29 Apr Comparing Liver Transplants after Circulatory vs Brain Death
MedicalResearch.com Interview with:
Mr. Thamara Perera FRCS
Consultant Surgeon – Multi Organ Retrieval and Liver Transplant
Liver Transplant – University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre,
Birmingham, UK
MedicalResearch.com: What are the main findings of the study?
Answer: In this study we compared the basic energy metabolism of liver grafts obtained from conventional and widely practiced form of organ donation, the donation after brain death (DBD) donors, and recently revived form of organ donation called donation after circulatory death (DCD) donors. To introduce a background to this study – DCD liver grafts are perceived as marginal liver grafts, owing to the basic differences surrounding the organ donation. DCD organs suffer a period of warm ischemia from the time of treatment withdrawal in a potential donor up until the organs are actually recovered and preservation is initiated. Although the DCD liver grafts have supplemented the donor organ pool, the initial and short-term results following liver transplantation are comparatively poor and these differences are attributable to the donor warm ischemia. However there were no studies in the literature examining the energy status of DCD liver grafts and our study is the first such study.
In our study we used a technique called “Microdialysis” to sample the tissue fluid from the liver grafts procured from DBD and DCD donors. Microdialysis is a technique where small micro-millilitre amounts of tissue fluid is sampled via a semi-permeable membrane mounted at the end of a disposable catheter (microdialysis catheter). We inserted such a catheter in to each liver studied, whilst the graft was still in cold storage and in addition the process was repeated once the liver graft was transplanted in the recipient and serial samples were collected for analysis. All liver grafts in the two study groups were comparable by other variables.
We discovered, that DCD grafts had higher lactate and lower pyruvate levels compared with DBD liver grafts. The calculated Lactate/Pyruvate ratio (L/P ratio) was significantly higher in the DCD grafts in the cold storage. This suggested severe energy depletion of DCD grafts in the cold storage. The interesting finding was the ability of the DCD grafts to recover and replenish the energy stores, as evident from comparatively similar L/P ratio immediately post reperfusion. Failed liver allografts in this study cohort showed above average L/P ratio (compared with the functioning grafts) and severe glycogen depletion.
MedicalResearch.com: Were any of the findings unexpected?
Answer: In all cellular systems, energy is vital for the survival. The idea of organ preservation is to minimize the energy demand of the cells whilst the organ is without any circulation and hypothermia significantly reduces the metabolic activity within a cell so that the cells could survive without any circulation for a period of time until the blood supply is re-established. Once the cells a exhausted of energy the cells undergo ischemic damage, and this is augmented by reperfusion injury. The energy depletion in DCD grafts was not an unexpected finding, as one would expect these grafts to utilize the intracellular energy stores during the period of donor warm ischemia however there was no evidence to prove this theory. In this regard the findings of our study could be introduced as “Novel”.
MedicalResearch.com: What should clinicians and patients take away from your report?
Answer: The message from this study are primarily for clinicians or researchers, however understanding of these findings by the patients may help researchers to carry out further research. It may be possible that early post transplant poor outcomes of DCD liver grafts are due to energy exhaustion, hence the focus should be on
1) identification of such grafts run out of energy sources, prior to the transplant operation itself so that the adverse outcomes of primary non function or early graft failure and adverse outcomes could be avoided.
2) more importantly it is worthwhile further studying the effects of increased lactic acidosis of DCD grafts and ways of minimizing tissue acidosis. Tissue acidosis is known to be preventive of organ injury when the grafts are in the cold storage and ischemic. Upon reperfusion of grafts increased graft injury occurs by a process called “pH paradox”, and increased lactic acidosis may accentuate this process leading to worse outcomes. Perhaps this calls for alternative ways of organ preservation, going beyond the currently practiced conventional preservation solutions.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Answer: I recommend novel organ preservation techniques and attempts at replenishing the energy stores prior to the organ procurement in the donor or any other modified techniques of organ preservation minimizing the energy depletion of DCD grafts. Machine perfusion and machine preservation and new technological advances made in the field of solid organ transplantation in the recent past, and these new modalities take away the cold ischemic component of organ preservation, whilst continuous perfusion of organs could be performed whilst the organs are in-situ (in the donor) or once they are recovered from the donor (ex-situ). These perfusion systems supply the organs with oxygen rich blood or any other types of fluids, in addition to the basic energy substrates so the metabolism of cells could continue. We have pioneered the technique of normothermic regional perfusion (NRP) which is an in-situ perfusion technique in our center and our results from our study support the use of such techniques. The future research should also investigate other organ preservation techniques, and preservation solutions aimed at minimizing tissue lactic acidosis.
Citation:
Last Updated on August 23, 2014 by Marie Benz MD FAAD