Chronic morpho-functional damage as a consequence of transient ischemia/reperfusion injury of the small bowel
Sergio Morini1, Georg Elias2, Melisa Brown2, Vladimir Subbotin3, Cristiana Rastellini4 and Luca Cicalese4
1Department of Biomedical Research (CIR), University Campus Bio Medico, Rome, Italy, 2Division of Transplantation, Department of Surgery, University of Massachusetts, Worcester, MA, USA, 3Mirus Bio Corporation, Madison, WI, USA and 4Division of Transplantation, Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.
Offprint requests to: Luca Cicalese MD, General Surgery and Transplant Service, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555-0533, USA. e-mail: email@example.com
Summary. Introduction: The prevailing notion is that ischemia reperfusion injury of the small bowel induces transient changes that resolve within a few days post-occurrence. However, chronic injury has been described following a single ischemia reperfusion in the kidney. We proceeded to ascertain if a similar outcome is also witnessed in the small bowel. Materials and methods: ACI rats (n=32) underwent 1, 2 or 3 episodes of ischemia reperfusion by clamping the superior mesenteric 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 day ninety post-ischemia reperfusion and immunostaining was used to evaluate macrophage infiltration, microvascular distribution, and apoptosis. RT-PCR was used to evaluate expression of Inter-Cellular Adhesion Molecule-1 (ICAM-1), transforming growth factor-ß (TGF-ß), Insulin Growth Factor-I (IGF-1), and Insulin Growth Factor-I Receptor (IGF-R). Intestinal function was evaluated by D-xylose performed 24 hours and 4, 8, and 12 weeks after reperfusion. Results: Chronic morphologic changes were observed with degeneration of crypts, endothelial damage, matrix degeneration, and heightened lymphocyte degeneration within the Payer’s patches. Major structural changes were characterized by villous atrophy from partial to total. The grade of histological injuries was significantly increased (P<0.001) after multiple ischemia reperfusion episodes. A higher number of apoptotic cells (P<0.001) and a prominent macrophage infiltration (P<0.05) was also witnessed. Altered expression of ICAM-1, TGF-ß, and IGF-1 was observed. At 24 hours after ischemia reperfusion 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 ischemia reperfusion repeated injuries of the small bowel result in chronic intestinal damage. Histol Histopathol 25, 277-286 (2010)
Key words: Chronic intestinal injury, Intestinal transient ischemia, Transient ischemia/reperfusion, Small bowel, Intestine