Protection of the endothelial glycocalyx by antithrombin in an endotoxin-induced rat model of sepsis

• Published in: Thrombosis research 2018-11, Vol.171, p.1-6
• Main Authors: Iba, Toshiaki, Levy, Jerrold H., Hirota, Tatsuhiko, Hiki, Makoto, Sato, Koichi, Murakami, Taisuke, Nagaoka, Isao
• Format: Article
• Language: English
• Subjects: Animals; Antithrombin; Antithrombin Proteins - therapeutic use; Antithrombins - therapeutic use; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - immunology; Endothelium, Vascular - pathology; Endotoxins - immunology; Glycocalyx - drug effects; Glycocalyx - immunology; Glycocalyx - pathology; Hyaluronan; Hyaluronic Acid - blood; Hyaluronic Acid - immunology; Inflammation; Inflammation - blood; Inflammation - drug therapy; Inflammation - immunology; Inflammation - pathology; Microcirculation; Microcirculation - drug effects; Rats, Wistar; Sepsis; Sepsis - blood; Sepsis - drug therapy; Sepsis - immunology; Sepsis - pathology; Syndecan-1; Syndecan-1 - blood; Syndecan-1 - immunology
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2018.09.042

Injury and loss of the endothelial glycocalyx occur during the early phase of sepsis. We previously showed that antithrombin has a protective effect on this structure in vitro. Here, we investigated the possible protective effects of antithrombin in an animal model of sepsis. Wistar rats were injected with endotoxin, and circulating levels of syndecan-1, hyaluronan, albumin, lactate and other biomarkers were measured in an antithrombin-treated group and an untreated control group (n = 6 in each group). Intravital microscopy was used to observe leukocyte adhesion, microcirculation, and syndecan-1 staining. The circulating levels of syndecan-1 and hyaluronan were significantly reduced in the antithrombin-treated group, compared with the untreated controls. Lactate levels and albumin reduction were significantly attenuated in the antithrombin-treated group. Intravital microscopic observation revealed that both leukocyte adhesion and blood flow were better maintained in the treatment group. The syndecan-1 lining was disrupted after endotoxin treatment, and this derangement was attenuated by treatment with antithrombin. Antithrombin effectively maintained microcirculation and vascular integrity by protecting the glycocalyx in a rat sepsis model. [Display omitted]