Fluid restriction reduces pulmonary edema in a model of acute lung injury in mechanically ventilated rats

PLoS One. 2019 Jan 17;14(1):e0210172. doi: 10.1371/journal.pone.0210172. eCollection 2019.

Abstract

Experimental acute lung injury models are often used to increase our knowledge on the acute respiratory distress syndrome (ARDS), however, existing animal models often do not take into account the impact of specific fluid strategies on the development of lung injury. In contrast, the current literature strongly suggests that fluid management strategies have a significant impact on clinical outcome of patients with ARDS. Thus, it is important to characterize the role of fluid management strategies in experimental models of lung injury. In this study we investigated the effect of two different fluid strategies on commonly used outcome variables in a short-term model of acute lung injury, in relation to age. Infant (2-3 weeks) and adult (3-4 months) Wistar rats received intratracheal instillations of lipopolysaccharide and 24 hours later were mechanically ventilated for 6 hours. During mechanical ventilation, rats from both age groups were randomized to either a standard or conservative intravenous fluid strategy. We found that the hemodynamic response in infant and adult rats was similar in both fluid strategies. Lung wet-to-dry ratios were lower in adult, but not in infant rats receiving the conservative fluid strategy as compared to the standard fluid strategy. There were age-related differences in markers of alveolar capillary barrier disruption and alveolar fluid clearance, yet these were unaffected by fluid strategy. Finally, we found significantly higher IL-1β and TNF-α concentrations in the adult rats treated with the conservative as compared to the standard fluid regimen. In conclusion, the choice of fluid strategy in mechanically ventilated rats with experimental LPS-induced acute lung injury has a significant effect on pulmonary extravascular water, an important and well-recognized lung injury marker, and on the local pro-inflammatory cytokine profiles. We advocate the use of a more uniform, conservative, fluid strategy regimen in experimental models of acute lung injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / pathology
  • Acute Lung Injury / therapy*
  • Age Factors
  • Animals
  • Animals, Newborn
  • Conservative Treatment / methods*
  • Disease Models, Animal
  • Extravascular Lung Water / metabolism
  • Female
  • Fluid Therapy / methods*
  • Humans
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / toxicity
  • Lung / pathology
  • Male
  • Pulmonary Edema / etiology
  • Pulmonary Edema / pathology
  • Pulmonary Edema / therapy*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Respiration, Artificial*
  • Specific Pathogen-Free Organisms
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • IL1B protein, rat
  • Interleukin-1beta
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha

Grants and funding

This research was supported by the Ammodo Foundation and the Foundation of Pediatric Intensive Care (SKIC) in the Netherlands. This publication was also funded in part by the NIH. The sponsors had no role in the design and execution of the research, the writing of the report or the decision to submit the manuscript for publication.