Abstract
BackgroundRecently, we observed that small-intestinal ischemia and reperfusion was found to entail a rapid loss of apoptotic and necrotic cells. This study was conducted to investigate whether the observed shedding of ischemically damaged epithelial cells affects IR induced inflammation in the human small gut.Methods and FindingsUsing a newly developed IR model of the human small intestine, the inflammatory response was studied on cellular, protein and mRNA level. Thirty patients were consecutively included. Part of the jejunum was subjected to 30 minutes of ischemia and variable reperfusion periods (mean reperfusion time 120 (±11) minutes). Ethical approval and informed consent were obtained. Increased plasma intestinal fatty acid binding protein (I-FABP) levels indicated loss in epithelial cell integrity in response to ischemia and reperfusion (p<0.001 vs healthy). HIF-1α gene expression doubled (p = 0.02) and C3 gene expression increased 4-fold (p = 0.01) over the course of IR. Gut barrier failure, assessed as LPS concentration in small bowel venous effluent blood, was not observed (p = 0.18). Additionally, mRNA expression of HO-1, IL-6, IL-8 did not alter. No increased expression of endothelial adhesion molecules, TNFα release, increased numbers of inflammatory cells (p = 0.71) or complement activation, assessed as activated C3 (p = 0.14), were detected in the reperfused tissue.ConclusionsIn the human small intestine, thirty minutes of ischemia followed by up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory response. This may be explained by a unique mechanism of shedding of damaged enterocytes, reported for the first time by our group.
Highlights
We demonstrated the ability of the human small intestine to rapidly restore its epithelial architecture after massive epithelial sloughing and gut barrier damage in response to a thirty minutes ischemic episode and variable reperfusion periods.[1]
In the human small intestine, thirty minutes of ischemia followed by up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory response. This may be explained by a unique mechanism of shedding of damaged enterocytes, reported for the first time by our group
Intestinal epithelial damage Epithelial cell integrity was lost in response to 30 minutes of ischemia followed by various periods of reperfusion
Summary
We demonstrated the ability of the human small intestine to rapidly restore its epithelial architecture after massive epithelial sloughing and gut barrier damage in response to a thirty minutes ischemic episode and variable reperfusion periods.[1]. The presence of apoptosis or cellular damage in reperfused ischemic organs has cardinal implications in the pathogenesis of ischemia reperfusion (IR).[2,3] Massive apoptosis and subsequent necrosis are involved in the induction of inflammation after organ ischemia This notion is based on the observation that therapeutic strategies aimed at preventing IR induced apoptosis can ameliorate IR induced inflammation.[4,5,6,7] Numerous experimental studies have shown that the inflammatory response following IR mediates the development of additional reperfusion injury, further compromising organ function.[4,8,9,10,11,12] Different strategies aimed at preventing IR induced inflammation can effectively reduce organ damage.[13]. This study was conducted to investigate whether the observed shedding of ischemically damaged epithelial cells affects IR induced inflammation in the human small gut
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