loading  Checking for direct PDF access through Ovid



In an effort to determine whether treatment with lisofylline (LSF) ameliorates intestinal barrier dysfunction in rats subjected to mesenteric ischemia and reperfusion (I/R), regional mesenteric vessels were occluded for 60 min and then undamped for 60 min more. In Protocol 1, intravenous LSF (15 mg/kg bolus then 10 mg/kg/h) was administered 5 min before ischemia. In Protocol 2, LSF (same dose) was given 1 min before reperfusion. Controls received an equivalent volume of Ringer's lactate solution. Permeability was assessed by determining the mucosal-to-serosal clearance of fluorescein isothiocyanate-conjugated dextran (4 kDa) in everted ileal gut sacs incubated ex vivo. In Protocol 1, LSF treatment during ischemia ameliorated mucosal barrier dysfunction; mean ± SEM clearances for the LSF and Ringer's lactate solution groups after 60 min of ischemia were 34.4 ± 6.1 and 64 ± 7.1 nLAnin/cm2, respectively; p = .007. Clearances after reperfusion were the same in the two groups. In Protocol 2, LSF treatment just before reperfusion ameliorated barrier dysfunction measured 60 min after the restoration of blood flow; clearances for the LSF and Ringer's lactate solution groups were 23.1 ± 3.8 and 40.2 ± 4.5 nL/min/cm2, respectively; p = .012. Treatment with LSF did not affect intestinal levels of reduced glutathione or adenosine triphos-phate or the extent of histological damage to the mucosa after I/R. Nevertheless, villus height was greater in animals treated with LSF than RLS prior to ischemia in Protocol 1 (250 ± 37 and 160 ± 15 μm, respectively; p = .04) and during reperfusion in Protocol 2 (170 ± 21 and 82 ± 7 μm, respectively; p = .002). We conclude that LSF is effective in reducing both ischemia- and I/R-induced gut barrier dysfunction, possibly due to a mechanism related to preservation of villus height.

Related Topics

    loading  Loading Related Articles