title: Myocardial dysfunction in early state of endotoxemia role of heme-oxygenase-1.
abstract: BACKGROUND
  The triggers and cellular mechanisms of cardiac dysfunction have not been clearly established during the early period following challenge with lipopolysaccharides (LPS) (<1 h post-LPS). The aim of the study was to evaluate the myocardial depression during early stage of endotoxemia, the relationship between oxidative stress production and cardiac dysfunction in a rat model of endotoxic shock, and its inhibition by heme-oxygenase-1 (HO-1) overexpression.
  
  
  METHODS
  LPS-induced myocardial deformation was assessed by tissue Doppler imaging and invasive hemodynamic measurements in rats 2 h after LPS challenge. Myocardial samples were processed for the measurements of tumor necrosis factor alpha (TNFalpha), nitric oxidase synthase II (NOSII), HO-1 gene expression, reactive oxygen species (ROS) production, and reduced glutathione/oxidized glutathione (GSH/GSSH) ratio.
  
  
  RESULTS
  Myocardial systolic and diastolic deformation was evident as determined by tissue Doppler imaging but left ventricular conventional echocardiographic parameters did not show significant alterations. Myocardial deformation was significantly associated with reactive oxygen species and TNFalpha overproduction. Pretreatment with hemin to induce HO-1 resulted in decreased oxidative stress and TNFalpha production, and prevented LPS-induced alterations in myocardium.
  
  
  CONCLUSIONS
  These preliminary results suggest myocardial alteration at a very early stage after LPS challenge associated with oxidative stress response. Manipulation of the HO-1 pathway may represent a future therapeutic strategy to counteract oxidative stress of endotoxemia and perhaps may limit future myocardial deformation.
authors.affiliation: Inserm (Institut National de la Santé et de la Recherche Médicale) Rouen University Medical School, Rouen, France. fabienne.tamion@chu-rouen.fr
authors.forename: Fabienne
authors.initials: F
authors.lastname: Tamion
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bauer
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.forename: Karine
authors.initials: K
authors.lastname: Laude
authors.forename: Sylvanie
authors.initials: S
authors.lastname: Renet
authors.forename: Michel
authors.initials: M
authors.lastname: Slama
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
mesh_terms: D000818:Animals; D004452:Echocardiography; D019446:Endotoxemia / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D006439:Hemodynamics; D008297:Male; D009206:Myocardium / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D016277:Ventricular Function, Left
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D006427:Hemin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat