Alterations in Mucosal Morphology and Permeability, but No Bacterial or Endotoxin Translocation Takes Place After Intestinal Ischemia and Early Reperfusion in Pigs

Schlichting, Ellen; Grotmol, Tom; Kähler, Hanne; Næss, Oddvar; Steinbakk, Martin; Lyberg, Torstein

doi:10.1097/00024382-199503020-00006

Cited by 6 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The confocal laser scanning fluorescence microscopic pictures in the present study also give evidence for an enhanced paracellular tissue infiltration of FITC‐LPS under hypoxic conditions. However, these findings are somehow in contrast to other studies performed in pigs, showing alterations in mucosal morphology and permeability, but not an enhanced translocation of bacteria or endotoxin after intestinal ischemia and early reperfusion [19]. In our study, there is a clear infiltration of the tissue by fluorescence‐labelled endotoxin under hypoxic conditions.…”

Section: Discussioncontrasting

confidence: 99%

Effect of ischemia on intestinal permeability of lipopolysaccharides

Drewe

Beglinger

Fricker

2001

Eur J Clin Investigation

View full text Add to dashboard Cite

The enteral absorption of endotoxin (lipopolysaccharide, LPS) was studied in vitro and in vivo. The absorption of fluorescence (FITC) labelled LPS was investigated by uptake studies with rabbit jejunal brush-border membrane vesicles (BBMV), the human intestinal cell line Caco-2 and in rats. FITC-LPS from Salmonella typhimurium was taken up into BBMV in a dose-dependent manner. Uptake was neither pH- nor Na+-dependent, nor could it be inhibited by unlabelled LPS. 74.5% of vesicle-associated fluorescence was due to adhesion to the vesicular membranes, 25.5% was taken up into an osmotically-sensitive space. Transport of LPS across Caco-2 cell monolayers was dose-dependent. The permeation rate increased significantly under ischemic conditions, i.e. when the cells were incubated under oxygen-depleted conditions. However, no significant differences in transepithelial electrical resistances were observed between oxygen depleted and control cells. The release of lactate dehydrogenase was only marginally different from control cells, indicating cell integrity. In situ, after gut ischemia, a significantly increased uptake of fluorescent LPS was observed by fluorescence laser scanning microscopy. Conclusion LPS is taken up by the intestinal mucosa, predominantly by passive transcellular diffusion. Under ischemic conditions, the permeability of LPS is increased mainly by an enhanced paracellular permeability and epithelial destruction. The findings partly explain the clinically observed development of multiorgan system failure after temporary malperfusion of the gut during major vascular surgery or thromboembolism.

show abstract

Section: Discussioncontrasting

confidence: 99%

Effect of ischemia on intestinal permeability of lipopolysaccharides

Drewe

Beglinger

Fricker

2001

Eur J Clin Investigation

View full text Add to dashboard Cite

show abstract

“…Endotoxin may induce shock, but there is no conclusive evidence that endotoxin translocation under experimental conditions serves as the main mechanism for inflammation (27,28). The current evidence suggests that in addition to endotoxins, there are alternative mediators for cell activation.…”

Section: Discussionmentioning

confidence: 90%

Generation of in vivo activating factors in the ischemic intestine by pancreatic enzymes

Mitsuoka

Kistler

Schmid‐Schönbein

2000

Proc. Natl. Acad. Sci. U.S.A.

