The involvement of multiple protease-antiprotease systems and gut origin sepsis in zymosan-associated endothelial barrier injury and multiple organ dysfunction in rats.

Multiple organ dysfunction syndrome is a dominant cause of mortality in the intensive care unit. Experimentally, a condition similar to the multiple organ dysfunction syndrome can be induced by the intraperitoneal injection of sterile zymosan. In the present study we investigate potential alterations in multiple organ functions, endothelial permeability, and antiproteinases after intraperitoneal injection of zymosan at various doses.

Beneficial effects of lexipafant, a PAF antagonist on gut barrier dysfunction caused by intestinal ischemia and reperfusion in rats.

Background: Platelet-activating factor (PAF) may play a pivotal role in the pathogenesis of intestinal ischemic injury.

Methods: The potential role of PAF in intestinal ischemia and reperfusion (I/R) and the development of gut endothelial and epithelial barrier dysfunction and distant organ injury were investigated by pretreatment with a PAF antagonist, lexipafant. Bidirectional permeability of the intestinal barrier, enteric bacterial translocation, protease-antiprotease balance and mucosal histology, and also changes in pulmonary and liver endothelial barrier permeability were measured following intestinal ischemia for 40 min with 6 h of reperfusion in rats.

Effect of a platelet-activating factor antagonist on pancreatitis-associated gut barrier dysfunction in rats.

Platelet-activating factor (PAF) may play a critical and primary role in the pathogenesis of acute pancreatitis and pancreatitis-associated distant organ injury. The present study evaluated the effect of a PAF antagonist, lexipafant (an (S)-4-methyl-2[methyl-imidazo[4,5-c]pyridin-1-ylmethyl)-benzene sulphonyl]-amino]pentanoic acid ethyl ester, BB-882; British Biotech Ltd.), on the potential prevention of gut barrier dysfunction, by measuring gut origin sepsis, bidirectional permeability of the intestinal barrier, and pancreatic capillary endothelial barrier integrity, in acute pancreatitis induced by intraductal infusion of 5% sodium taurodeoxycholate.

The role of intravenous administration of dextran 70 in enteric bacterial translocation after partial hepatectomy in rats.

The aim of this study was to assess the effect of intravenous dextran on bacterial translocation and intestinal vascular endothelial and epithelial barrier function after experimental partial hepatectomy. We determined systemic arterial pressure, enteric bacterial growth (proximal and distal small intestine and colon) and bacterial translocation (BT) to mesenteric lymph nodes (MLN), liver, lungs, spleen, kidneys and blood, as well as intestinal vascular endothelial and epithelial barrier permeability, after sham operation or partial hepatectomy (50% and 90%) with preoperative intravenous administration of saline, albumin or dextran 70. Subtotal hepatectomy induced a significant decrease in arterial pressure and an increase in the number of Escherichia coli in the distal small intestine.