title: Physostigmine reverses disturbances of the intestinal microcirculation during experimental endotoxemia.
abstract: Intestinal microcirculatory disturbances play an important role in the pathophysiology of sepsis. A neural anti-inflammatory pathway has been suggested as a potential target for therapy that may dampen systemic inflammation. The aim of this study is to investigate the effects of physostigmine, a cholinesterase inhibitor, on the intestinal microcirculation and vascular contractility in experimental endotoxemia. Endotoxemia was induced in Lewis rats by intravenous lipopolysaccharide (LPS) administration. Animals were treated with either physostigmine or saline (control) following LPS challenge. The intestinal microcirculation, including leukocyte-endothelial interaction, functional capillary density (FCD) and non-perfused capillary density (NCD), was examined by intravital microscopy (IVM) 2 hours after LPS administration. The impact of physostigmine on vascular contractility of rat aortic rings was examined by in vitro myography. Physostigmine significantly reduced the number of adhering leukocytes in intestinal submucosal venules (V1 venules: -61%, V3 venules: -36%) of LPS animals. FCD was significantly increased by physostigmine treatment (circular muscle layer: +180%, longitudinal muscle layer: +162%, mucosa: +149%). Low concentrations of physostigmine produced significant contraction of aortic ring preparations, whereas high concentrations produced relaxation. In conclusion, physostigmine treatment significantly improved the intestinal microcirculation in experimental endotoxemia by reducing leukocyte adhesion and increasing FCD.
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
authors.forename: Dragan
authors.initials: D
authors.lastname: Pavlovic
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Rüb
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Masur
authors.affiliation: Faculty of Medicine, Department of Orthodontics, University of Greifswald, Greifswald, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Spassov
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: Whynot
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.
authors.forename: Orlando
authors.initials: O
authors.lastname: Hung
authors.affiliation: Department of Anaesthesiology and Intensive Care, DRK Kliniken Berlin, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kern
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada Faculty of Medicine Hradec Kralove, Department of Anesthesiology and Intensive Care Medicine, Charles University Prague, Czech Republic.
authors.forename: Islam
authors.initials: I
authors.lastname: Saleh Abdo
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.
authors.forename: Romesh
authors.initials: R
authors.lastname: Shukla
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada Faculty of Medicine Hradec Kralove, Department of Anesthesiology and Intensive Care Medicine, Charles University Prague, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Cerny
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada Department of Anesthesia and Intensive Care Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D010830:Physostigmine / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D018805:Sepsis
chemical_list: D002800:Cholinesterase Inhibitors; D010830:Physostigmine
keywords: Physostigmine; endotoxemia; intravital microscopy; microcirculation; sepsis