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• W4385737699 abstract "Abstract Background Damage to the endothelial glycocalyx (eGC) and endothelial dysfunction have been reported to develop during cardiac ischemia-and-reperfusion injury (IRI), such as ST-elevation myocardial infarction (STEMI). For patients with acute ischemic syndromes and cardiogenic shock a door-to-balloon time (D2B) < 60 min with rapid revascularization was shown to reduce both mortality and nonfatal complications. Here, we hypothesize that prolonged D2B is associated with an unfavorable outcome for the eGC of patients with STEMI. Methods Data of 126 individuals were analyzed in this study. Sixty-three STEMI patients with cardiogenic shock in the event of STEMI were included. All received revascularization through primary percutaneous coronary intervention (PCI). 63 age- and sex-matched healthy volunteers served as controls. After stimulating endothelial cells with patient sera, the nanomechanical properties of the eGC were analyzed using the atomic force microscopy-based nanoindentation technique. Serum levels of eGC components as well as complement anaphylatoxins and angiopoetin-2 were measured via ELISA. Nitric oxide (NO) levels were determined chemiluminescence-based. Results eGC height and stiffness (both, p < 0.001) as well as NO concentration (p < 0.001) were reduced after STEMI. Longer D2B led to significantly higher amounts of eGC components (syndecan-1: 35.5 vs. 136.7 ng/ml; p < 0.001 / heparan sulfate: 4.6 vs. 10.8 ng/ml; p < 0.001 / hyaluronic acid: 116.7 vs. 182.9 µg/ml; p < 0.0001) and troponin-t (p < 0.01) in the patient sera. Notably, D2B had a strong impact on patient outcome. D2B > 60 min led to pronounced loss of eGC height and stiffness (both, p < 0.001), activated the complement system (p < 0.001), and prolonged the hospital stay (p < 0.01) compared to D2B ≤ 60 min. Conclusion Increased D2B led to severe eGC shedding and endothelial dysfunction in a temporal context. In addition, levels of syndecan-1 and proinflammatory mediators correlated with prolonged D2B, indicating a time-dependent immune reaction during cardiogenic shock with increased IRI to the eGC and prolonged hospitalization. D2B therefore appears to be a crucial factor for endothelial IRI in the case of STEMI with cardiogenic shock. Combining the clinical evaluation of the eGC condition with levels of biomarkers such as syndecan-1 might serve as important predictor for eGC impairment of STEMI patients with cardiogenic shock in the future." @default.
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• W4385737699 date "2023-08-10" @default.
• W4385737699 modified "2023-09-27" @default.
• W4385737699 title "Prolonged Door-to-Balloon time leads to glycocalyx damage and endothelial dysfunction in patients with ST-Elevation Myocardial Infarction and cardiogenic shock" @default.
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• W4385737699 doi "https://doi.org/10.21203/rs.3.rs-3234193/v1" @default.
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