Use of serum hyaluronic acid as a biomarker of endothelial glycocalyx degradation in dogs with septic peritonitis

Abstract

OBJECTIVE To describe daily changes in serum concentrations of hyaluronic acid (HA), a biomarker of endothelial glycocalyx degradation, in dogs with septic peritonitis and to determine whether relationships exist among serum concentrations of HA and biomarkers of inflammation and patient fluid status. ANIMALS 8 client-owned dogs. PROCEDURES Serum samples that had been collected for a previous study and stored at −80°C were used. Blood samples were collected at admission and daily thereafter during hospitalization and were analyzed for concentrations of HA and interleukins 6, 8, and 10. Patient data including acute patient physiologic and laboratory evaluation score, type and amount of fluids administered daily, and daily CBC and lactate concentration results were recorded. To determine the significant predictors of HA concentration, a general linear mixed model for repeated measures was developed. RESULTS All dogs survived to discharge. Concentrations of HA ranged from 18 to 1,050 ng/mL (interquartile [25th to 75th percentile] range, 49 to 119 ng/mL) throughout hospitalization. Interleukin-6 concentration was a significant predictor of HA concentration as was total administered daily fluid volume when accounting for interleukin-6 concentration. When fluid volume was analyzed independent of inflammatory status, fluid volume was not a significant predictor. Concentrations of HA did not significantly change over time but tended to increase on day 2 or 3 of hospitalization. CONCLUSIONS AND CLINICAL RELEVANCE Results supported the theory that inflammation is associated with endothelial glycocalyx degradation. Dogs recovering from septic peritonitis may become more susceptible to further endothelial glycocalyx damage as increasing fluid volumes are administered.

The microvascular endothelial glycocalyx: An additional piece of the puzzle in veterinary medicine

“…Increases were correlated with increased risk of mortality. Veterinary Species Shaw et al (2021) Septic peritonitis Serum HA Serum HA increased on day 2 or 3 of hospitalization. Interleukin-6 was a predictor of serum HA.…”

“…Alterations in eGlx composition following an inflammatory insult is thought to be one of the earliest features of sepsis in humans ( Martin et al, 2016 , Steppan et al, 2011 ). Dogs with septic peritonitis have been shown to have increased hyaluronan concentrations on day 2 or 3 of hospitalisation compared to admission, these concentrations decreased during the recovery period ( Shaw et al, 2021 ). The same study identified relationships between serum interleukin (IL)− 6 and hyaluronan concentrations, suggesting an association between inflammation and eGlx degradation.…”

Evaluation of endothelial cell-specific molecule-1 as a biomarker of glycocalyx damage in canine myxomatous mitral valve disease

“…This allows more fluid to leak from compromised blood vessels, exacerbates interstitial edema, and triggers intravascular coagulation [ 6 – 8 ]. In previous studies, conditions such as septic peritonitis and parvoviral infections have been associated with eGCX damage in dogs [ 9 , 10 ]. Human studies have shown that conditions such as hypertension, hypercholesterolemia, cardiovascular disease, chronic kidney disease, diabetes, atherosclerosis, hypervolemia (aggressive fluid resuscitation), and ischemia–reperfusion injury can also lead to eGCX degradation [ 11 – 19 ].…”

Visualising the endothelial glycocalyx in dogs

“…The challenges of direct visualisation has led to the development of less invasive, indirect methods of eGlx evaluation ( Nieuwdorp et al, 2008 , Constantinescu et al, 2011 ) such as measurement of circulating eGlx components measured in humans including syndecans, hyaluronan and chondroitin sulphate ( Padberg et al, 2014 ). Their use has been reported in naturally occurring diseases in dogs ( Lawrence-Mills et al, 2022 , Shaw et al, 2021 ). Other indirect methods of eGlx measurement include sidestream dark field imaging ( Martens et al, 2013 ), where eGlx depth is inferred.…”