The effect of tetrastarch on the endothelial glycocalyx layer in early hemorrhagic shock using fluorescence intravital microscopy: a mouse model

Background: This study aimed to clarify the effects of the optimal timing of infusion therapy during massive hemorrhage by measuring the glycocalyx (GCX) damage and its effect on vascular endothelial cell dysfunction. Methods: : In this randomized control animal study, we withdrew 1.5 mL of blood and administered 1.5 mL of infusion resuscitation. The mice were divided into the following six groups according to the type of infusion and administration timing: group NS-NS (Normal Saline (NS)→NS), group NS-Hydroxyethyl starch (HES) (NS→ Hydroxyethyl starch 130/0.4/9 (HES130)), group HES-NS (HES130→NS), group NS-Albumin (ALB) (NS→albumin), group ALB-NS (albumin→NS), and group C (control, no withdrawal or infusion). We investigated the vascular endothelial dysfunction based on the GCX impairment, measured indirectly through the interstitial fluorescence intensity and syndecan-1 concentration. Results: : The GCX index (GCXI) of a 40 μm artery was significantly larger in group C than in the other groups (P<0.01). Similarly, the GCXI for a 60 μm artery was significantly larger compared with the NS-NS (P≤0.05), NS-HES (P≤0.01), and NS-ALB groups (P≤0.05). The plasma syndecan-1 concentration, at 7.70±5.71 ng/mL, was significantly lower in group C than in group NS-NS (P≤0.01). The tetramethylrhodamine-labeled dextran (TMR-DEX40) fluorescence intensity in the ALB-NS and HES-NS groups, as well as the fluorescein isothiocyanate-labeled hydroxyethyl starch (FITC-HES130) fluorescence intensity in the NS-HES and HES-NS groups, were not significantly different from those of group C at any time point. FITC-HES130 was localized on the inner wall of the vessels in groups without HES130 infusion but uniformly distributed in groups treated with HES130. Conclusions: : In an acute massive hemorrhage mouse model, initial fluid resuscitation therapy with saline administration impaired GCX and increased the vascular permeability. Prior administration of HES130 prevented the progression of GCX damage. Early colloid resuscitation may improve endothelial cell function.