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Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung*

Broche, Ludovic PhD1,2; Pisa, Pauline MD3; Porra, Liisa PhD4,5; Degrugilliers, Loïc MSc6; Bravin, Alberto PhD2; Pellegrini, Mariangela MD1; Borges, João Batista MD, PhD1; Perchiazzi, Gaetano MD, PhD1; Larsson, Anders MD, PhD1; Hedenstierna, Göran MD, PhD1; Bayat, Sam MD, PhD7,8

doi: 10.1097/CCM.0000000000003838
Online Laboratory Investigation

Objectives: Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT.

Design: Laboratory animal investigation.

Setting: European synchrotron radiation facility.

Subjects: Six New-Zealand White rabbits.

Interventions: The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; Fio2, 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 × 47.5 × 47.5 μm voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured.

Measurements and Main Results: The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.35 ± 0.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 ± 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001).

Conclusions: Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify “compliant collapse” as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways.

1Hedenstierna Laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

2ID17 Biomedical Beamline, European Synchrotron Radiation Facility (ESRF), Grenoble, France.

3University of Picardie Jules Verne Medical Faculty, Amiens, France.

4Department of Physics, University of Helsinki, Helsinki, Finland.

5Helsinki University Central Hospital, Medical Imaging Center, Helsinki, Finland.

6Department of Pediatric Intensive Care, Amiens University Hospital, Amiens, France.

7University of Grenoble Alpes & Inserm UA7 STROBE Laboratory, Grenoble, France.

8Department of Pulmonology and Physiology, Grenoble University Hospital, Grenoble, France.

*See also p. 1281.

Drs. Broche, Porra, Borges, Perchiazzi, Larsson, Hedenstierna, and Bayat designed the study. Drs. Broche, Pisa, and Porra, Mr. Degrugilliers, and Drs. Bravin, Borges, Perchiazzi, Larsson, and Bayat acquired, analyzed, or interpreted data. Drs. Broche and Bayat drafted the article. All authors critically revised the article prior to submission.

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Supported, in part, by grant from the Swedish Heart and Lung Foundation and the Swedish Research Council (K2015-99X -22731-01-4); supported by the Picardie Regional Council (#Reg08009); European Synchrotron Radiation Facility; Bari University; and Tampere Tuberculosis Foundation Finland.

Dr. Larsson’s institution received funding from Swedish Research Council and Swedish Heart and Lung Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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