Early physiological and biological features in three animal models of induced acute lung injury

Intensive Care Med. 2010 Feb;36(2):347-55. doi: 10.1007/s00134-009-1695-x. Epub 2009 Oct 17.

Abstract

Introduction: Critically ill patients often develop acute lung injury (ALI) in the context of different clinical conditions. We aimed to explore differences in early local and systemic features in three experimental animal models of ALI.

Methods: Mechanically ventilated male Sprague-Dawley rats were randomized to high tidal volume (VT) ventilation (HVT) (n = 8, VT 24 ml/kg), massive brain injury (MBI) (n = 8, VT 8 ml/kg) or endotoxemia (LPS) (n = 8, VT 8 ml/kg). Each experimental group had its own control group of eight rats (VT 8 ml/kg). We measured arterial blood gases, mean arterial pressure, lung compliance, inflammatory mediators in plasma and their expression and gelatinase activity in the lungs after 3 h of injury.

Results: Despite maintaining relatively normal lung function without evidence of important structural changes, we observed altered lung and systemic inflammatory responses in all three experimental models. LPS triggered the most robust inflammatory response and HVT the lowest systemic proinflammatory response. The HVT group had higher Il6, Tnf and Cxcl2 mRNA in lungs than MBI animals. Metalloproteinase activity/expression and neutrophilic recruitment in the lungs were higher in HVT than in LPS or MBI.

Conclusions: The early responses to direct or remote lung insult in our three models of ALI captured different physiological and biological features that could lead to respiratory and/or multiorgan failure.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Brain Injuries / diagnosis*
  • Brain Injuries / metabolism
  • Brain Injuries / physiopathology*
  • Disease Models, Animal*
  • Endotoxemia / diagnosis
  • Endotoxemia / epidemiology
  • Endotoxemia / physiopathology
  • Lipopolysaccharides / metabolism
  • Male
  • Metalloproteases / metabolism
  • Positive-Pressure Respiration
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Respiration, Artificial
  • Severity of Illness Index
  • Time Factors

Substances

  • Lipopolysaccharides
  • Metalloproteases