Prolonged Cardiopulmonary Bypass is Associated With Endothelial Glycocalyx Degradation

The endothelial glycocalyx (EG) is a critical structure that supports vascular integrity and regulates permeability. Prior research has shown that EG damage can lead to increased vascular permeability and immune activation. However, the relationship between surgical interventions and EG degradation remains unclear. No prior work had resolved how prolonged surgical procedures might affect EG integrity. The role of syndecan-1 as a soluble marker of EG shedding is well established. Yet, the connection between syndecan-1 levels and surgical duration had not been fully explored. Current evidence suggests that EG damage may contribute to postoperative inflammation. However, the precise mechanisms linking surgical time to EG degradation remain uncertain. This gap motivated an investigation into whether prolonged cardiopulmonary bypass (CPB) could trigger EG breakdown. The study aimed to clarify if syndecan-1 levels could serve as a reliable indicator of EG damage during extended CPB.

The study aimed to explore whether prolonged cardiopulmonary bypass (CPB) is associated with endothelial glycocalyx (EG) degradation. Specifically, the researchers sought to determine if increased CPB duration correlates with elevated levels of soluble syndecan-1, a known marker of EG shedding. They also investigated how EG damage might influence inflammatory responses during surgery. The study focused on measuring syndecan-1 levels in relation to CPB duration and assessing their impact on white blood cell populations. Additionally, the researchers tested whether syndecan-1 could directly affect neutrophil mobilization. The goal was to establish a potential link between EG degradation and postoperative inflammation. This work aimed to provide a clearer understanding of how surgical time affects vascular integrity. The findings could inform new therapeutic strategies for patients undergoing extended CPB procedures.

The researchers collected blood samples from 54 patients undergoing cardiac surgery with CPB at multiple time points. These samples were analyzed for soluble syndecan-1 levels, mitochondrial DNA (mtDNA), and white blood cell subpopulations. Flow cytometry was used to assess changes in leukocyte profiles. Plasma levels of mtDNA were measured using quantitative polymerase chain reaction. Syndecan-1 concentrations were quantified to evaluate EG degradation. To investigate the role of syndecan-1 in neutrophil mobilization, mice were administered recombinant syndecan-1 intravenously. Neutrophil counts in circulation and bone marrow were then measured. Correlation analysis was performed to assess the relationship between CPB duration and syndecan-1 levels. The study design allowed for a direct evaluation of EG damage and its inflammatory consequences.

The study found that prolonged CPB is associated with increased plasma levels of soluble syndecan-1, a marker of EG degradation. Syndecan-1 levels peaked at 4-8 hours post-CPB and remained elevated at 24 hours. A strong positive correlation was observed between CPB duration and syndecan-1 concentration (r_s = 0.488, P < 0.001). Neutrophil counts also increased significantly at 4-8 hours and 24 hours after surgery. A moderate correlation was found between syndecan-1 levels and neutrophil count (r_s = 0.351, P = 0.038). In mice, intravenous administration of recombinant syndecan-1 led to a 2.5-fold increase in circulating neutrophils. Bone marrow neutrophil counts decreased correspondingly, suggesting a mobilization effect. These findings indicate that EG degradation during CPB may trigger neutrophil release from the bone marrow.

The authors suggest that prolonged CPB is associated with endothelial glycocalyx (EG) degradation, as indicated by elevated soluble syndecan-1 levels. This EG damage appears to correlate with increased neutrophil mobilization from the bone marrow. The study proposes that syndecan-1 may act as a signaling molecule that promotes neutrophil egress. These findings support the idea that EG shedding during CPB could contribute to postoperative inflammation. The researchers propose that therapies targeting EG preservation may benefit patients undergoing extended CPB. However, they caution that further studies are needed to confirm the causal relationship between EG degradation and neutrophil activation. The results do not establish EG degradation as the sole driver of postoperative inflammation but suggest it as a contributing factor. The authors emphasize the need for future research to explore EG-targeted interventions in surgical settings.