Influenza A H1N1 induces declines in alveolar gas exchange in mice consistent with rapid post‐infection progression from acute lung injury to ARDS. Issue 3 (2nd August 2012)

• Record Type: Journal Article
• Authors: Traylor, Zachary P.; Aeffner, Famke; Davis, Ian C.
• Is Part Of: Influenza and other respiratory viruses. Volume 7:Issue 3(2013:May)
• Page Start: 472
• Page End: 479
• Publication Date: 2012-08-02
• Subjects: Influenza -- Periodicals; Respiratory infections -- Periodicals; Virus diseases -- Periodicals; Influenza, Human -- Periodicals; Respiratory Tract Diseases -- Periodicals; Virus Diseases -- Periodicals; Grippe -- Périodiques; Appareil respiratoire -- Infections -- Périodiques; Maladies à virus -- Périodiques; 616.203
• DOI: 10.1111/j.1750-2659.2012.00414.x
• Languages: English
• ISSNs: 1750-2640

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold>Background </bold> Patients with severe seasonal or pandemic influenza pneumonia frequently develop acute respiratory distress syndrome (ARDS). One clinical diagnostic criterion for ARDS is the P<sub>a</sub>O<sub>2</sub>:F<sub>i</sub>O<sub>2</sub> ratio, which is an index of alveolar gas exchange. However, effects of H1N1 influenza infection on P<sub>a</sub>O<sub>2</sub>:F<sub>i</sub>O<sub>2</sub> ratios and related pathophysiologic readouts of lung function have not been reported in mice.</p> <p> <bold>Methods </bold> To develop a method for determining P<sub>a</sub>O<sub>2</sub>:F<sub>i</sub>O<sub>2</sub> 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 (F<sub>i</sub>O<sub>2</sub> = 0·21) or 100% O<sub>2</sub> (F<sub>i</sub>O<sub>2</sub> = 1·0), carotid P<sub>a</sub>O<sub>2</sub> was measured. To determine influenza effects on P<sub>a</sub>O<sub>2</sub>:F<sub>i</sub>O<sub>2</sub>, mice were challenged with 10 000 p.f..u./mouse influenza A/WSN/33.</p> <p> <bold>Results </bold> P<sub>a</sub>O<sub>2</sub>:F<sub>i</sub>O<sub>2</sub> ratios were abnormally low (≤400 mmHg) in spontaneously breathing mice. Mechanical ventilation with positive end‐expiratory pressure was required to obtain P<sub>a</sub>O<sub>2</sub>:F<sub>i</sub>O<sub>2</sub> ratios in uninfected mice consistent with normal values in humans (≥600 mmHg). At day 2 following infection P<sub>a</sub>O<sub>2</sub>:F<sub>i</sub>O<sub>2</sub> ratios indicated the onset of acute lung injury. By day 6, P<sub>a</sub>O<sub>2</sub>:F<sub>i</sub>O<sub>2</sub> ratios were <200 mmHg, indicating progression to ARDS. Impaired gas exchange in influenza‐infected mice was accompanied by progressive hemoglobin desaturation, hypercapnia, uncompensated respiratory acidosis, hyperkalemia, and polycythemia.</p> <p> <bold>Conclusions </bold> Influenza infection of mice results in impairment of alveolar gas exchange consistent with rapid development of acute lung injury and progression to ARDS. P<sub>a</sub>O<sub>2</sub>:F<sub>i</sub>O<sub>2</sub> ratios may be of utility as clinically relevant and predictive outcome measures in influenza pathogenesis and treatment studies that use mouse models.</p> </abstract>