title: Carbon dioxide attenuates pulmonary impairment resulting from hyperventilation.
abstract: OBJECTIVE
  Deliberate elevation of PaCO2 (therapeutic hypercapnia) protects against lung injury induced by lung reperfusion and severe lung stretch. Conversely, hypocapnic alkalosis causes lung injury and worsens lung reperfusion injury. Alterations in lung surfactant may contribute to ventilator-associated lung injury. The potential for CO2 to contribute to the pathogenesis of ventilator-associated lung injury at clinically relevant tidal volumes is unknown. We hypothesized that: 1) hypocapnia would worsen ventilator-associated lung injury, 2) therapeutic hypercapnia would attenuate ventilator-associated lung injury; and 3) the mechanisms of impaired compliance would be via alteration of surfactant biochemistry.
  
  
  METHODS
  Randomized, prospective animal study.
  
  
  METHODS
  Research laboratory of university-affiliated hospital.
  
  
  METHODS
  Anesthetized, male New Zealand Rabbits.
  
  
  METHODS
  All animals received the same ventilation strategy (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O; rate, 42 breaths/min) and were randomized to receive FiCO2 of 0.00, 0.05, or 0.12 to produce hypocapnia, normocapnia, and hypercapnia, respectively.
  
  
  RESULTS
  Alveolar-arterial oxygen gradient was significantly lower with therapeutic hypercapnia, and peak airway pressure was significantly higher with hypocapnic alkalosis. However, neither static lung compliance nor surfactant chemistry (total surfactant, aggregates, or composition) differed among the groups.
  
  
  CONCLUSIONS
  At clinically relevant tidal volume, CO2 modulates key physiologic indices of lung injury, including alveolar-arterial oxygen gradient and airway pressure, indicating a potential role in the pathogenesis of ventilator-associated lung injury. These effects are surfactant independent.
authors: Lung Biology Program, The Research Institute and Department of Critical Care Medicine and Anesthesia, Hospital for Sick Children, Interdepartmental Division of Critical Care, University of Toronto, Ontario, Canada.
authors: John G
authors: JG
authors: Laffey
authors: Doreen
authors: D
authors: Engelberts
authors: Michelle
authors: M
authors: Duggan
authors: Ruud
authors: R
authors: Veldhuizen
authors: James F
authors: JF
authors: Lewis
authors: Brian P
authors: BP
authors: Kavanagh
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000009:adverse effects / Q000627:therapeutic use*; D006985:Hyperventilation; D016857:Hypocapnia / Q000150:complications* / Q000503:physiopathology; D008297:Male; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000628:therapy; D013990:Tidal Volume
chemical_list: D002245:Carbon Dioxide