Prolonged Door-to-Balloon Time Leads to Endothelial Glycocalyx Damage and Endothelial Dysfunction in Patients with
Carl Vahldieck1,2, Benedikt Fels2,3, Samuel Löning2
1Department of Anesthesiology and Intensive Care Medicine, University Medical Centre Schleswig-Holstein Campus Luebeck, 23538 Luebeck, Germany.
Insights
Prolonged door-to-balloon time in ST-elevation myocardial infarction (STEMI) significantly damages the endothelial glycocalyx (eGC). This damage impairs endothelial function and increases hospital stay, highlighting D2B as critical for eGC integrity in STEMI patients.
Area of Science:
- Cardiovascular Medicine
- Endothelial Biology
- Ischemic Heart Disease Research
Background:
- Endothelial glycocalyx (eGC) damage is observed in acute ischemic events like ST-elevation myocardial infarction (STEMI).
- Shorter door-to-balloon (D2B) times (<60 min) in STEMI are linked to reduced mortality and complications.
Purpose of the Study:
- To investigate the association between endothelial glycocalyx (eGC) condition, door-to-balloon (D2B) duration, and endothelial function in STEMI patients.
- To determine if D2B time impacts eGC integrity and markers of endothelial dysfunction.
Main Methods:
- Analyzed nanomechanical properties (height, stiffness) of eGC using atomic force microscopy-based nanoindentation.
- Quantified eGC components (syndecan-1, heparan sulfate, hyaluronic acid) via ELISA.
- Measured nitric oxide (NO) levels using chemiluminescence in 126 STEMI patients and healthy controls.
Main Results:
- STEMI patients exhibited reduced eGC height/stiffness and NO levels compared to controls (p < 0.001).
- D2B time > 60 min correlated with significantly higher serum eGC components (p < 0.001).
- Longer D2B (>60 min) resulted in decreased eGC height/stiffness, reduced NO, complement activation, and prolonged hospitalization (p < 0.01).
Conclusions:
- Prolonged D2B in STEMI leads to significant eGC shedding and endothelial dysfunction.
- eGC components and inflammatory mediators correlate with longer D2B, indicating a time-dependent inflammatory response.
- D2B duration is a critical factor in eGC damage, suggesting eGC evaluation could predict endothelial function in STEMI.
Abstract:
Damage to the endothelial glycocalyx (eGC) has been reported during acute ischemic events like ST-elevation myocardial infarction (STEMI). In STEMI, a door-to-balloon time (D2B) of <60 min was shown to reduce mortality and nonfatal complications. Here, we hypothesize that eGC condition is associated with D2B duration and endothelial function during STEMI. One hundred and twenty-six individuals were analyzed in this study (STEMI patients vs. age-/sex-matched healthy volunteers). After stimulating endothelial cells with patient/control sera, the eGC's nanomechanical properties (i.e., height/stiffness) were analyzed using the atomic force microscopy-based nanoindentation technique. eGC components were determined via ELISA, and measurements of nitric oxide levels (NO) were based on chemiluminescence. eGC height/stiffness (both p < 0.001), as well as NO concentration (p < 0.001), were reduced during STEMI. Notably, the D2B had a strong impact on the endothelial condition: a D2B > 60 min led to significantly higher serum concentrations of eGC components (syndecan-1: p < 0.001/heparan sulfate: p < 0.001/hyaluronic acid: p < 0.0001). A D2B > 60 min led to the pronounced loss of eGC height/stiffness (both, p < 0.001) with reduced NO concentrations (p < 0.01), activated the complement system (p < 0.001), and prolonged the hospital stay (p < 0.01). An increased D2B led to severe eGC shedding, with endothelial dysfunction in a temporal context. eGC components and pro-inflammatory mediators correlated with a prolonged D2B, indicating a time-dependent immune reaction during STEMI, with a decreased NO concentration. Thus, D2B is a crucial factor for eGC damage during STEMI. Clinical evaluation of the eGC condition might serve as an important predictor for the endothelial function of STEMI patients in the future.