101

View full text Add to dashboard Cite

One of the early events in physiological shock is the generation of activators for leukocytes, endothelial cells, and other cells in the cardiovascular system. The mechanism by which these activators are produced has remained unresolved. We examine here the hypothesis that pancreatic digestive enzymes in the ischemic intestine may be involved in the generation of activators during intestinal ischemia. The lumen of the small intestine of rats was continuously perfused with saline containing a broadly acting pancreatic enzyme inhibitor (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfate, 0.37 mM) before and during ischemia of the small intestine by splanchnic artery occlusion. This procedure inhibited activation of circulating leukocytes during occlusion and reperfusion. It also prevented the appearance of activators in portal venous and systemic artery plasma and attenuated initiating symptoms of multiple organ injury in shock. Intestinal tissue produces only low levels of activators in the absence of pancreatic enzymes, whereas in the presence of enzymes, activators are produced in a concentration-and time-dependent fashion. The results indicate that pancreatic digestive enzymes in the ischemic intestine serve as an important source for cell activation and inflammation, as well as multiple organ failure.rat ͉ splanchnic arterial occlusion ͉ shock ͉ multiple organ failure ͉ microcirculation S hock is a life-threatening cardiovascular complication (1). Cellular activation in the circulation is a relatively early event in shock that can be detected by leukocyte or endothelial superoxide production, pseudopod projection, expression of membrane adhesion molecules, and many other cell functions (2, 3). Cell activation fundamentally alters the biomechanics of microvascular blood flow by a shift in rheological, adhesive, and cytotoxic cell properties. The interaction between activated leukocytes and endothelial cells is followed by cell and organ failure (4). The level of activation correlates with survival after the shock (5), but the mechanism for production and the source of activating factors has remained an unresolved problem. Several candidates have been proposed, including endotoxins, lipid-derived products, and cytokines (6-9).Recently, we have demonstrated that the supernatant of the homogenized pancreas, but less so homogenates of other organs, mediates a powerful activation of cardiovascular cells (10). Incubation of homogenates from nonactivating organs, such as the liver or intestine, with low concentration of serine proteases also increases the ability to activate leukocytes. An enzyme inhibitor could block the activation, suggesting that pancreatic enzymes may play a central role in the production of activating factors.Pancreatic enzymes are discharged via the pancreatic duct into the duodenum and intestine as a requirement for digestion. We hypothesize that pancreatic enzymes in the ischemic intestine may be involved in the production of activating factors for circulatory cells in shock. Ischemia ...

show abstract

“…Translocation of gut derived bacteria and endotoxin across an ischaemia induced hyperpermeable intestinal barrier has been suggested as an aetiology of multiple organ dysfunction syndrome 78However, some studies have failed to show translocation in shock and the concept of translocation as a main promoter of multiple organ dysfunction syndrome is still under debate 9. Tissue damage by gut derived activated neutrophils has been suggested as an alternative aetiology 10.…”

mentioning

confidence: 99%

The endothelin receptor antagonist bosentan restores gut oxygen delivery and reverses intestinal mucosal acidosis in porcine endotoxin shock

Oldner

Wanecek

Goiny

et al. 1998

Gut

View full text Add to dashboard Cite

Background-Endothelin-1, the most potent vasoconstrictor known, is produced in septic states and may be involved in the pathophysiology of the deteriorated splanchnic circulation seen in septic shock. Aims-To elucidate the capability of bosentan, a non-peptide mixed endothelin receptor antagonist, to attenuate splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in endotoxic shock. Methods-In 16 anaesthetised pigs, central and regional haemodynamics were monitored by thermodilution and ultrasonic flow probes, respectively. A tonometer in the ileum was used for measurement of mucosal pH. Onset of endotoxin challenge was followed by bosentan administration (to eight pigs) two hours later. Results-Endotoxin infusion reduced cardiac index and systemic oxygen delivery; bosentan restored these parameters. The reduced mean arterial blood pressure and renal blood flow remained unaVected by bosentan. The profound reduction in gut oxygen delivery in response to endotoxin was completely abolished by bosentan. Bosentan significantly improved the notably deteriorated intestinal mucosal pH and mucosal-arterial PCO 2 gap. The mucosal-portal vein PCO 2 gap, used to monitor the mucosa in relation to the gut as a whole (including the spleen and pancreas), was also greatly increased by endotoxaemia and significantly reversed by bosentan. Conclusion-Bosentan completely restored the profound endotoxin induced reductions in systemic and gut oxygen delivery with a concomitant reversal of intestinal mucosal acidosis. Results suggest that endothelin is involved in the pronounced perfusion disturbances seen in the gut in endotoxic shock. Bosentan may prove useful in reducing gut ischaemia in septic shock. (Gut 1998;42:696-702)

show abstract

Alterations in Mucosal Morphology and Permeability, but No Bacterial or Endotoxin Translocation Takes Place After Intestinal Ischemia and Early Reperfusion in Pigs

Cited by 6 publications

References 0 publications

Effect of ischemia on intestinal permeability of lipopolysaccharides

Effect of ischemia on intestinal permeability of lipopolysaccharides

Generation of in vivo activating factors in the ischemic intestine by pancreatic enzymes

The endothelin receptor antagonist bosentan restores gut oxygen delivery and reverses intestinal mucosal acidosis in porcine endotoxin shock

Contact Info

Product

Resources

About