Propofol has been shown to against intestinal reperfusion injury when treated either before or after ischemia, during which mast cell could be activated. The aim of this study was to evaluate the role of propofol in restoring the intestinal epithelial cells integrity disrupted by mast cell activation or the released tryptase after activation in vitro. We investigated the effect of: (1) tryptase on Caco-2 monolayers in the presence of PAR-2 inhibitor or propofol, (2) mast cell degranulation in a Caco-2/LAD-2 co-culture model in the presence of propofol, and (3) propofol on mast cell degranulation. Epithelial integrity was detected using transepithelial resistance (TER) and permeability to fluorescein isothiocyanate (FITC)-dextran (the apparent permeability coefficient, Papp). The expression of junctional proteins zonula occludens-1 (ZO-1/TJP1) and occludin were determined using western blot analysis and immunofluorescence microscopy. The intracellular levels of reactive oxidative species (ROS) and Ca2+ were measured using flow cytometry. Tryptase directly enhanced intestinal barrier permeability as demonstrated by significant reductions in TER, ZO-1, and occludin protein expression and concomitant increases in Papp. The intestinal barrier integrity was restored by PAR-2 inhibitor but not by propofol. Meanwhile, mast cell degranulation resulted in epithelial integrity disruption in the Caco-2/LAD-2 co-culture model, which was dramatically attenuated by propofol. Mast cell degranulation caused significant increases in intracellular ROS and Ca2+ levels, which were blocked by propofol and NAC. Propofol pretreatment can inhibit mast cell activation via ROS/Ca2+ and restore the intestinal barrier integrity induced by mast cell activation, instead of by tryptase.
Hemorrhagic shock (HS) represents an acute event with high mortality. The optimal combination of anesthetics that would prevent hemodynamic collapse and allow damage control surgery has not yet been determined. We tested the hypothesis that a combination of dissociative anesthetic ketamine with alpha2- agonist medetomidine (MK group, n=10) would provide superior hemodynamic control compared to propofol-remifentanil (PR group, n=10) during HS in minipigs. A modified Wiggers‘ model of HS with a target mean arterial pressure (MAP) of 40 mm Hg and 2 h duration was used. All minipigs survived. HS led to a ~50 % decrease in cardiac output in both groups (P<0.001 for baseline vs. HS 120 min) with no differences between groups. Total volume of removed blood was larger in the MK group (1321±133 ml vs. 1111±246 ml in the PR group, respectively; P<0.05). MAP was higher during the initial phases of HS in the MK group than in PR group (P<0.05 at HS 30-90 min). HR was lower in the MK group at the late phases of HS (P<0.05 at HS 60-120 min). In conclusion, medetomidine-ketamine provides a feasible and possibly a more favorable alternative to the propofol-remifentanil combination in our model of HS in minipigs., A. Brezina ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy