Laboratory Investigations

Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung

Broche, Ludovic PhD^1,2; Perchiazzi, Gaetano MD, PhD^3,4; Porra, Liisa PhD^5,6; Tannoia, Angela MD⁴; Pellegrini, Mariangela MD^3,4; Derosa, Savino MD⁴; Sindaco, Alessandra MD⁴; Batista Borges, João MD, PhD^3,7; Degrugilliers, Loïc MSc²; Larsson, Anders MD, PhD³; Hedenstierna, Göran MD, PhD⁸; Wexler, Anthony S. PhD⁹; Bravin, Alberto PhD¹; Verbanck, Sylvia PhD¹⁰; Smith, Bradford J. PhD¹¹; Bates, Jason H. T. PhD¹¹; Bayat, Sam MD, PhD²

Author Information

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.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

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.

For information regarding this article, E-mail: [email protected]; [email protected]

Critical Care Medicine 45(4):p 687-694, April 2017. | DOI: 10.1097/CCM.0000000000002234

Abstract

Objectives:

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.

Design:

Experimental animal study.

Setting:

International synchrotron radiation laboratory.

Subjects:

Four anesthetized rabbits, ventilated in pressure controlled mode.

Interventions:

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 (F_derecruited, F_recruited) were computed based on the comparison of the aerated volumes at successive time points.

Measurements and Main Results:

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 F_derecruited and F_recruited when mechanical interdependence was included, while its exclusion gave F_recruited values of zero at positive end-expiratory pressure greater than or equal to 3 cm H₂O.

Conclusions:

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.