Am. J. Respir. Crit. Care Med., Volume 160, Number 1, July 1999, 109-116

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

DAVIDE CHIUMELLO, GORSEV PRISTINE, and ARTHUR S. SLUTSKY

Division of Respiratory Medicine, Mount Sinai Hospital, Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Ontario, Canada

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-] 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- 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.

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