Influenza A H1N1 induces declines in alveolar gas exchange in mice consistent with rapid post-infection progression from acute lung injury to ARDS
Open Access
- 2 August 2012
- journal article
- research article
- Published by Wiley in Influenza and Other Respiratory Viruses
- Vol. 7 (3), 472-479
- https://doi.org/10.1111/j.1750-2659.2012.00414.x
Abstract
Background Patients with severe seasonal or pandemic influenza pneumonia frequently develop acute respiratory distress syndrome (ARDS). One clinical diagnostic criterion for ARDS is the PaO2:FiO2 ratio, which is an index of alveolar gas exchange. However, effects of H1N1 influenza infection on PaO2:FiO2 ratios and related pathophysiologic readouts of lung function have not been reported in mice. Methods To develop a method for determining PaO2:FiO2 ratios, uninfected mice were anesthetized with pentobarbital, diazepam/ketamine, or inhaled isoflurane. Subsequently, they were allowed to breathe spontaneously or were mechanically ventilated. After 15 minutes exposure to room air (FiO2 = 0·21) or 100% O2 (FiO2 = 1·0), carotid PaO2 was measured. To determine influenza effects on PaO2:FiO2, mice were challenged with 10 000 p.f..u./mouse influenza A/WSN/33. Results PaO2:FiO2 ratios were abnormally low (≤400 mmHg) in spontaneously breathing mice. Mechanical ventilation with positive end-expiratory pressure was required to obtain PaO2:FiO2 ratios in uninfected mice consistent with normal values in humans (≥600 mmHg). At day 2 following infection PaO2:FiO2 ratios indicated the onset of acute lung injury. By day 6, PaO2:FiO2 ratios were aO2:FiO2 ratios may be of utility as clinically relevant and predictive outcome measures in influenza pathogenesis and treatment studies that use mouse models.Keywords
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