The differential effects of inspiratory, expiratory, and combined resistive breathing on healthy lung

Abstract

Konstantinos Loverdos,1 Dimitrios Toumpanakis,1 Eleni Litsiou,1 Vassiliki Karavana,1 Constantinos Glynos,1 Christina Magkou,2 Stamatios Theocharis,3 Theodoros Vassilakopoulos1 1Department of Critical Care, Pulmonary Unit and Marianthi Simou Applied Biomedical Research and Training Center, Evangelismos General Hospital, University of Athens Medical School, 2Department of Pathology, Evangelismos General Hospital, 31st Department of Pathology, University of Athens Medical School, Athens, Greece 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. Keywords: resistive breathing, lung injury, inflammation

Keywords

• resistive breathing
• lung injury
• inflammation