Toshiaki Iba1, Jerrold H Levy2, Tatsuhiko Hirota3, Makoto Hiki4, Koichi Sato5, Taisuke Murakami6, Isao Nagaoka7. 1. Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: toshiiba@cf6.so-net.ne.jp. 2. Department of Anesthesiology and Critical Care, Duke University School of Medicine, United States of America. Electronic address: jerrold.levy@duke.edu. 3. Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: tatsuhiko.hirota@asahigroup-holdings.com. 4. Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: m-hiki@juntendo.ac.jp. 5. Department of Surgery, Juntendo Shizuoka Hospital, Juntendo University Graduate School of Medicine, Japan. Electronic address: kou-sato@chive.ocn.ne.jp. 6. Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Japan. Electronic address: t-mura@juntendo.ac.jp. 7. Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Japan. Electronic address: nagaokai@juntendo.ac.jp.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Antithrombin effectively maintained microcirculation and vascular integrity by protecting the glycocalyx in a rat sepsis model.
INTRODUCTION: 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. METHODS: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. RESULTS: 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. CONCLUSION: Antithrombin effectively maintained microcirculation and vascular integrity by protecting the glycocalyx in a ratsepsis model.
Authors: Michael Hultström; Karin Fromell; Anders Larsson; Barbro Persson; Bo Nilsson; Susan E Quaggin; Christer Betsholtz; Robert Frithiof; Miklos Lipcsey; Marie Jeansson Journal: Biomedicines Date: 2022-06-06
Authors: Mohamed ElSaadani; Syed M Ahmed; Christina Jacovides; Alfonso Lopez; Victoria E Johnson; Lewis J Kaplan; C William Schwab; Douglas H Smith; Jose L Pascual Journal: J Trauma Acute Care Surg Date: 2021-02-01 Impact factor: 3.313