality with a ‘back-to-base’ implementation strategy that avoids a need to transport heavy and complex machinery between the donor and recipient centres. Looking towards the next iterative steps in application of NMP technologies, we applied an in vivo murine ischemia reperfusion model as a screening tool to assess the efficacy of selected therapeutics, with the intention of prescreening these compounds for future translational application into an experimental ex situ
  II
  liver circuit. Most of these publications have been cited in the discourse surrounding NMP, and we trust have formed part of the foundation on which the technology will move into the future.

• Subjects / Keywords

  • liver ex situ perfusion

• Graduation date

  Fall 2019

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-75yw-ez62

• License

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