Fluids reverse the early lipopolysaccharide-induced albumin leakage in rodent mesenteric venules.
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.
Anning
Peter B
PB
Unit of Critical Care, National Heart and Lung Institute, Imperial College of Science Technology & Medicine, Dovehouse Street, SW3 6LY London, UK.
Finney
Simon J
SJ
Singh
Suveer
S
Winlove
C Peter
CP
Evans
Timothy W
TW
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
D000418:Albumins; D008070:Lipopolysaccharides