Atelectasis Causes Vascular Leak and Lethal Right Ventricular Failure in Uninjured Rat Lungs

Duggan, Michelle; McCaul, Conán; McNamara, Patrick J.; Engelberts, Doreen; Ackerley, Cameron; Kavanagh, Brian P.

doi:10.1164/rccm.200210-1215oc

Cited by 154 publications

(80 citation statements)

References 50 publications

(16 reference statements)

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“…Progressive atelectasis may lead to ventilation-perfusion mismatch, ventilation inhomogeneity, shear stress, and eventually lung injury (Duggan et al, 2003;Lapinsky and Mehta, 2005). When using a volumecontrolled ventilation mode, reduction in lung volume not only results in a fall in compliance and higher peak pressure levels, but also causes lung injury by overdistension…”

Section: Discussionmentioning

confidence: 99%

Lung volume recruitment maneuvers and respiratory system mechanics in mechanically ventilated mice

Cannizzaro

Berry

Nicholls

et al. 2009

Respiratory Physiology & Neurobiology

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Section: Discussionmentioning

confidence: 99%

Lung volume recruitment maneuvers and respiratory system mechanics in mechanically ventilated mice

Cannizzaro

Berry

Nicholls

et al. 2009

Respiratory Physiology & Neurobiology

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“…large V t (22,23)-CO 2 may be less effective in ameliorating injury caused by atelectasis. This may be important with the increasingly recognized spectrum of atelectasis-associated lung injury (35).…”

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confidence: 99%

Therapeutic Hypercapnia Is Not Protective in the in vivo Surfactant-Depleted Rabbit Lung

et al. 2004

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Permissive hypercapnia because of reduced tidal volume is associated with improved survival in lung injury, whereas therapeutic hypercapnia-deliberate elevation of arterial PCO 2 -protects against in vivo reperfusion injury and injury produced by severe lung stretch. No published studies to date have examined the effects of CO 2 on in vivo models of neonatal lung injury. We used an established in vivo rabbit model of surfactant depletion to investigate whether therapeutic hypercapnia would improve oxygenation and protect against ventilator-induced lung injury. Animals were randomized to injurious (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H 2 O) or protective ventilatory strategy (tidal volume, 5 mL/kg; positive end-expiratory pressure, 12.5 cm H 2 O), and to receive either control conditions or therapeutic hypercapnia (fraction of inspired CO 2 , 0.12). Oxygenation (alveolar-arterial O 2 difference, arterial PO 2 ), lung injury (alveolar-capillary protein leak, impairment of static compliance), and selected bronchoalveolar lavage and plasma cytokines (IL-8, growth-related oncogene, monocyte chemoattractant protein-1, and tumor necrosis factor-␣) were measured. Injurious ventilation resulted in a large alveolar-arterial O 2 gradient, elevated peak airway pressure, increased protein leak, and impaired lung compliance. Therapeutic hypercapnia did not affect any of these outcomes. Tumor necrosis factor-␣ was not increased by mechanical stretch in any of the groups. Therapeutic hypercapnia abolished the stretch-induced increase in bronchoalveolar lavage monocyte chemoattractant protein-1, but did not affect any of the other mediators studied. Therapeutic hypercapnia may attenuate the impairment in oxygenation and inhibit certain cytokines. Because hypercapnia inhibits certain cytokines but does not alter lung injury, the pathogenic role of these cytokines in lung injury is questionable. Mechanical ventilation is central to neonatal and pediatric critical care. Limiting V t during mechanical ventilation in the setting of acute lung injury results in several important effects, including elevation of PaCO 2 (1, 2), alteration of lung inflammatory events (3), decreased duration of mechanical ventilation (4), and improved survival (5). Although the associations among these effects are clear, the mechanistic relationships are uncertain. Lung stretch is associated with a complex series of pulmonary and systemic events, including neutrophil recruitment (6) and release of inflammatory prostanoids (7,8) and cytokines (9 -11) as well as morphologic injury (6,12).Alterations in CO 2 tension may be important in this paradigm for several reasons (13

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“…Several differences between the two studies may explain the dissimilar results (34). First, this study used a model of uninjured rat lungs ventilated for a shorter period (2.5 h), a strategy that may minimize lesions associated with the repetition of overdistention and vascular stretch with DI.…”

Section: Discussionmentioning

confidence: 99%

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

Dessap

Voiriot

Zhou

et al. 2012

Am J Respir Cell Mol Biol

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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...

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Atelectasis Causes Vascular Leak and Lethal Right Ventricular Failure in Uninjured Rat Lungs

Cited by 154 publications

References 50 publications

Lung volume recruitment maneuvers and respiratory system mechanics in mechanically ventilated mice

Lung volume recruitment maneuvers and respiratory system mechanics in mechanically ventilated mice

Therapeutic Hypercapnia Is Not Protective in the in vivo Surfactant-Depleted Rabbit Lung

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

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