# Protective Treatments against Endothelial Glycos
## 4 Discussion  
To the authors' knowledge, there has been no systematic review to investigate treatments to protect against EG degradation in surgery. In our study, the greatest change in plasma syndecan-1 concentrations from baseline values, was generally found at the first timepoint measured post-operatively. Syndecan-1 is a marker for greater trauma of EG shedding, so more time may be required for this extent of damage to occur and to be detected. The transient increase can be explained by the proteolytic degradation of the glycocalyx with subsequent rapid clearance, especially via the kidneys [30]. A slow systemic degradation could be explained by a general activation of leucocytes and platelets with an associated release of enzymes that shed the glycocalyx [31]  
Pooled data from 196 patients in 5 randomised controlled trials for protective treatments against EG degradation in surgery indicated that patients treated with experimental drugs were more likely to respond than those treated with placebo, with a pooled mean difference of \(-8.94\) (95% CI: \(-19.60\), \(1.61\)). Randomised controlled trials using methylprednisolone were shown to have the greatest effect to inhibit elevation of syndecan-1 levels. This may be important as it provides evidence for the development of personalised interventions, targeting patients in selected groups with altered risk profiles, for example, using bolus I.V. methylprednisolone in patients with high baseline values of endothelial activation and damage. [PERSON] study [24] found that the effect of methylprednisolone on syndecan-1, sTM and VEGF concentrations was dependant on the time of sampling, with these outcomes increasing with time. [PERSON] study [27] showed similar changes in which methylprednisolone failed to inhibit the increase of syndecan-1 shedding at the early time-points, yet showed significant lowering of syndecan-1 levels to its corresponding control group for later time-points. A combination of the previous work on interleukins by [PERSON] [32] and these present syndecan-1 results suggest that methylprednisolone probably mediates the conservation of glycocalyx by an anti-inflammatory action. This is operative at the time-points when interleukin production is regulated via de novo protein synthesis due to glucocorticoid receptor activation. Of the three randomised clinical trials, with only one of them to have their upper-confidence interval to go beyond the line of no effect by 0.79 ng/mL, future work on methylprednisolone could be promising to protect the EG in surgery. [PERSON] [22] showed hydrocortisone to reduce minor disturbances and not significant degradation of the EG. This shows that mechanistic pathways involved with shedding of heparan sulphate side-chains evoked by the combined stimuli of surgery were more susceptible to inhibition by hydrocortisone than the one leading to cleavage of the transmembrane core protein, syndecan-1. Whilst inflammatory markers (IL-6 and CRP) had shown significantly higher levels in the control group to the hydrocortisone group post-operatively, it had no relevant influence on inflammatory clinical parameters. As highlighted previously, the [PERSON] study [24] showed the effect of methylprednisolone on syndecan-1, sTM and VEGF concentrations was dependant on the time of sampling, with these outcomes increasing with time. However, this study showed no correlation with changes in CRP and any of the EG degradation markers. Analysis of the Nemme study [26] was challenging with no control group, however, there were no marked changes in BNP, syndecan-1, heparan sulphate and CRP between the two groups. There was no correlation between inflammatory markers (BNP and CRP) and glycocalyx shedding products. The following results from the three articles differed from their previous research. Experimental studies had shown hydrocortisone to provide EG protective properties, most probably due to the stabilisation of mast cells, and, therefore, the amelioration of histamine, cytokines, lysosomes and protease production [9; 33; 34].