Vejchapipat, Paisarn; (2001) Intestinal and hepatic metabolism after intestinal ischaemia-reperfusion. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Intestinal ischaemia-reperfusion is a life-threatening situation in infants, children and adults. Conditions associated with intestinal ischaemia-reperfusion include midgut volvulus, intussusception, necrotising enterocolitis, acute mesenteric arterial occlusion, haemodynamic shock and sepsis. Hepatic failure is common after intestinal ischaemia-reperfusion. A rat model of intestinal ischaemia-reperfusion was used throughout. Intestinal and hepatic metabolism were investigated in various experiments using magnetic resonance spectroscopy. Firstly, 90 minutes of intestinal ischaemia followed by 60 minutes of reperfusion resulted in high mortality. It also caused intestinal and hepatic energy failure as indicated by significant impairment in phosphoenergetic status of small intestine and liver. Amino acid metabolism was also affected in both organs: intestinal glutamine, glutamate and alanine increased while hepatic glutamine decreased after intestinal reperfusion. Secondly, the hepatic ATP and inorganic phosphate were continuously monitored during intestinal ischaemia-reperfusion, and this demonstrated the occurrence of hepatic energy failure during reperfusion. Additionally, induction of moderate hypothermia (30-32°C) was found to ameliorate the hepatic energy failure and prevent mortality, but did not attenuate intestinal energy failure. However, moderate hypothermia did attenuate both intestinal and hepatic energy failure after intestinal ischaemia-reperfusion when the ischaemic time was shortened to 60 minutes. Lowering body temperature to 32°C for 2 hours did not affect the phosphoenergetics of small intestine or liver in sham operated rats. Finally, in the model of 30 minutes of intestinal ischaemia followed by 60 minutes of reperfusion, the effects of extraluminal oxygenated perfluorocarbon administration and moderate hypothermia were tested. Although hypothermia ameliorated the energy failure and histological damage to the small intestine, the application of perfluorocarbon during intestinal ischaemia failed to show any beneficial effects on intestinal energy metabolism except a decrease in intestinal lactate level. In conclusion, intestinal ischaemia-reperfusion perturbed intestinal and hepatic energy metabolism. Moderate hypothermia significantly reduced the severity of intestinal ischaemia-reperfusion injury.

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