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Multimodal measurement of glycocalyx degradation during coronary artery bypass grafting
Martine E Bol1,2, J B Huckriede3, K G H van de Pas1
1Department of Intensive Care Medicine, Maastricht University Medical Center (MUMC+), Maastricht, Netherlands.
Insights
Glycocalyx thinning and endothelial dysfunction increase during coronary artery bypass grafting (CABG) surgery. No single marker accurately reflects the complex changes in glycocalyx properties during this procedure.
Area of Science:
- Cardiovascular Surgery
- Endothelial Biology
- Biomarker Research
Background:
- Glycocalyx shedding and endothelial dysfunction are implicated in critical illness and major surgeries like CABG.
- Current methods for measuring human glycocalyx properties lack a gold standard.
- CABG surgery is a known trigger for glycocalyx shedding.
Purpose of the Study:
- To compare various indices of glycocalyx shedding and dysfunction.
- To assess changes in glycocalyx markers during elective CABG surgery.
- To evaluate correlations between different glycocalyx measurements.
Main Methods:
- Sublingual glycocalyx thickness was assessed using the perfused boundary region (PBR) via sidestream dark field imaging.
- Plasma levels of glycocalyx shedding products (syndecan-1, hyaluronan, heparan sulfate) were measured.
- Plasma markers of endothelial activation and glycocalyx function (Ang-2, Tie-2, E-selectin, thrombomodulin) were quantified.
Main Results:
- The PBR increased significantly after cardiopulmonary bypass (CPB) initiation, indicating glycocalyx thinning.
- Levels of shedding markers (syndecan-1, hyaluronan, heparan sulfate) and functional markers (Ang-2, Tie-2, thrombomodulin) also increased.
- E-selectin levels rose throughout the CPB procedure.
- Correlations between different markers were moderate to weak, suggesting marker complexity.
Conclusions:
- Glycocalyx thinning and impaired function, alongside increased endothelial activation, occur during CABG with CPB.
- The complex nature of glycocalyx changes prevents identification of a single representative marker.
- Further research is needed to establish reliable methods for assessing glycocalyx integrity.
Background:
Glycocalyx shedding and subsequent endothelial dysfunction occur in many conditions, such as in sepsis, in critical illness, and during major surgery such as in coronary artery bypass grafting (CABG) where it has been shown to associate with organ dysfunction. Hitherto, there is no consensus about the golden standard in measuring glycocalyx properties in humans. The objective of this study was to compare different indices of glycocalyx shedding and dysfunction. To this end, we studied patients undergoing elective CABG surgery, which is a known cause of glycocalyx shedding.
Materials And Methods:
Sublingual glycocalyx thickness was measured in 23 patients by: 1) determining the perfused boundary region (PBR)-an inverse measure of glycocalyx thickness-by means of sidestream dark field imaging technique. This is stated double, 2) measuring plasma levels of the glycocalyx shedding products syndecan-1, hyaluronan, and heparan sulfate and 3) measuring plasma markers of impaired glycocalyx function and endothelial activation (Ang-2, Tie-2, E-selectin, and thrombomodulin). Measurements were performed directly after induction, directly after onset of cardiopulmonary bypass (CPB), and directly after cessation of CPB. We assessed changes over time as well as correlations between the various markers.
Results:
The PBR increased from 1.81 ± 0.21 μm after induction of anesthesia to 2.27 ± 0.25 μm (p < 0.0001) directly after CPB was initiated and did not change further during CPB. A similar pattern was seen for syndecan-1, hyaluronan, heparan sulfate, Ang-2, Tie-2, and thrombomodulin. E-selectin levels also increased between induction and the start of CPB and increased further during CPB. The PBR correlated moderately with heparan sulfate, E-selectin, and thrombomodulin and weakly with Syndecan-1, hyaluronan, and Tie-2. Shedding markers syndecan-1 and hyaluronan correlated with all functional markers. Shedding marker heparan sulfate only correlated with Tie-2, thrombomodulin, and E-selectin. Thrombomodulin correlated with all shedding markers.
Conclusion:
Our results show that glycocalyx thinning, illustrated by increased sublingual PBR and increased levels of shedding markers, is paralleled with impaired glycocalyx function and increased endothelial activation in CABG surgery with CPB. As correlations between different markers were limited, no single marker could be identified to represent the glycocalyx in its full complexity.
