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Rapid reversal of human intestinal ischemia‐reperfusion induced damage by shedding of injured enterocytes and reepithelialisation
Author(s) -
Grootjans Joep,
Derikx Joep PM,
Matthijsen Robert A,
Thuijls Geertje,
Bruïne Adriaan P,
Bijnen Annemarie A,
Dam Ronald M,
Buurman Wim A,
Dejong Cornelis HC
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.235.5
Subject(s) - ischemia , enterocyte , apoptosis , tight junction , reperfusion injury , jejunum , immunohistochemistry , pathology , intestinal mucosa , chemistry , lumen (anatomy) , small intestine , biology , medicine , microbiology and biotechnology , biochemistry
Intestinal ischemia reperfusion (I‐IR) has primarily been studied in animal models whereas human data on I‐IR are scarce. We developed a harmless human experimental model aiming to unravel the sequelae of human small I‐IR. In this model, an isolated part of jejunum, to be removed for surgical reasons, was subjected in vivo to various ischemic periods by vascular clamping, followed by reperfusion. Damage to the intestinal barrier was objectified with immunohistochemistry for morphology (H/E), tight junction proteins (TJ) ZO‐1 and Claudin‐3, apoptosis marker M30, cytokines and neutrophil activation products. To assess epithelial cell damage, arteriovenous (V‐A) concentration differences of Intestinal‐Fatty Acid Binding Protein (I‐FABP) were measured. Jejunal histology revealed the appearance of subepithelial spaces after 30 minutes ischemia (fig 1B, normal tissue: fig 1A) with loss of TJ. Mean (SEM) I‐FABP release significantly increased immediately upon reperfusion (fig 2: 290 (46) to 3997 (554) pg/ml, p<0.001). After 25 minutes reperfusion massive apoptosis and shedding of damaged enterocytes into the lumen was seen (fig 1C). Within 60 minutes of reperfusion the epithelial barrier was fully restored, while debris of apoptotic, shedded enterocytes was found in the lumen (fig 1D). This study revealed a unique gut‐specific mechanism of the reversal of IR‐induced intestinal damage.