Clinical methods for assessment of endothelial glycocalyx integrity in cats : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Manawatū, New Zealand

Abstract

The endothelial glycocalyx (EG) is critical to vascular homeostasis, regulating permeability, blood flow, and inflammation. Despite its recognized importance in human medicine, clinical tools for EG assessment in veterinary patients remain underdeveloped. This PhD project aimed to explore, validate, and adapt methodologies for EG assessment in cats, with a focus on sidestream dark field videomicroscopy using the GlycoCheck™ system and the evaluation of EG shedding biomarkers.

The project began by establishing tolerance intervals for GlycoCheck™ parameters in a large cohort of healthy cats, confirming the feasibility of sublingual imaging for non-invasive EG thickness estimation. Species-specific features of the feline microvasculature, including variability in vessel counts and perfused vessel densities, were documented, providing essential baseline data.

Attempts to validate a commercial human syndecan-1 ELISA in cats revealed poor assay performance and uncertain specificity, highlighting the challenges of biomarker translation across species and the current lack of reliable EG shedding markers in veterinary medicine.

Two experimental studies investigated the effects of intravenous fluid administration on EG integrity in healthy cats. Neither a standard fluid challenge nor transient volume overload resulted in measurable EG thinning. However, anaesthetic effects and associations with haematological variables such as packed cell volume were identified, underscoring the importance of controlling for confounders. The findings also pointed to limitations of the GlycoCheck™ system, which estimates rather than directly measures EG thickness and may miss subtle microvascular changes.

A subsequent clinical study demonstrated the feasibility of applying GlycoCheck™ in hospitalized cats without disrupting workflow. However, no robust associations with clinical variables, including illness severity, were detected - likely due to small sample size and patient heterogeneity. Minor trends with fluid therapy and packed cell volume were noted but not confirmed.

Overall, this project identifies key methodological constraints in both imaging- and biomarker-based EG assessment. While promising, both approaches remain immature and require further refinement. By highlighting feasibility, limitations, and areas for future development, this work lays a foundation for advancing EG assessment in veterinary medicine and integrating microvascular evaluation into clinical research.