Chronic morpho-functional damage as a consequence of transient ischemia-reperfusion injury of the small bowel

Abstract

Introduction: The prevailing notion is thatischemia reperfusion injury of the small bowel inducestransient changes that resolve within a few days post-occurrence. However, chronic injury has been describedfollowing a single ischemia reperfusion in the kidney.We proceeded to ascertain if a similar outcome is alsowitnessed in the small bowel. Materials and methods:ACI rats (n=32) underwent 1, 2 or 3 episodes ofischemia reperfusion by clamping the superiormesenteric artery for 45 minutes at 7-day intervals.Control groups included sham-operated (n=6) or non-operated (n=5) rats. Morphology was examined at dayninety post-ischemia reperfusion and immunostainingwas used to evaluate macrophage infiltration,microvascular distribution, and apoptosis. RT-PCR wasused to evaluate expression of Inter-Cellular AdhesionMolecule-1 (ICAM-1), transforming growth factor-ß(TGF-ß), Insulin Growth Factor-I (IGF-1), and InsulinGrowth Factor-I Receptor (IGF-R). Intestinal functionwas evaluated by D-xylose performed 24 hours and 4, 8,and 12 weeks after reperfusion. Results: Chronicmorphologic changes were observed with degenerationof crypts, endothelial damage, matrix degeneration, andheightened lymphocyte degeneration within the Payer’spatches. Major structural changes were characterized byvillous atrophy from partial to total. The grade ofhistological injuries was significantly increased(P<0.001) after multiple ischemia reperfusion episodes.A higher number of apoptotic cells (P<0.001) and aprominent macrophage infiltration (P<0.05) was alsowitnessed. Altered expression of ICAM-1, TGF-ß, andIGF-1 was observed. At 24 hours after ischemiareperfusion D-xylose absorption was diminished,returning to baseline values within 4 weeks and becoming abnormal again at 8 and 12 weeks (P<0.05).CONCLUSIONS: Unlike the prevailing conviction,these data demonstrate that transient ischemiareperfusion repeated injuries of the small bowel result inchronic intestinal damage.