Mechanical Ventilation Affects Local and Systemic Cytokines in an Animal Model of Acute Respiratory Distress Syndrome

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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 (Fi O2 ) was 1. Cytokine concentrations (tumor necrosis factor-alpha [TNF- α ] 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- α 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.