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Regional Lung Mechanics and Influence of an Active Diaphragm in Experimental Lung Injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.ORCID iD: 0000-0001-5668-7399
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Despite being an essential life-support strategy in severe respiratory failure, mechanical ventilation can, if not optimally set and monitored, lead to injury of the lung parenchyma and diaphragm. These conditions are called ventilator-induced lung injury and ventilator-induced diaphragmatic dysfunction (VIDD), respectively. Although substantial progress has been made in the ventilator management of severely lung-injured patients, we are still far from a fully protective mechanical ventilation. In consideration of this gap of knowledge, this doctoral thesis aimed at investigating regional lung mechanics during both inspiration and expiration, in both controlled and assisted ventilation. Particular emphasis was placed on the expiratory phase, which is involved in expiratory flow limitation, airway closure and atelectasis formation, although commonly considered non-harmful.

A novel methodological approach has been the fundamental basis for this research project. The combination of respiratory mechanics, diaphragmatic electromyographic activity and lung imaging enabled a breath-by-breath analysis at high temporal and spatial resolution.

In Study I, the gravitational field affected the distribution of gas and transpulmonary pressures, as previously shown. This effect differed between healthy and injured lungs. Moreover, lung injury induced a heterogeneous distribution of gas within the lungs, as well as an increased gravitational gradient in transpulmonary pressure. Study I was mainly aimed at testing the new methodological approach centred on the investigation of regional lung mechanics.

In Study II, the focus was on assisted ventilation and the phenomenon of gas redistribution within the lungs. Large pendelluft events had been demonstrated in disproportionate inspiratory efforts. In Study II, we showed that large pendelluft resulting from pathological respiratory drive could be attenuated by high positive end expiratory pressure (PEEP). Moreover, we showed that transient and widespread small gas redistribution events occur at all times during inspiration. Assisted ventilation and high PEEP reduced the size of gas redistribution as compared with controlled ventilation and low PEEP.

In Study III, we demonstrated a diaphragmatic expiratory contraction in lungs prone to collapse, serving to brake the expiratory flow. It preserved end expiratory lung volume (EELV) and counteracted tidal atelectasis. However, the expiratory brake induced by diaphragmatic contraction is a known cause of VIDD.

In Study IV, we tested the effects of external expiratory resistances (ExpR). We showed that, by applying ExpR, an expiratory brake was induced. The beneficial effects on EELV were retained, while the diaphragm could quickly relax during the expiration, thus reducing the risk of VIDD.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 80
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1606
Keywords [en]
acute respiratory distress syndrome, artificial respiration, diaphragm, pulmonary atelectasis, lung imaging, respiratory system, animal model
National Category
Anesthesiology and Intensive Care Physiology Respiratory Medicine and Allergy
Research subject
Physiology; Anaesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-394305ISBN: 978-91-513-0790-9 (print)OAI: oai:DiVA.org:uu-394305DiVA, id: diva2:1358542
Public defence
2019-12-16, Akademiska sjukhuset, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2019-11-22 Created: 2019-10-07 Last updated: 2019-11-27
List of papers
1. Effects of superimposed tissue weight on regional compliance of injured lungs
Open this publication in new window or tab >>Effects of superimposed tissue weight on regional compliance of injured lungs
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2016 (English)In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 228, p. 16-24Article in journal (Refereed) Published
Abstract [en]

Computed tomography (CT), together with image analysis technologies, enable the construction of regional volume (V-REG) and local transpulmonary pressure (P-TP,P-REG) maps of the lung. Purpose of this study is to assess the distribution of V-REG vs P-TP,P-REG along the gravitational axis in healthy (HL) and experimental acute lung injury conditions (eALI) at various positive end-expiratory pressures (PEEPS) and inflation volumes. Mechanically ventilated pigs underwent inspiratory hold maneuvers at increasing volumes simultaneously with lung CT scans. eALI was induced via the iv administration of oleic acid. We computed voxel-level V-REG vs P-TP,P-REG curves into eleven isogravitational planes by applying polynomial regressions. Via F-test, we determined that V-REG vs P-TP,P-REG curves derived from different anatomical planes (p-values < 1.4E-3), exposed to different PEEPs (p-values < 1.5E-5) or subtending different lung status (p-values < 3E-3) were statistically different (except for two cases of adjacent planes). Lung parenchyma exhibits different elastic behaviors based on its position and the density of superimposed tissue which can increase during lung injury.

