Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model.
Experimental animal study.
International synchrotron radiation laboratory.
Four anesthetized rabbits, ventilated in pressure controlled mode.
The lung was consecutively imaged at ~ 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end-expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (Fderecruited, Frecruited) were computed based on the comparison of the aerated volumes at successive time points.
Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of Fderecruited and Frecruited when mechanical interdependence was included, while its exclusion gave Frecruited values of zero at positive end-expiratory pressure greater than or equal to 3 cm H2O.
These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.
1European Synchrotron Radiation Facility, ID17 Biomedical Beamline, Grenoble, France.
2Department of Pediatric Pulmonology, Université de Picardie Jules Verne, Inserm U1105 & Amiens University Hospital, Amiens, France.
3Hedenstierna Laboratory, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Uppsala, Sweden.
4Department of Emergency and Organ Transplant, University of Bari, Bari, Italy.
5Department of Physics, University of Helsinki, Helsinki, Finland.
6Helsinki University Central Hospital, Helsinki, Finland.
7Pulmonary Division, Cardio-Pulmonary Department, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil.
8Hedenstierna Laboratory, Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.
9Department of Mechanical Engineering and Environmental Quality Laboratory, University of California Davis, Davis, CA.
10Respiratory Division, University Hospital UZ Brussel, Brussels, Belgium.
11Department of Medicine, University of Vermont, Burlington, VT.
Work performed at the European Synchrotron Radiation Facility.
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Supported, in part, by the Swedish Heart, the Lung foundation and the Swedish Research Council (K2015-99X-22731-01-4); the Picardie Regional Council; the European Synchrotron Radiation Facility; the Bari University; the Tampere Tuberculosis Foundation Finland; and the United States National Institutes of Health (1 R01 HL124052 and 1 K99 HL128944).
Dr. Broche received support for article research from the Picardie Regional Council and the European Synchrotron Radiation Facility. Dr. Porra received support received support for article research from the Tampere Tuberculosis Foundation Finland. Dr. Perchiazzi received support for article research from the Bari University. Dr. Larsson received support for article research from the Swedish Research Council (Vetenskapsrådet-VR). His institution received funding from the Swedish Research Council and from the Swedish Heart and Lung Foundation. Dr. Smith received support for article research from the National Institutes of Health (NIH). Dr. Bates received support for article research from the NIH. His institution received funding from the NIH-National Heart, Lung and Blood Institute. Dr. Bayat received funding from Novartis pharmaceuticals (one-time fee for lecture). The remaining authors have disclosed that they do not have any potential conflicts of interest.
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