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Introduction: Alteration in endothelial function during sepsis is thought to play a key role in the progression of organ failure. We herein compared plasma concentrations of endothelial activation biomarkers vascular endothelial growth factor (VEGF), hyaluronan (HA), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF), as well as inflammatory mediator concentrations (IL-6, IL-8, IL-10, C-reactive protein and monocyte chemoattractant protein-1) in dogs with sepsis to healthy dogs. Methods: This study was a multicenter observational clinical trial conducted at two university teaching hospitals from February 2016 until July 2017. The study included 18 client-owned dogs hospitalized with sepsis and at least one distant organ dysfunction, as well as 20 healthy dogs. Plasma biomarker concentrations were measured using ELISA. Severity of illness in dogs with sepsis was calculated using the 5-variable acute physiologic and laboratory evaluation (APPLEFAST) score. Biomarker concentrations were compared between septic and healthy dogs using linear models. Results: Septic peritonitis was the most frequent source of sepsis (11/18; 61%), followed by pneumonia (4/18; 22%). Ten dogs (56%) had only 1 organ dysfunction, whereas 3 dogs (17%) had 2, 3 (17%) had 3, 1 (6%) had 4 and 1 (6%) had 5 organ dysfunctions. The median APPLEFAST score in the septic dogs was 28.5 (Q1-Q3, 24-31). Mean plasma concentrations of all endothelial and inflammatory biomarkers, except vWF, were higher in the sepsis cohort than in controls. The mean endothelial biomarker concentrations in the septic cohort ranged from ~2.7-fold higher for HA (difference in means; 118.2 ng/mL, 95% credible limit; 44.5-221.7) to ~150-fold for VEGF (difference in means; 76.6 pg./mL, 95% credible limit; 33.0-143.4), compared to the healthy cohort. Fifteen dogs with sepsis (83%) died; 7 (46%) were euthanized and 8 (53%) died during hospitalization. Conclusion: Dogs with naturally occurring sepsis and organ dysfunction had higher mean concentrations of biomarkers of endothelial activation and inflammation compared to healthy dogs, broadening our understanding of the pathophysiology of sepsis secondary to endothelial dysfunction.
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OBJECTIVE: To conduct a narrative review of the current literature in reference to the structure and function of the endothelial glycocalyx (EG) and its contribution to the pathophysiology of conditions relevant to the veterinary emergency and critical care clinician. Novel therapies for restoring or preserving the EG will also be discussed. DATA SOURCES: Online databases (PubMed, CAB abstracts, Scopus) were searched between January 1st 2017 and May 1st 2017 for English language articles without publication date restriction. Keywords included EG, endothelial surface layer, degradation, syndecan-1, heparan sulfate, critical illness, sepsis, trauma, and therapeutics. DATA SYNTHESIS: The EG is a complex and important structure located on the luminal surface of all blood vessels throughout the body. It plays an important role in normal vascular homeostasis including control of fluid exchange across the vascular barrier. Loss or degradation of the EG has an impact on inflammation, coagulation, and vascular permeability and tone. These changes are essential components in the pathophysiology of many conditions including sepsis and trauma. A substantial body of experimental animal and human clinical research over the last decade has demonstrated increased circulating concentrations of EG degradation products in these conditions. However, veterinary-specific research into the EG and critical illness is currently lacking. The utility of EG degradation products as diagnostic and prognostic tools continues to be investigated and new therapies to preserve or improve EG structure and function are under development. CONCLUSIONS: The recognition of the presence of the EG has changed our understanding of transvascular fluid flux and the pathophysiology of many conditions of critical illness. The EG is an exciting target for novel therapeutics to improve morbidity and mortality in conditions such as sepsis and trauma.
