El-Wahsh, Mohamed Mohamed Zaki Mohamed; (2002) The effect of donor liver organ preservation and reperfusion techniques on the expression of cellular adhesion molecules. Doctoral thesis (Ph.D), UCL (University College London).

Text out.pdf Download (11MB)

Abstract

Ischaemia/reperfusion (I/R) injury has a major influence on the outcome of liver transplantation. The cell adhesion molecule ICAM-1 has a central role in the interaction between polymorphonuclear neutrophils (PMNs) and sinusoidal endothelial cells (SEC's) which is fundamental to the development of I/R injury. This thesis has investigated the effect of liver preservation and reperfusion on ICAM-1 expression in both animal experimental models and human liver transplantation. Factors which are likely to induce ICAM-1 were analysed including endotoxic shock, warm and cold ischaemia and I/R injury using an animal model of lobar I/R and an isolated perfused liver circuit. In the rat model of endotoxaemia ICAM-1 expression was markedly induced. Warm ischaemia for periods up to 45 minutes or cold ischaemia up to 8 hours did not induce ICAM-1 expression on the sinusoidal endothelium but it was markedly induced with longer periods. ICAM-1 expression was found to correlate with biochemical evidence of hepatocyte damage (ALT & AST levels) and histological changes in the liver. I/R injury had a more marked effect on ICAM-1 expression than ischaemia alone. ICAM-1 expression was also induced in the non ischaemic liver lobe. The influence of adhesion molecule induction on the liver microcirculation was investigated in vivo using laser Doppler flowmetry. Increased SEC's ICAM-1 expression was directly associated with impairment of the hepatic microcirculation. Adhesion molecule induction is associated with activation of inflammatory cytokines and the formation of oxygen free radicals. The effect of adding the free radical scavenger reduced glutathione (GSH) to the liver perfusate on ICAM-1 expression was investigated in an ex vivo perfused circuit. Isolated rat livers were perfused on bench with oxygenated buffer in a non-recirculating technique. GSH had no significant effect on the histological grading of I/R injury. However, SEC's ICAM-1 expression was significantly reduced in GSH perfused livers with cold ischaemia up to 16 hours but not with 24 hours. The timing and significance of ICAM-1 induction was then investigated in 83 patients undergoing orthotopic liver transplantation (OLT). Liver biopsies were assessed for ICAM-1 and compared with histological evidence of I/R injury, biochemical indicators of early graft function and the incidence of acute cellular rejection. ICAM-1 induction following graft reperfusion was associated with a higher incidence of acute cellular rejection.

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as XMLCSVJSON

Archive Staff Only

View Item