title: Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model.
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 (Vt) = 7 cc/kg, positive end expiratory pressure (PEEP) = 3 cm H2O; (b) moderate volume, high PEEP (MVHP), Vt = 15 cc/kg; PEEP = 10 cm H2O; (c) moderate volume, zero PEEP (MVZP), Vt = 15 cc/kg, PEEP = 0; or (d) high volume, zero PEEP (HVZP), Vt = 40 cc/kg, PEEP = 0. Ventilation with zero PEEP (MVZP, HVZP) resulted in significant reductions in lung compliance. Lung lavage levels of TNFalpha, IL-1beta, IL-6, IL-10, MIP-2, and IFNgamma 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 TNFalpha versus controls). Identical end inspiratory lung distention with PEEP (MVHP) resulted in only a three-fold increase in TNFalpha, whereas MVZP produced a six-fold increase in lavage TNFalpha. 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.
authors.affiliation: Division of General Surgery, The Toronto Hospital, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Tremblay
authors.forename: F
authors.initials: F
authors.lastname: Valenza
authors.forename: S P
authors.initials: SP
authors.lastname: Ribeiro
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: A S
authors.initials: AS
authors.lastname: Slutsky
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054407:Chemokine CCL4; D004797:Enzyme-Linked Immunosorbent Assay; D016762:Genes, fos; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D007375:Interleukin-1 / Q000032:analysis / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D008170:Lung Compliance; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000276:immunology; D008297:Male; D011175:Positive-Pressure Respiration / Q000009:adverse effects* / Q000379:methods; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: D054407:Chemokine CCL4; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D011506:Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma