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 language | English |
|---|---|
| Pages (from-to) | 944-952 |
| Number of pages | 9 |
| Journal | Journal of Clinical Investigation |
| Volume | 99 |
| Issue number | 5 |
| Publication status | Published - Mar 1 1997 |
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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 journal › Article
}
TY - JOUR
T1 - Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model
AU - Tremblay, Lorraine
AU - Valenza, Franco
AU - Ribeiro, Sergio P.
AU - Li, Jingfang
AU - Slutsky, Arthur S.
PY - 1997/3/1
Y1 - 1997/3/1
N2 - 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.
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.
KW - artificial
KW - bronchoalveolar lavage fluid
KW - inflammation
KW - leukotrienes
KW - respiration
KW - tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=0030981335&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030981335&partnerID=8YFLogxK
M3 - Article
C2 - 9062352
AN - SCOPUS:0030981335
VL - 99
SP - 944
EP - 952
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 5
ER -