TY - JOUR
T1 - The Effects of Heparan Sulfate Infusion on Endothelial and Organ Injury in a Rat Pneumosepsis Model
AU - van den Brink, Daan P.
AU - Kleinveld, Derek J.B.
AU - Bongers, Annabel
AU - Vos, Jaël
AU - Roelofs, Joris T.H.
AU - Weber, Nina C.
AU - van Buul, Jaap D.
AU - Juffermans, Nicole P.
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/10/10
Y1 - 2023/10/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85175372750&partnerID=8YFLogxK
U2 - 10.3390/jcm12206438
DO - 10.3390/jcm12206438
M3 - Article
C2 - 37892576
AN - SCOPUS:85175372750
SN - 2077-0383
VL - 12
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 20
M1 - 6438
ER -