title: Fluids reverse the early lipopolysaccharide-induced albumin leakage in rodent mesenteric venules.
abstract: OBJECTIVE
  Volume resuscitation is clinically beneficial in patients with sepsis, but few data exist concerning the effects of fluid administration on early events in the inflammatory process. Vascular permeability, leukocyte rolling and leukocyte adhesion in the rodent mesenteric microcirculation were assessed in vivo using intravital microscopy, and the effect of fluid administration on lipopolysaccharide (LPS)-induced changes recorded.
  
  
  METHODS
  Prospective, repeated measures study.
  
  
  METHODS
  University hospital laboratory.
  
  
  METHODS
  Male Wistar rats in six groups.
  
  
  METHODS
  All animals underwent intravital microscopic examination of mesenteric post-capillary venules. LPS or vehicle was applied topically. Animals received either no additional fluids, 0.9% saline (16 ml/kg per h) or 5% human albumin (16 ml/kg per h) commencing 30 min prior to LPS/vehicle administration.
  
  
  RESULTS
  Leukocyte rolling, firm adhesion and blood velocity were observed directly. Vascular permeability was assessed using the flux of fluorescently labelled albumin into the interstitium. LPS significantly increased the median (IQR) number of leukocytes rolling and firmly adherent relative to baseline (at 60 min rolling increased from 12.0 (10.3-13.8) to 40.3 (36.0-47.5) cells/min; adhesion increased from 1 (1-2) to 17 (12-26) cells/100 microm; n=5, p<0.01). Transvascular albumin flux was significantly increased 45 min after LPS application (p<0.01), but not after vehicle. Administration of either 0.9% saline (n=5) or 5% human albumin (n=6), significantly attenuated LPS-induced increases in albumin flux (p<0.05), leukocyte rolling (p<0.01) and adhesion (p<0.01). Fluid administration did not appear to alter shear rates.
  
  
  CONCLUSIONS
  Pre-emptive volume administration with either saline or albumin prevented early LPS-induced microcirculatory changes by an undefined effect that is unrelated to changes in microvascular flow.
authors.affiliation: Unit of Critical Care, National Heart and Lung Institute, Imperial College of Science Technology & Medicine, Dovehouse Street, SW3 6LY London, UK.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Anning
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Finney
authors.forename: Suveer
authors.initials: S
authors.lastname: Singh
authors.forename: C Peter
authors.initials: CP
authors.lastname: Winlove
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Evans
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D005440:Fluid Therapy; D007249:Inflammation / Q000139:chemically induced* / Q000628:therapy; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects*; D023421:Models, Animal; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000418:Albumins; D008070:Lipopolysaccharides