Conflicting Physiological and Genomic Cardiopulmonary Effects of Recruitment Maneuvers in Murine Acute Lung Injury

Abstract

Low tidal volume ventilation, although promoting atelectasis, is a protective strategy against ventilator-induced lung injury. Deep inflation (DI) recruitment maneuvers restore lung volumes, but potentially compromise lung parenchymal and vascular function via repetitive overdistention. Our objective was to examine cardiopulmonary physiological and transcriptional consequences of recruitment maneuvers. C57/BL6 mice challenged with either PBS or LPS via aspiration were placed on mechanical ventilation (5 h) using low tidal volume inflation (TI; 8 ml/g) alone or in combination with intermittent DIs (0.75 ml twice/min). Lung mechanics during TI ventilation significantly deteriorated, as assessed by forced oscillation technique and pressure-volume curves. DI mitigated the TI-induced alterations in lung mechanics, but induced a significant rise in right ventricle systolic pressures and pulmonary vascular resistances, especially in LPSchallenged animals. In addition, DI exacerbated the LPS-induced genome-wide lung inflammatory transcriptome, with prominent dysregulation of a gene cluster involving vascular processes, as well as increases in cytokine concentrations in bronchoalveolar lavage fluid and plasma. Gene ontology analyses of right ventricular tissue expression profiles also identified inflammatory signatures, as well as apoptosis and membrane organization ontologies, as potential elements in the response to acute pressure overload. Our results, although confirming the improvement in lung mechanics offered by DI, highlight a detrimental impact in sustaining inflammatory response and exacerbating lung vascular dysfunction, events contributing to increases in right ventricle afterload. These novel insights should be integrated into the clinical assessment of the risk/benefit of recruitment maneuver strategies.Keywords: mechanical ventilation; microarray; pulmonary hypertension; right ventricle; acute lung injury Studies demonstrating lower mortality rates in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) receiving low tidal volume ventilation (1, 2) have resulted in adoption of these ventilation guidelines in clinical practice (3). However, low tidal volume ventilation also promotes atelectasis (4), with the potential to worsen lung injury through local alveolar hypoxia, increases in lung permeability (5), and lung inflammation (6). Local intrapulmonary shear forces generated during repeated reopening of atelectatic alveoli may also accelerate injury (7). Deep inflation (DI) recruitment maneuvers have been proposed as a means of periodically reopening regions of atelectasis. Experimental and clinical studies have demonstrated improvement in oxygenation, ventilation, and lung mechanical function after DI, without evidence of lung injury (8, 9). However, several adverse cardiovascular effects have been noted with lung recruitment maneuvers, with both high intrathoracic pressures (potentially leading to a decrease in systemic venous return) and high transpulmonary pressures (wit...

Haemodynamic Effects of Lung Recruitment Manoeuvres

“…It has been demonstrated in a murine model of acute lung injury induced by Escherichia coli lipopolysaccharide that dynamic inflation applied during lung recruitment produced increased right ventricular pressure and total PVR. It also resulted in sustained inflammation and vascular dysfunction whilst no similar changes were reported in healthy lungs [ 19 ].…”

Effects of positive end-expiratory pressure and recruitment maneuvers in a ventilator-induced injury mouse model

“…[ 16 ] Mouse studies have focused on supraphysiologic tidal volumes of 20 to 45 ml/kg to stimulate an injurious response with durations of ventilation varying from two to six hours. [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ] and lung injury has been shown to occur with short-term ventilation. However, a direct comparison between short-term and long-term ventilation in a translational model is currently lacking in the literature and it is also unknown at what time point ventilation becomes injurious.…”

High-frequency oscillatory ventilation and acute respiratory distress syndrome: at the crossroads?

“…The results of OSCAR and OSCILLATE will be a disappointment for proponents of HFOV; however, it is too early to abandon this therapy from the armamentarium of ARDS strategies. Future studies should focus on selection of patients likely to benefit from this intervention and on careful titration of mean airway pressures probably without sustained high inflation pressure recruitment manoeuvres 19 20. Novel techniques of measuring recruitment such as electrical impedance tomography, ultrasound, bedside CT scanning, transpulmonary pressure, or inflammatory cytokines may have a role to play in optimising recruitment and tidal volumes while minimising adverse effects on cardiac function.…”