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  3. The Effects of Heparan Sulfate Infusion on Endothelial and Organ Injury in a Rat Pneumosepsis Model

The Effects of Heparan Sulfate Infusion on Endothelial and Organ Injury in a Rat Pneumosepsis Model

  • J Clin Med. 2023 Oct 10;12(20):6438. doi: 10.3390/jcm12206438.
Daan P van den Brink 1 2,  Derek J B Kleinveld 2 3,  Annabel Bongers 2,  Jaël Vos 2,  Joris J T H Roelofs 4 5,  Nina C Weber 2 5,  Jaap D van Buul 6 7,  Nicole P Juffermans 2 8
Affiliations

Affiliations

  • 1 Amsterdam UMC, Department of Intensive Care Medicine, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
  • 2 Amsterdam UMC, Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
  • 3 Erasmus MC, Department Anesthesiology, Erasmus University of Rotterdam, 3015 GD Rotterdam, The Netherlands.
  • 4 Amsterdam UMC, Department of Pathology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
  • 5 Amsterdam UMC, Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands.
  • 6 Sanquin Research and Landsteiner Laboratory, Molecular Cell Biology Laboratory, Department Molecular Hematology, 1066 CX Amsterdam, The Netherlands.
  • 7 Leeuwenhoek Centre for Advanced Microscopy (LCAM), Section Molecular Cytology at Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, 1066 CX Amsterdam, The Netherlands.
  • 8 Erasmus MC, Department of Intensive Care, Erasmus University of Rotterdam, 3015 GD Rotterdam, The Netherlands.
PMID: 37892576 DOI: 10.3390/jcm12206438
Abstract

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.

Keywords

animal model; endothelium; heparan sulfate; resuscitation; sepsis; shock.

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