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  • Title: Post-ischaemic restituted intestinal mucosa is more resistant to further ischaemia than normal mucosa in the pig.
    Author: Juel IS, Solligård E, Tvedt KE, Skogvoll E, Jynge P, Beisvag V, Erlandsen SE, Sandvik AK, Aadahl P, Grønbech JE.
    Journal: Scand J Clin Lab Invest; 2008; 68(2):106-16. PubMed ID: 17852833.
    Abstract:
    OBJECTIVE: Ischaemic preconditioning may protect the intestine from subsequent prolonged ischaemia. This study evaluates whether a much longer initial ischaemia, encountered clinically, may modify intestinal resistance to further ischaemia in a pig model. MATERIAL AND METHODS: After cross-clamping of the superior mesenteric artery for 1 h, the intestine was either reperfused for 8 h or a second cross-clamping for 1 h was performed at 4 h of reperfusion. Based on microarray analysis of intestinal samples at 1, 4 and 8 h of reperfusion, mRNA of selected genes was measured with QRT-PCR. RESULTS: The first ischaemic period caused exfoliation of surface epithelial cells from the basement membrane comprising about 90 % of the villi tips, a marked increase in permeability and depletion of ATP. The second ischaemic challenge caused about 30 % less denudation of the basement membrane (p = 0.008), no increase in permeability (p = 0.008) and less depletion of ATP (p = 0.039). mRNAs for superoxide dismutase 2, heat shock proteins and signal transducer and activator of transcription 3, which may protect against ischaemia/reperfusion injury, were up-regulated throughout the reperfusion period. mRNAs for matrix metalloproteinase 1, connexin 43 and peripheral myelin 22, which may be associated with cell migration or tight junctions, showed a particular up-regulation at 4 h of reperfusion. CONCLUSION: One hour of initial ischaemia followed by 4 h of reperfusion is associated with increased intestinal resistance to further ischaemia. The differential regulation of genes identified in this study provides working hypotheses for mechanisms behind this observation.
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