title: The differential effects of inspiratory, expiratory, and combined resistive breathing on healthy lung.
abstract: Combined resistive breathing (CRB) is the hallmark of obstructive airway disease pathophysiology. We have previously shown that severe inspiratory resistive breathing (IRB) induces acute lung injury in healthy rats. The role of expiratory resistance is unknown. The possibility of a load-dependent type of resistive breathing-induced lung injury also remains elusive. Our aim was to investigate the differential effects of IRB, expiratory resistive breathing (ERB), and CRB on healthy rat lung and establish the lowest loads required to induce injury. Anesthetized tracheostomized rats breathed through a two-way valve. Varying resistances were connected to the inspiratory, expiratory, or both ports, so that the peak inspiratory pressure (IRB) was 20%-40% or peak expiratory (ERB) was 40%-70% of maximum. CRB was assessed in inspiratory/expiratory pressures of 30%/50%, 40%/50%, and 40%/60% of maximum. Quietly breathing animals served as controls. At 6 hours, respiratory system mechanics were measured, and bronchoalveolar lavage was performed for measurement of cell and protein concentration. Lung tissue interleukin-6 and interleukin-1β levels were estimated, and a lung injury histological score was determined. ERB produced significant, load-independent neutrophilia, without mechanical or permeability derangements. IRB 30% was the lowest inspiratory load that provoked lung injury. CRB increased tissue elasticity, bronchoalveolar lavage total cell, macrophage and neutrophil counts, protein and cytokine levels, and lung injury score in a dose-dependent manner. In conclusion, CRB load dependently deranges mechanics, increases permeability, and induces inflammation in healthy rats. ERB is a putative inflammatory stimulus for the lung.
authors: Department of Critical Care, Pulmonary Unit and Marianthi Simou Applied Biomedical Research and Training Center, Evangelismos General Hospital, University of Athens Medical School.
authors: Konstantinos
authors: K
authors: Loverdos
authors: Department of Critical Care, Pulmonary Unit and Marianthi Simou Applied Biomedical Research and Training Center, Evangelismos General Hospital, University of Athens Medical School.
authors: Dimitrios
authors: D
authors: Toumpanakis
authors: Department of Critical Care, Pulmonary Unit and Marianthi Simou Applied Biomedical Research and Training Center, Evangelismos General Hospital, University of Athens Medical School.
authors: Eleni
authors: E
authors: Litsiou
authors: Department of Critical Care, Pulmonary Unit and Marianthi Simou Applied Biomedical Research and Training Center, Evangelismos General Hospital, University of Athens Medical School.
authors: Vassiliki
authors: V
authors: Karavana
authors: Department of Critical Care, Pulmonary Unit and Marianthi Simou Applied Biomedical Research and Training Center, Evangelismos General Hospital, University of Athens Medical School.
authors: Constantinos
authors: C
authors: Glynos
authors: Department of Pathology, Evangelismos General Hospital.
authors: Christina
authors: C
authors: Magkou
authors: 1st Department of Pathology, University of Athens Medical School, Athens, Greece.
authors: Stamatios
authors: S
authors: Theocharis
authors: Department of Critical Care, Pulmonary Unit and Marianthi Simou Applied Biomedical Research and Training Center, Evangelismos General Hospital, University of Athens Medical School.
authors: Theodoros
authors: T
authors: Vassilakopoulos
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000403:Airway Resistance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D045853:Exhalation; D015633:Extravascular Lung Water / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D001239:Inhalation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology / Q000503:physiopathology; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology; D017208:Rats, Wistar; D013997:Time Factors; D014939:Work of Breathing
chemical_list: C000594089:IL1B protein, rat; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D009195:Peroxidase
keywords: inflammation; lung injury; resistive breathing