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<https://discovery.ucl.ac.uk/id/eprint/1318134> <http://purl.org/dc/terms/title> "Therapeutic modulation of liver ischaemia reperfusion injury"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/1318134> <http://purl.org/ontology/bibo/abstract> "Liver Ischaemia Reperfusion Injury (IRI) leads to production of reactive oxygen\r\nspecies and cytokines, which affects hepatocellular function following liver resection\r\nand transplantation.\r\nThis thesis examines 2 hypotheses:\r\n1) The role of intravenous glycine in amelioration of liver IRI in a in vivo animal\r\nmodel of partial lobar liver IRI.\r\n2) Does prophylactically administered N-acetylcysteine prevent liver IRI in\r\npatients undergoing elective liver resection.\r\nMaterials and Methods\r\n1) A rabbit model of hepatic lobar IRI was used to evaluate glycine. 3 groups\r\n(n=6) Sham group (laparotomy alone), ischaemia reperfusion (I/R) group (1\r\nhour ischaemia and 6 hours of reperfusion), and glycine I/R group (IV glycine\r\n5 mg/kg prior to the I/R protocol) were used. Portal blood flow, bile flow and\r\nbile was analysed by H1NMR spectroscopy. Hepatic microcirculation,\r\nintracellular tissue oxygenation, serum TNFα, IL-8, ALT, AST were measured\r\nat 1, 2, 4 and 6 hours following reperfusion.\r\n2) A randomised double blind clinical trial was conducted to assess the effect of\r\nNAC on liver IRI following liver resections. The main outcomes were:\r\nmorbidity and mortality, ICAM-1 expression in liver tissue, liver function tests.\r\nPatients were randomised to receive NAC as IV infusion (NACG) or a placebo\r\ngroup (PG) which received 5% dextrose only. Immunohistochemistry for\r\nICAM-1 was carried out on perioperative liver biopsies. Results\r\n1) Glycine normalised the bile flow, reduced phosphatidylcholine shedding,\r\nlactate surge, and stimulated bile acid, pyruvate, glucose and acetoacetate\r\nrelease. Glycine improved portal blood flow, hepatic microcirculation by the\r\n2nd hour, and hepatic intracellular tissue oxygenation by the 4th hour of\r\nreperfusion. Glycine ameliorated serum TNFα at 1, 2 and 4 hours and serum Il-\r\n8, AST and ALT up to 6 hours post reperfusion as compared to the I/R alone\r\ngroup.\r\n2) Of the 43 patients, 15 received NAC, 16 were randomised to the PG, 12 were\r\nexcluded due to inoperable tumours. Serum ALT was reduced in NACG\r\n(p=0.001), while serum ALP was higher in the NACG (p=0.003). ICAM-1\r\nexpression was up-regulated in 6/16 patients in the PG and in 3/15 patients in\r\nNACG. ICAM-1 was down-regulated in 1/15 patients in the NACG and none\r\nin the PG, the difference was not significant.\r\nConclusions\r\n1) Glycine ameliorated liver IRI, improved bile flow and composition.\r\n2) NAC ameliorated parenchymal liver injury and enhanced liver regeneration in\r\npatients undergoing elective liver resection."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/1318134> <http://purl.org/dc/terms/date> "2011-06-28" .
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