title: Early adverse changes in liver microvascular circulation during experimental septic shock are not linked to an absolute nitric oxide deficit.
abstract: Nitric oxide (NO) is believed to play a key role in adverse microvascular changes during sepsis. A deficit in NO has been evoked as a potential mechanism of microcirculatory deterioration in the early phase of septic shock. The aim of this study was to evaluate simultaneously and continuously both hepatic microcirculation and local NO production during early experimental sepsis. Wistar male rats were divided into two groups: a sepsis group undergoing cecal ligation and puncture (CLP) peritonitis and a control group undergoing sham surgery. Hepatic microcirculation was continuously monitored using a laser Doppler probe and local nitric oxide (NO) production by means of a specific electrode. Constitutive and inducible NO synthase production was assessed 2h after surgery, at onset of shock, and at 2 and 3h after shock. In control animals, hepatic microcirculatory perfusion and NO production remained stable throughout the experiment. In septic animals, whereas a fall in microcirculatory perfusion was noted as early as 2h after CLP, NO concentration remained stable and further increased after the onset of shock. At this time, inducible NO synthase was the only isoform significantly elevated. In this non-resuscitated experimental model of sepsis, an absolute liver deficit of NO could not explain the early adverse changes in the local microvascular system.
authors.affiliation: Département d'anesthésie réanimation, Centre hospitalier universitaire de Saint-Etienne, 42055 Saint-Etienne Cedex 02, France; Unité de recherche EA 4174, Hémostase, Inflammation et Sepsis, UCB Lyon 1, 69008 Lyon, France. Electronic address: jerome.morel@chu-st-etienne.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Morel
authors.forename: Jacques Yuan
authors.initials: JY
authors.lastname: Li
authors.forename: Pierre
authors.initials: P
authors.lastname: Eyenga
authors.forename: Anne
authors.initials: A
authors.lastname: Meiller
authors.forename: Marie Paule
authors.initials: MP
authors.lastname: Gustin
authors.forename: Giampiero
authors.initials: G
authors.lastname: Bricca
authors.forename: Serge
authors.initials: S
authors.lastname: Molliex
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Viale
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D002432:Cecum / Q000382:microbiology / Q000601:surgery; D004195:Disease Models, Animal; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D008099:Liver / Q000098:blood supply* / Q000378:metabolism*; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D009569:Nitric Oxide / Q000172:deficiency*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011677:Punctures; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: CLP; NO; NOS; RT-PCR; cecal ligation and puncture; mRNA; messenger RNA; nitric oxide; nitric oxide synthase; real-time polymerase chain reaction