Augmented lung injury due to interaction between hyperoxia and mechanical ventilation

Area of Science:

• Pulmonary Medicine
• Critical Care
• Mechanical Ventilation

Background:

• Mechanical overdistension and hyperoxia are known causes of lung injury.
• The combined effects of high tidal volume ventilation and hyperoxia on lung injury are not well understood.

Purpose of the Study:

• To investigate the hypothesis that hyperoxia exacerbates lung injury induced by large tidal volume ventilation.
• To assess the interaction between tidal volume and inspired oxygen concentration on potential mediators of lung injury.

Main Methods:

• An experimental study using anesthetized, paralyzed rabbits.
• Experiment 1: Ventilation with high tidal volumes (25 mL/kg) under hyperoxia (FiO2 = 0.5) or normoxia (FiO2 = 0.21) for 4 hours.
• Experiment 2: Assessment of mediators of injury after 2 hours of ventilation with varying tidal volumes (10 or 25 mL/kg) and oxygen concentrations (normoxia or hyperoxia).

Main Results:

• Hyperoxia significantly reduced the PaO2/FiO2 ratio and increased lung injury scores at 4 hours compared to normoxia.
• Hyperoxia increased concentrations of polymorphonuclear leukocytes, growth-related oncogene-alpha, and monocyte chemotactic protein-1 in bronchoalveolar lavage fluid.
• Increased alveolar-capillary permeability was observed only with the combination of hyperoxia and high tidal volume ventilation.

Conclusions:

• Moderate hyperoxia exacerbates ventilator-induced lung injury in a model using large tidal volumes.
• The mechanism of hyperoxia-induced exacerbation of lung injury does not appear to involve increased CXC chemokines or lipid peroxidation.