{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:33:51Z","timestamp":1780533231814,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Octapharma AG (Lachen, Switzerland)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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\u2019s 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\u2013105.3] vs. 87.1 CI [68.9\u2013139.3] \u00b5g\/mL, p = 0.76). Similarly, albumin supplemented with HS did not reduce pulmonary FITC-dextran leakage compared to albumin (120.0 [93.8\u2013141.2] vs. 116.2 [61.7 vs. 160.8] \u00b5g\/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.<\/jats:p>","DOI":"10.3390\/jcm12206438","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T06:14:04Z","timestamp":1696918444000},"page":"6438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Effects of Heparan Sulfate Infusion on Endothelial and Organ Injury in a Rat Pneumosepsis Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0552-3225","authenticated-orcid":false,"given":"Daan","family":"van den Brink","sequence":"first","affiliation":[{"name":"Amsterdam UMC, Department of Intensive Care Medicine, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6357-1471","authenticated-orcid":false,"given":"Derek","family":"Kleinveld","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Erasmus MC, Department Anesthesiology, Erasmus University of Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel","family":"Bongers","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ja\u00ebl","family":"Vos","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9595-6571","authenticated-orcid":false,"given":"Joris","family":"Roelofs","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Department of Pathology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam UMC, Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1111-9042","authenticated-orcid":false,"given":"Nina","family":"Weber","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam UMC, Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0054-7949","authenticated-orcid":false,"given":"Jaap","family":"van Buul","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Molecular Cell Biology Laboratory, Department Molecular Hematology, 1066 CX Amsterdam, The Netherlands"},{"name":"Leeuwenhoek Centre for Advanced Microscopy (LCAM), Section Molecular Cytology at Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Juffermans","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Erasmus MC, Department of Intensive Care, Erasmus University of Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s13054-019-2478-6","article-title":"Frequency and mortality of septic shock in Europe and North America: A systematic review and meta-analysis","volume":"23","author":"Vincent","year":"2019","journal-title":"Crit. 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