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



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-beta (TGF-beta), 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.



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-beta, 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).



Unlike the prevailing conviction, these data demonstrate that transient ischemia reperfusion repeated injuries of the small bowel result in chronic intestinal damage.
Morini
Sergio
S
Department of Biomedical Research (CIR), University Campus Bio Medico, Rome, Italy.
Elias
Georg
G
Brown
Melisa
M
Subbotin
Vladimir
V
Rastellini
Cristiana
C
Cicalese
Luca
L
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001284:Atrophy / Q000473:pathology; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D016212:Transforming Growth Factor beta; D018799:Intercellular Adhesion Molecule-1; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1