title: Endothelial glycocalyx damage during endotoxemia coincides with microcirculatory dysfunction and vascular oxidative stress.
abstract: The glycocalyx constitutes the first line of the blood tissue interface and is thus involved in many physiological processes, deregulation of which may lead to microvascular dysfunction. Because administration of LPS is accompanied by severe microvascular dysfunction, the purpose of the study was to investigate microvascular glycocalyx function during endotoxemia. Bolus infusion of LPS (10 mg kg(-1)) to male Sprague-Dawley rats elicited the development of hyporeactivity to vasoactive agents and microvascular derangements, including decreased capillary density and significant increases in intermittent and stopped flow capillaries in the small intestine muscularis layer compared with controls. LPS elicited plasma hyluronan release and reduction in endothelial surface thickness, indicative of glycocalyx degradation. Because endothelial glycocalyx is extremely sensitive to free radicals, oxidative stress was evaluated by oxidation of dihydrorhodamine in microvascular beds and levels of heart malondialdehyde and plasma carbonyl proteins, which were all increased in LPS-treated rats. Activated protein C (240 microg kg(-1) h(-1)) enhanced systemic arterial pressure response to norepinephrine in LPS-treated rats. Activated protein C (240 microg kg(-1) h(-1)) prevented capillary perfusion deficit in the septic microvasculature that were associated with reduced oxidative stress and preservation of glycocalyx. Our findings support the conclusion that LPS induces major microcirculation dysfunction accompanied by microvascular oxidative stress and glycocalyx degradation that may be limited by activated protein C treatment.
authors.affiliation: EA 2689, IMPRT-IFR114, Université de Lille 2, Département de Physiologie, Faculté de Médecine, and Laboratoire de Biochimie-Biologie Moléculaire, CHRU Lille, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Marechal
authors.forename: Raphael
authors.initials: R
authors.lastname: Favory
authors.forename: Olivier
authors.initials: O
authors.lastname: Joulin
authors.forename: David
authors.initials: D
authors.lastname: Montaigne
authors.forename: Sidi
authors.initials: S
authors.lastname: Hassoun
authors.forename: Brigitte
authors.initials: B
authors.lastname: Decoster
authors.forename: Farid
authors.initials: F
authors.lastname: Zerimech
authors.forename: Remi
authors.initials: R
authors.lastname: Neviere
mesh_terms: D000818:Animals; D002244:Carbon / Q000737:chemistry; D004730:Endothelium, Vascular / Q000166:cytology; D019446:Endotoxemia / Q000378:metabolism*; D005609:Free Radicals; D005786:Gene Expression Regulation; D019276:Glycocalyx / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008833:Microcirculation; D018384:Oxidative Stress; D011486:Protein C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005609:Free Radicals; D008070:Lipopolysaccharides; D011486:Protein C; D008315:Malondialdehyde; D002244:Carbon