| Autor: |
van den Brink DP; Amsterdam UMC, Department of Intensive Care Medicine, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands., Kleinveld DJB; Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Erasmus MC, Department Anesthesiology, Erasmus University of Rotterdam, 3015 GD Rotterdam, The Netherlands., Bongers A; Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands., Vos J; Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands., Roelofs JJTH; Amsterdam UMC, Department of Pathology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Amsterdam UMC, Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands., Weber NC; Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Amsterdam UMC, Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands., van Buul JD; Sanquin Research and Landsteiner Laboratory, Molecular Cell Biology Laboratory, Department Molecular Hematology, 1066 CX Amsterdam, The Netherlands.; Leeuwenhoek Centre for Advanced Microscopy (LCAM), Section Molecular Cytology at Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, 1066 CX Amsterdam, The Netherlands., Juffermans NP; Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Erasmus MC, Department of Intensive Care, Erasmus University of Rotterdam, 3015 GD Rotterdam, The Netherlands. |
| Abstrakt: |
Septic shock is characterized by endothelial dysfunction, leading to tissue edema and organ failure. Heparan sulfate (HS) is essential for vascular barrier integrity, possibly via albumin as a carrier. We hypothesized that supplementing fluid resuscitation with HS would improve endothelial barrier function, thereby reducing organ edema and injury in a rat pneumosepsis model. Following intratracheal inoculation with Streptococcus pneumoniae, Sprague Dawley rats were randomized to resuscitation with a fixed volume of either Ringer's Lactate (RL, standard of care), RL supplemented with 7 mg/kg HS, 5% human albumin, or 5% human albumin supplemented with 7 mg/kg HS ( n = 11 per group). Controls were sham inoculated animals. Five hours after the start of resuscitation, animals were sacrificed. To assess endothelial permeability, 70 kD FITC-labelled dextran was administered before sacrifice. Blood samples were taken to assess markers of endothelial and organ injury. Organs were harvested to quantify pulmonary FITC-dextran leakage, organ edema, and for histology. Inoculation resulted in sepsis, with increased lactate levels, pulmonary FITC-dextran leakage, pulmonary edema, and pulmonary histologic injury scores compared to healthy controls. RL supplemented with HS did not reduce median pulmonary FITC-dextran leakage compared to RL alone (95.1 CI [62.0-105.3] vs. 87.1 CI [68.9-139.3] µg/mL, p = 0.76). Similarly, albumin supplemented with HS did not reduce pulmonary FITC-dextran leakage compared to albumin (120.0 [93.8-141.2] vs. 116.2 [61.7 vs. 160.8] µg/mL, p = 0.86). No differences were found in organ injury between groups. Heparan sulfate, as an add-on therapy to RL or albumin resuscitation, did not reduce organ or endothelial injury in a rat pneumosepsis model. Higher doses of heparan sulfate may decrease organ and endothelial injury induced by shock. |
