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• W199228220 abstract "Liver Ischaemia Reperfusion Injury (IRI) leads to production of reactive oxygenspecies and cytokines, which affects hepatocellular function following liver resectionand transplantation.This thesis examines 2 hypotheses:1) The role of intravenous glycine in amelioration of liver IRI in a in vivo animalmodel of partial lobar liver IRI.2) Does prophylactically administered N-acetylcysteine prevent liver IRI inpatients undergoing elective liver resection.Materials and Methods1) A rabbit model of hepatic lobar IRI was used to evaluate glycine. 3 groups(n=6) Sham group (laparotomy alone), ischaemia reperfusion (I/R) group (1hour ischaemia and 6 hours of reperfusion), and glycine I/R group (IV glycine5 mg/kg prior to the I/R protocol) were used. Portal blood flow, bile flow andbile was analysed by H1NMR spectroscopy. Hepatic microcirculation,intracellular tissue oxygenation, serum TNFα, IL-8, ALT, AST were measuredat 1, 2, 4 and 6 hours following reperfusion.2) A randomised double blind clinical trial was conducted to assess the effect ofNAC on liver IRI following liver resections. The main outcomes were:morbidity and mortality, ICAM-1 expression in liver tissue, liver function tests.Patients were randomised to receive NAC as IV infusion (NACG) or a placebogroup (PG) which received 5% dextrose only. Immunohistochemistry forICAM-1 was carried out on perioperative liver biopsies. Results1) Glycine normalised the bile flow, reduced phosphatidylcholine shedding,lactate surge, and stimulated bile acid, pyruvate, glucose and acetoacetaterelease. Glycine improved portal blood flow, hepatic microcirculation by the2nd hour, and hepatic intracellular tissue oxygenation by the 4th hour ofreperfusion. Glycine ameliorated serum TNFα at 1, 2 and 4 hours and serum Il-8, AST and ALT up to 6 hours post reperfusion as compared to the I/R alonegroup.2) Of the 43 patients, 15 received NAC, 16 were randomised to the PG, 12 wereexcluded due to inoperable tumours. Serum ALT was reduced in NACG(p=0.001), while serum ALP was higher in the NACG (p=0.003). ICAM-1expression was up-regulated in 6/16 patients in the PG and in 3/15 patients inNACG. ICAM-1 was down-regulated in 1/15 patients in the NACG and nonein the PG, the difference was not significant.Conclusions1) Glycine ameliorated liver IRI, improved bile flow and composition.2) NAC ameliorated parenchymal liver injury and enhanced liver regeneration inpatients undergoing elective liver resection." @default.
• W199228220 created "2016-06-24" @default.
• W199228220 creator A5004787334 @default.
• W199228220 date "2011-06-28" @default.
• W199228220 modified "2023-09-24" @default.
• W199228220 title "Therapeutic modulation of liver ischaemia reperfusion injury" @default.
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