title: The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats.
abstract: OBJECTIVE
  To study the role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats.
  
  
  METHODS
  Rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 6), a group in which LPS administration was followed by immediate fluid resuscitation which prevented the drop of renal blood flow (EARLY group) (n = 6), and a group in which LPS administration was followed by delayed (i.e., a 2-h delay) fluid resuscitation (LATE group) (n = 6). Renal blood flow was measured using a transit-time ultrasound flow probe. Microvascular perfusion and oxygenation distributions in the renal cortex were assessed using laser speckle imaging and phosphorimetry, respectively. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were measured as markers of systemic inflammation. Furthermore, renal tissue samples were stained for leukocyte infiltration and inducible nitric oxide synthase (iNOS) expression in the kidney.
  
  
  RESULTS
  LPS infusion worsened both microvascular perfusion and oxygenation distributions. Fluid resuscitation improved perfusion histograms but not oxygenation histograms. Improvement of microvascular perfusion was more pronounced in the EARLY group compared with the LATE group. Serum cytokine levels decreased in the resuscitated groups, with no difference between the EARLY and LATE groups. However, iNOS expression and leukocyte infiltration in glomeruli were lower in the EARLY group compared with the LATE group.
  
  
  CONCLUSIONS
  In our model, prevention of endotoxemia-induced systemic hypotension by immediate fluid resuscitation (EARLY group) did not prevent systemic inflammatory activation (IL-6, IL-10, TNF-α) but did reduce renal inflammation (iNOS expression and glomerular leukocyte infiltration). However, it could not prevent reduced renal microvascular oxygenation.
authors.affiliation: Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. matthieu.m.legrand@gmail.com
authors.forename: Matthieu
authors.initials: M
authors.lastname: Legrand
authors.forename: Rick
authors.initials: R
authors.lastname: Bezemer
authors.forename: Asli
authors.initials: A
authors.lastname: Kandil
authors.forename: Cihan
authors.initials: C
authors.lastname: Demirci
authors.forename: Didier
authors.initials: D
authors.lastname: Payen
authors.forename: Can
authors.initials: C
authors.lastname: Ince
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism / Q000503:physiopathology*; D005440:Fluid Therapy; D007249:Inflammation; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000382:microbiology; D008070:Lipopolysaccharides; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D010100:Oxygen / Q000032:analysis; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000502:physiology*; D018805:Sepsis
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D010100:Oxygen