title: Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome.
abstract: We examined the hypothesis that injurious ventilatory strategies (large tidal volume [VT] and/or low positive end-expiratory pressure [PEEP]) would increase release of inflammatory mediators into the lung and into the systemic circulation in a lung injury model. Lung injury was induced in 40 anesthetized paralyzed Sprague-Dawley rats (350 +/- 2 g) by hydrochloric acid instillation (pH 1.5, 2.5 ml/kg). Rats were then randomized into five groups (n = 8): (1) high-volume zero PEEP (HVZP): VT, 16 ml/ kg; (2) high-volume PEEP (HVP): VT, 16 ml/kg, PEEP, 5 cm H2O; (3) low-volume zero PEEP (LVZP): VT, 9 ml/kg; (4) low-volume PEEP (LVP): VT, 9 ml/kg, PEEP, 5 cm H2O; (5) same settings as (4) plus a recruitment maneuver performed every hour (LVPR). Respiratory rate was adjusted to maintain normocapnia and fraction of inspired oxygen (FIO2) was 1. Cytokine concentrations (tumor necrosis factor-alpha [TNF-alpha] and macrophage inflammatory protein-2 [MIP-2]) were measured by ELISA. All animals in the LVZP group died before the end of the experiment. After 4 h of ventilation, the HVZP group had similar lung fluid TNF-alpha concentrations compared with the HVP group: 1,861 +/- 333 pg/ml versus 1,259 +/- 189 pg/ml; and much higher serum concentrations: 692 +/- 74 pg/ml versus 102 +/- 31 pg/ml (p < 0.05). An identical pattern was found for MIP-2. These results suggest that the particular ventilatory strategy can affect the release of cytokines into the systemic circulation, a finding that may have relevance for the development of multisystem organ failure.
authors.affiliation: Division of Respiratory Medicine, Mount Sinai Hospital, Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Chiumello
authors.forename: G
authors.initials: G
authors.lastname: Pristine
authors.forename: A S
authors.initials: AS
authors.lastname: Slutsky
mesh_terms: D000818:Animals; D054426:Chemokine CXCL2; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood*; D008168:Lung / Q000276:immunology; D015846:Monokines / Q000097:blood; D009102:Multiple Organ Failure / Q000276:immunology; D011175:Positive-Pressure Respiration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000276:immunology*; D015656:Respiratory Mechanics / Q000276:immunology; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D016207:Cytokines; D018836:Inflammation Mediators; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha