Iyer, Arjun (2017) Cardiac allografts from donation after circulatory death donors – are these hearts viable for use in cardiac transplantation? PhD thesis, Victor Chang Cardiac Research Institute.
Preview |
Text
2017 Arjun Iyer _PhD Thesis Cardiac allografts VCCRI UNSW.pdf Download (6MB) | Preview |
Abstract
Cardiac Transplantation remains the definitive treatment of End-Stage Heart Failure beyond medical therapy, with excellent recipient survival and quality of life. However, its major limitation remains in the finite number of cardiac allografts available for transplantation. Whilst all hearts have previously been procured solely from brain dead donors, the search for additional sources of organs have led investigators to Donation after Circulatory Death (DCD) donors. The body of work enclosed in this thesis investigates the viability of hearts from these DCD donors for use in cardiac transplantation. These hearts have been avoided, having been exposed to varying periods of warm ischaemia - referring to hypoxic and hypoperfusion insults at normothermic conditions. However, there is inherent tolerance to these insults prior to irreversible damage. The initial series of experiments utilised a large animal model to investigate the warm ischaemic time (WIT) limit prior to irrecoverable damage at a biochemical, metabolic & functional level. These studies demonstrated irrecoverable damage beyond 20 minutes WIT. However, utilising post-conditioning strategies aimed at activating cellular protective pathways, tolerance could be increased to 30 minutes. The next series of experiments were aimed at demonstrating clinical relevance. Utilising a large animal orthotopic transplant model, post-conditioned hearts exposed to 30 minutes WIT were transplanted into recipient animals following 4 hours of storage. Storage of the allografts were either through the current standard of care (cold storage) or with ex-vivo perfusion (EVP) preservation (Transmedics OCS). Superiority and viability of cardiac allografts post-transplantation were only demonstrated when preserved with EVP. Based on these results and a series of human pre-clinical studies, the first human DCD cardiac transplant of the modern era was performed in July 2014. The series of the first 3 of these heart transplants was published in the LANCET journal as a major medical breakthrough. Since 2014, a total of 14 clinical DCD heart transplants have been performed with all recipients discharged home. These results demonstrate successful clinical translation of the animal studies. It also aptly responds to the question posed in the title of this thesis – that these hearts are truly viable for use in cardiac transplantation.
| Item Type: | Thesis (PhD ) |
|---|---|
| Additional Information: | SUPERVISORS: Macdonald, Peter, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW; Dhital, Kumud, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 08 Aug 2017 22:18 |
| Last Modified: | 08 Aug 2017 22:19 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/616 |
Actions (login required)
 |
View Item |