Keywords
Lung compliance, Computed tomography, Acute lung injury, Image registration, Mechanical ventilation, Gravity
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-298837 (URN)10.1016/j.resp.2016.03.005 (DOI)000376832900003 ()26976688 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2016-07-11 Created: 2016-07-11 Last updated: 2019-10-07Bibliographically approved
2. Transients of Air‐Redistribution Characterize Both Spontaneous Breathing and Mechanical Ventilation
Open this publication in new window or tab >>Transients of Air‐Redistribution Characterize Both Spontaneous Breathing and Mechanical Ventilation
(English)In: Article in journal (Refereed) Submitted
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-394304 (URN)
Available from: 2019-10-07 Created: 2019-10-07 Last updated: 2019-10-07
3. The Diaphragm Acts as a Brake During Expiration to Prevent Lung Collapse
Open this publication in new window or tab >>The Diaphragm Acts as a Brake During Expiration to Prevent Lung Collapse
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2017 (English)In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, no 12, p. 1608-1616Article in journal (Refereed) Published
Abstract [en]

Rationale: The diaphragm is the major inspiratory muscle and is assumed to relax during expiration. However, electrical postinspiratory activity has been observed. Whether there is an expiratory diaphragmatic contraction that preserves lung patency has yet to be explored.

Objectives: We hypothesized the occurrence of an expiratory diaphragmatic contraction directed at stabilizing peripheral airways and preventing or reducing cyclic expiratory lung collapse.

Methods: Mild acute respiratory distress syndrome was induced in 10 anesthetized, spontaneously breathing pigs. Lung volume was decreased by lowering end-expiratory airway pressure in a stepwise manner. We recorded the diaphragmatic electric activity during expiration, dynamic computed tomographic scans, and respiratory mechanics. In five pigs, the same protocol was repeated during mechanical ventilation after muscle paralysis.

Measurements and Main Results: Diaphragmatic electric activity during expiration increased by decreasing end-expiratory lung volume during spontaneous breathing. This enhanced the diaphragm muscle force, to a greater extent with lower lung volume, indicating a diaphragmatic electromechanical coupling during spontaneous expiration. In turn, the resulting diaphragmatic contraction delayed and reduced the expiratory collapse and increased lung aeration compared with mechanical ventilation with muscle paralysis and absence of diaphragmatic activity.

Conclusions: The diaphragm is an important regulator of expiration. Its expiratory activity seems to preserve lung volume and to protect against lung collapse. The loss of diaphragmatic expiratory contraction during mechanical ventilation and muscle paralysis may be a contributing factor to unsuccessful respiratory support.

National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-312488 (URN)10.1164/rccm.201605-0992OC (DOI)000403383600015 ()27922742 (PubMedID)
Funder
Swedish Research Council, X2015-99x-22731-01-4Swedish Heart Lung Foundation
Available from: 2017-01-10 Created: 2017-01-10 Last updated: 2019-10-07Bibliographically approved
4. Expiratory Resistance Prevents Eccentric Diaphragm Contraction, Flow Limitation andLung Collapse
Open this publication in new window or tab >>Expiratory Resistance Prevents Eccentric Diaphragm Contraction, Flow Limitation andLung Collapse
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(English)In: Article in journal (Refereed) Submitted
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-394303 (URN)
Available from: 2019-10-07 Created: 2019-10-07 Last updated: 2019-10-07

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