Hypercapnic acidosis modulates inflammation, lung mechanics, and edema in the isolated perfused lung

J Crit Care. 2007 Dec;22(4):305-13. doi: 10.1016/j.jcrc.2006.12.002. Epub 2007 Mar 30.


Objective: Low tidal volume (V(T)) ventilation strategies may be associated with permissive hypercapnia, which has been shown by ex vivo and in vivo studies to have protective effects. We hypothesized that hypercapnic acidosis may be synergistic with low V(T) ventilation; therefore, we studied the effects of hypercapnia and V(T) on unstimulated and lipopolysaccharide-stimulated isolated perfused lungs.

Materials and methods: Isolated perfused rat lungs were ventilated for 2 hours with low (7 mL/kg) or moderately high (20 mL/kg) V(T) and 5% or 20% CO(2), with lipopolysaccharide or saline added to the perfusate.

Results: Hypercapnia resulted in reduced pulmonary edema, lung stiffness, tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the lavage and perfusate. The moderately high V(T) did not cause lung injury but increased lavage IL-6 and perfusate IL-6 as well as TNF-alpha. Pulmonary edema and respiratory mechanics improved, possibly as a result of a stretch-induced increase in surfactant turnover. Lipopolysaccharide did not induce significant lung injury.

Conclusions: We conclude that hypercapnia exerts a protective effect by modulating inflammation, lung mechanics, and edema. The moderately high V(T) used in this study stimulated inflammation but paradoxically improved edema and lung mechanics with an associated increase in surfactant release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Respiratory / metabolism*
  • Animals
  • Cytokines / metabolism
  • Hypercapnia / metabolism*
  • Inflammation
  • Lipopolysaccharides
  • Lung / blood supply
  • Lung / metabolism*
  • Male
  • Pulmonary Edema / prevention & control*
  • Pulmonary Surfactants / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Respiration, Artificial / methods*
  • Respiratory Mechanics


  • Cytokines
  • Lipopolysaccharides
  • Pulmonary Surfactants