The use of microdialysis and metabolomics to study the biomarker differences between donation after circulatory death (DCD) and donation after brain death (DBD) liver grafts in orthotopic liver transplantation

Perera, Thamara Prabhath Ranasinghe (2015). The use of microdialysis and metabolomics to study the biomarker differences between donation after circulatory death (DCD) and donation after brain death (DBD) liver grafts in orthotopic liver transplantation. University of Birmingham. M.D.

Preview

Perera15MD_Redacted.pdf
PDF - Redacted Version
Download (2MB)

Abstract

Donor organ shortage is a major barrier to the progress of liver transplantation; options to widen the donor pool include use of marginal donor grafts and those from donors after circulatory death (DCD), despite risks of early graft failure. This thesis studies the key metabolic feature differences between DCD and from donors after brain death (DBD), using combination of microdialysis for tissue fluid sampling, and colourimetry, Coularray and Fourier Transform ion Cyclotron Resistance - mass spectrometry(FTICR-MS) as analytical platforms. The initial study proved feasibility of above methods to identify metabolic changes through cold storage to reperfusion, and the involvement of energy and amino acid metabolism pathways. Comparison of DCD and DBD grafts by microdialysis combined with colourimetry proved energy depletion, and increased lactate/pyruvate ratio in DCD grafts. Metabolomic studies consolidated the findings of primary impact on energy metabolism pathways during cold storage. Both CEAD and FTICR-MS identified key biomarker differences and the effect on tryptophan and kynurenine pathway, and this finding was reproduced in all three metabolomic studies conducted. Over expression of these metabolites in DCD grafts and failed allografts may be related to energy metabolism, and tryptophan and kynurenine could potentially be developed as biomarkers predicting liver graft function.

Type of Work:

Thesis (Higher Doctorates > M.D.)

Award Type:

Higher Doctorates > M.D.

Supervisor(s):