Cao, Yiming (2017) Expanding the Organ Pool: An Exploration of Experimental and Clinical Interventions to Benefit Transplantation using Livers Following Donation after Circulatory Death. Masters thesis, Victor Chang Cardiac Research Institute.
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2017 Yiming Cao _Masters Thesis _Liver Tx DCD _VCCRI UNSW.pdf Download (3MB) | Preview |
Abstract
Liver transplantation is a highly efficacious intervention for end stage liver failure. Unfortunately, there is considerable waiting time for suitable donor organs leading to significant post-operative morbidity and mortality from marginal donors and recipients, as well as through attrition on the waiting list. The introduction of donation after circulatory death (DCD) organs has to some extent relieved the stress on the waiting list, but unfortunately, these organs are associated with worse outcomes than the more traditional form of donation – donation after brain death. As such, interventions to improve these organ qualities are pivotal in facilitating maximal benefit to be derived from these valuable donations. The current thesis seeks to explore such measures from an experimental and clinical perspective. The former is with regards to the design of a clinically applicable large animal model of donation after circulatory death, followed by ex situ perfusion of the isolated liver. The latter is concerned with donor practices, especially life support withdrawal practices and administration of ante-mortem heparin, that can be modified to benefit the recipient without impacting on the end of the life care of the donor. Our experimental results demonstrated the feasibility of maintaining the hepatocellular function for up to 4 hours using ex situ perfusion of livers retrieved under a clinical DCD protocol. Potential mechanisms are discussed, but it is clear that ex situ perfusion is able to mitigate a portion of the damage incurred by the liver during the preceding warm ischaemia. Furthermore, our clinical results indicate that further minimisation of the warm ischaemic time by withdrawing donor life support in the operating theatre as opposed to intensive care unit can confer significant benefit upon the recipient, with additional benefits afforded by administration of ante-mortem heparin. In conclusion, we have been able to demonstrate that warm ischaemia is a critical factor in determining subsequent recipient outcomes, and minimisation of this time period even within the acceptable threshold of 30 min can have significant benefits. Once warm ischaemia has occurred, it is possible to reverse some of the damage. This can be achieved by normothermic ex situ perfusion, a technique that should be subject to more rigorous investigation in a clinical or clinically applicable animal setting in the future.
| Item Type: | Thesis (Masters) |
|---|---|
| Additional Information: | Supervisor: Dhital, Kumud, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW; Macdonald, Peter, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW; Pleass, Henry, Westmead Hospital, Sydney Medical School, USYD |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 08 Aug 2017 22:25 |
| Last Modified: | 08 Aug 2017 22:25 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/617 |
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