Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine

Loss of integrity of the epithelial/mucosal barrier in the small intestine has been associated with different pathologies that originate and/or develop in the gastrointestinal tract. We showed recently that mucin, the main protein in the mucus layer, is disrupted during early periods of intestinal ischemia. This event is accompanied by entry of pancreatic digestive enzymes into the intestinal wall. We hypothesize that the mucin-containing mucus layer is the main barrier preventing digestive enzymes from contacting the epithelium. Mucin breakdown may render the epithelium accessible to pancreatic enzymes, causing its disruption and increased permeability. The objective of this study was to investigate the role of mucin as a protection for epithelial integrity and function. A rat model of 30 min splanchnic arterial occlusion (SAO) was used to study the degradation of two mucin isoforms (mucin 2 and 13) and two epithelial membrane proteins (E-cadherin and toll-like receptor 4, TLR4). In addition, the role of digestive enzymes in mucin breakdown was assessed in this model by luminal inhibition with acarbose, tranexamic acid, or nafamostat mesilate. Furthermore, the protective effect of the mucin layer against trypsin-mediated disruption of the intestinal epithelium was studied in vitro. Rats after SAO showed degradation of mucin 2 and fragmentation of mucin 13, which was not prevented by protease inhibition. Mucin breakdown was accompanied by increased intestinal permeability to FITC-dextran as well as degradation of E-cadherin and TLR4. Addition of mucin to intestinal epithelial cells in vitro protected against trypsin-mediated degradation of E-cadherin and TLR4 and reduced permeability of FITC-dextran across the monolayer. These results indicate that mucin plays an important role in the preservation of the mucosal barrier and that ischemia but not digestive enzymes disturbs mucin integrity, while digestive enzymes actively mediate epithelial cell disruption

Intravenous infusion of propofol for induction and maintenance of anaesthesia during endoscopic carbon dioxide laser ENT procedures with high frequency jet ventilation.

Fourteen patients of ASA grades 1-3 were anaesthetised with continuous infusions of propofol and alfentanil for endoscopic carbon dioxide laser ENT microsurgery. Their lungs were ventilated with an oxygen-air mixture using a high frequency jet ventilator. Propofol was given at an initial rate of 120 micrograms/kg/minute for 10 minutes after a bolus dose of 2.6 mg/kg, and then at 80 micrograms/kg/minute. Alfentanil was given at a rate of 0.5 micrograms/kg/minute. Arterial pressure decreased significantly after the bolus dose. It increased significantly for a few minutes after laryngoscopy and returned to baseline values during maintenance of anaesthesia. Heart rate increased significantly during induction and until laryngoscopy was performed but it decreased below its initial value after 5 minutes of maintenance. Platelet count and the degree of aggregation did not change during infusion of propofol