title: Detrimental hemodynamic and inflammatory effects of microparticles originating from septic rats.
abstract: OBJECTIVE
  Microparticles (MPs) are membrane vesicles with procoagulant and proinflammatory properties released during cell activation and might be potentially involved in the pathophysiology of septic shock. This study was designed to assess the effects of MPs from septic origin on the systemic hemodynamics as well as on the inflammatory, oxidative, and nitrosative stresses.
  
  
  METHODS
  A prospective, randomized, controlled experimental study with repeated measurements.
  
  
  METHODS
  Investigational animal laboratory.
  
  
  METHODS
  Forty healthy rats were randomly allocated to three groups: 10 animals inoculated with MPs isolated from control rats (cMPs), 15 animals inoculated with MPs isolated from sham rats (shMPs), and 15 animals inoculated with MPs isolated from rats with peritonitis (sMPs).
  
  
  METHODS
  Rats were anesthetized, mechanically ventilated, and infused with the same amount of cMPs, shMPs, or sMPs. We measured the heart rate, mean arterial pressure, carotid artery, and portal vein blood flows. Hemodynamic parameters were recorded during 7 hours, and then animals were killed. Aorta and heart were harvested for further in vitro tissue analyses.
  
  
  RESULTS
  1) The cellular origin (phenotype) but not the circulating concentration of MPs was different in septic rats, characterized by a significant increase in leukocyte-derived MPs. 2) sMPs but not cMPs or shMPs decreased mean arterial pressure without any effect on carotid artery and portal vein blood flows. 3) Rats inoculated with sMPs exhibited an increase in superoxide ion production and nuclear factor kappa B activity, overexpression of inducible nitric oxide synthase with subsequent nitric oxide overproduction and decrease in endothelial nitric oxide synthase activation.
  
  
  CONCLUSIONS
  Rats with sepsis induced by peritonitis exhibited a specific phenotype of MPs. Inoculation of sMPs in healthy rats reproduced hemodynamic, septic inflammatory patterns, associated with oxidative and nitrosative stresses.
authors.affiliation: Laboratoire HIFIH UPRES EA 3859 , Université d'Angers, Angers, France.
authors.forename: Satar
authors.initials: S
authors.lastname: Mortaza
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Martinez
authors.forename: Céline
authors.initials: C
authors.lastname: Baron-Menguy
authors.forename: Mélanie
authors.initials: M
authors.lastname: Burban
authors.forename: Mathilde
authors.initials: M
authors.lastname: de la Bourdonnaye
authors.forename: Lionel
authors.initials: L
authors.lastname: Fizanne
authors.forename: Marc
authors.initials: M
authors.lastname: Pierrot
authors.forename: Paul
authors.initials: P
authors.lastname: Calès
authors.forename: Daniel
authors.initials: D
authors.lastname: Henrion
authors.forename: Ramaroson
authors.initials: R
authors.lastname: Andriantsitohaina
authors.forename: Alain
authors.initials: A
authors.lastname: Mercat
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.forename: Ferhat
authors.initials: F
authors.lastname: Meziani
mesh_terms: D000818:Animals; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000502:physiology*; D006439:Hemodynamics; D007249:Inflammation / Q000209:etiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*