Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model

Lorraine Tremblay, Franco Valenza, Sergio P. Ribeiro, Jingfang Li, Arthur S. Slutsky

Research output: Contribution to journalArticle

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Abstract

We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus. 55 Sprague-Dawley rats were randomized to either intravenous saline or lipopolysaccharide (LPS). After 50 min of spontaneous respiration, the lungs were excised and randomized to 2 h of ventilation with one of four strategies: (a) control (C), tidal volume (V(t)) = 7 cc/kg, positive end expiratory pressure (PEEP) = 3 cm H2O; (b) moderate volume, high PEEP (MVHP), V(t) = 15 cc/kg; PEEP = 10 cm H2O; (c) moderate volume, zero PEEP (MVZP), V(t) = 15 cc/kg, PEEP = 0; or (d) high volume, zero PEEP (HVZP), V(t) = 40 cc/kg, PEEP = 0. Ventilation with zero PEEP (MVZP, HVZP) resulted in significant reductions in lung compliance. Lung lavage levels of TNFα, IL- 1β, IL-6, IL-10, MIP-2, and IFNγ were measured by ELISA. Zero PEEP in combination with high volume ventilation (HVZP) had a synergistic effect on cytokine levels (e.g., 56-fold increase of TNFα versus controls). Identical end inspiratory lung distention with PEEP (MVHP) resulted in only a three- fold increase in TNFα, whereas MVZP produced a six-fold increase in lavage TNFα. Northern blot analysis revealed a similar pattern (C, MVHP <MVZP <HVZP) for induction of c-fos mRNA. These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung, and thus may play a role in initiating or propagating a local, and possibly systemic inflammatory response.

Original languageEnglish
Pages (from-to)944-952
Number of pages9
JournalJournal of Clinical Investigation
Volume99
Issue number5
Publication statusPublished - Mar 1 1997

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Positive-Pressure Respiration
RNA
Cytokines
Lung
Ventilation
Lung Compliance
Therapeutic Irrigation
Tidal Volume
Bronchoalveolar Lavage
Interleukin-1
Artificial Respiration
Northern Blotting
Interleukin-10
Sprague Dawley Rats
Lipopolysaccharides
Interleukin-6
Respiration
Anti-Inflammatory Agents
Enzyme-Linked Immunosorbent Assay
Messenger RNA

Keywords

  • artificial
  • bronchoalveolar lavage fluid
  • inflammation
  • leukotrienes
  • respiration
  • tumor necrosis factor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. / Tremblay, Lorraine; Valenza, Franco; Ribeiro, Sergio P.; Li, Jingfang; Slutsky, Arthur S.

In: Journal of Clinical Investigation, Vol. 99, No. 5, 01.03.1997, p. 944-952.

Research output: Contribution to journalArticle

Tremblay, Lorraine ; Valenza, Franco ; Ribeiro, Sergio P. ; Li, Jingfang ; Slutsky, Arthur S. / Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. In: Journal of Clinical Investigation. 1997 ; Vol. 99, No. 5. pp. 944-952.
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AB - We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus. 55 Sprague-Dawley rats were randomized to either intravenous saline or lipopolysaccharide (LPS). After 50 min of spontaneous respiration, the lungs were excised and randomized to 2 h of ventilation with one of four strategies: (a) control (C), tidal volume (V(t)) = 7 cc/kg, positive end expiratory pressure (PEEP) = 3 cm H2O; (b) moderate volume, high PEEP (MVHP), V(t) = 15 cc/kg; PEEP = 10 cm H2O; (c) moderate volume, zero PEEP (MVZP), V(t) = 15 cc/kg, PEEP = 0; or (d) high volume, zero PEEP (HVZP), V(t) = 40 cc/kg, PEEP = 0. Ventilation with zero PEEP (MVZP, HVZP) resulted in significant reductions in lung compliance. Lung lavage levels of TNFα, IL- 1β, IL-6, IL-10, MIP-2, and IFNγ were measured by ELISA. Zero PEEP in combination with high volume ventilation (HVZP) had a synergistic effect on cytokine levels (e.g., 56-fold increase of TNFα versus controls). Identical end inspiratory lung distention with PEEP (MVHP) resulted in only a three- fold increase in TNFα, whereas MVZP produced a six-fold increase in lavage TNFα. Northern blot analysis revealed a similar pattern (C, MVHP <MVZP <HVZP) for induction of c-fos mRNA. These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung, and thus may play a role in initiating or propagating a local, and possibly systemic inflammatory response.

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