mTORC1 is a mechanosensor that regulates surfactant function and lung compliance during ventilator-induced lung injury

Background. Mechanical ventilation (MV) has the potential to initiate ventilator-induced lung injury (VILI). The pathogenesis of VILI has been primarily studied in animal models using more or less injurious ventilator settings. However, we speculate that duration of MV also influences severity and character of VILI.Methods. Sixty-four healthy C57Bl/6 mice were mechanically ventilated for 5 or 12 hours, using lower tidal volumes with positive end-expiratory pressure (PEEP) or higher tidal volumes without PEEP. Fifteen nonventilated mice served as controls.Results. All animals remained hemodynamically stable and survived MV protocols. In both MV groups, PaO2to FiO2ratios were lower and alveolar cell counts were higher after 12 hours of MV compared to 5 hours. Alveolar-capillary permeability was increased after 12 hours compared to 5 hours, although differences did not reach statistical significance. Lung levels of inflammatory mediators did not further increase over time. Only in mice ventilated with increased strain, lung compliance declined and wet to dry ratio increased after 12 hours of MV compared to 5 hours.Conclusions. Deleterious effects of MV are partly dependent on its duration. Even lower tidal volumes with PEEP may initiate aspects of VILI after 12 hours of MV.

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Therapeutic Efficacy of Human Mesenchymal Stromal Cells in the Repair of Established Ventilator-induced Lung Injury in the Rat

Anesthesiology ◽

10.1097/aln.0000000000000545 ◽

2015 ◽

Vol 122 (2) ◽

pp. 363-373 ◽

Cited By ~ 39

Author(s):

Mairead Hayes ◽

Claire Masterson ◽

James Devaney ◽

Frank Barry ◽

Steve Elliman ◽

...

Keyword(s):

Lung Injury ◽

Stromal Cells ◽

Therapeutic Potential ◽

Keratinocyte Growth Factor ◽

Lung Compliance ◽

Human Mscs ◽

Lung Repair ◽

Ventilator Induced Lung Injury ◽

In Series ◽

Phosphate Buffered Saline

Abstract Background: Rodent mesenchymal stem/stromal cells (MSCs) enhance repair after ventilator-induced lung injury (VILI). We wished to determine the therapeutic potential of human MSCs (hMSCs) in repairing the rodent lung. Methods: In series 1, anesthetized rats underwent VILI (series 1A, n = 8 to 9 per group) or protective ventilation (series 1B, n = 4 per group). After VILI, they were randomized to intravenous administration of (1) vehicle (phosphate-buffered saline); (2) fibroblasts (1 × 107 cells/kg); or (3) human MSCs (1 × 107 cells/kg) and the effect on restoration of lung function and structure assessed. In series 2, the efficacy of hMSC doses of 1, 2, 5, and 10 million/kg was examined (n = 8 per group). Series 3 compared the efficacy of both intratracheal and intraperitoneal hMSC administration to intravascular delivery (n = 5–10 per group). Series 4 examined the efficacy of delayed hMSC administration (n = 8 per group). Results: Human MSC’s enhanced lung repair, restoring oxygenation (131 ± 19 vs. 103 ± 11 vs. 95 ± 11 mmHg, P = 0.004) compared to vehicle or fibroblast therapy, respectively. hMSCs improved lung compliance, reducing alveolar edema, and restoring lung architecture. hMSCs attenuated lung inflammation, decreasing alveolar cellular infiltration, and decreasing cytokine-induced neutrophil chemoattractant-1 and interleukin-6 while increasing keratinocyte growth factor concentrations. The lowest effective hMSC dose was 2 × 106 hMSC/kg. Intraperitoneal hMSC delivery was less effective than intratracheal or intravenous hMSC. hMSCs enhanced lung repair when administered at later time points after VILI. Conclusions: hMSC therapy demonstrates therapeutic potential in enhancing recovery after VILI.

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Oesophageal balloon positioning by echocardiography to guide positive pressure ventilation

Journal of Clinical Monitoring and Computing ◽

10.1007/s10877-021-00730-z ◽

2021 ◽

Author(s):

Marco Betello ◽

Raphael Giraud ◽

Karim Bendjelid

Keyword(s):

Lung Injury ◽

Respiratory System ◽

Positive Pressure Ventilation ◽

Respiratory Mechanics ◽

Lung Compliance ◽

Technical Note ◽

Positive Pressure ◽

Obese Patients ◽

Correct Position ◽

Ventilator Induced Lung Injury

AbstractUnderstanding the respiratory mechanics of ARDS patients is crucial to avoid ventilator-induced lung injury (VILI), and this is much more challenging if not only lung compliance is altered but the whole compliance of the respiratory system is abnormal, as in obese patients. We face this problem daily in the ICU, and to optimize ventilation, we estimate respiratory mechanics using an oesophageal balloon. The balloon position is crucial to assess reliable values. In the present technical note, we describe the use of echocardiography to confirm the correct position of this instrument.

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Effects of Intratracheal Mesenchymal Stromal Cell Therapy during Recovery and Resolution after Ventilator-induced Lung Injury

Anesthesiology ◽

10.1097/aln.0b013e318287ba08 ◽

2013 ◽

Vol 118 (4) ◽

pp. 924-932 ◽

Cited By ~ 68

Author(s):

Gerard F. Curley ◽

Bilal Ansari ◽

Mairead Hayes ◽

James Devaney ◽

Claire Masterson ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Enhanced Recovery ◽

Lung Compliance ◽

Lung Water ◽

Lung Repair ◽

Ventilator Induced Lung Injury ◽

Factor Α ◽

Phosphate Buffered Saline ◽

Ventilation Induced Lung Injury

Abstract Background: Mesenchymal stromal cells (MSCs) have been demonstrated to attenuate acute lung injury when delivered by intravenous or intratracheal routes. The authors aimed to determine the efficacy of and mechanism of action of intratracheal MSC therapy and to compare their efficacy in enhancing lung repair after ventilation-induced lung injury with intravenous MSC therapy. Methods: After induction of anesthesia, rats were orotracheally intubated and subjected to ventilation-induced lung injury (respiratory rate 18 min−1, Pinsp 35 cm H2O,) to produce severe lung injury. After recovery, animals were randomized to receive: (1) no therapy, n = 4; (2) intratracheal vehicle (phosphate-buffered saline, 300 µl, n = 8); (3) intratracheal fibroblasts (4 × 106 cells, n = 8); (4) intratracheal MSCs (4 × 106 cells, n = 8); (5) intratracheal conditioned medium (300 µl, n = 8); or (6) intravenous MSCs (4 × 106 cells, n = 4). The extent of recovery after acute lung injury and the inflammatory response was assessed after 48 h. Results: Intratracheal MSC therapy enhanced repair after ventilation-induced lung injury, improving arterial oxygenation (mean ± SD, 146 ± 3.9 vs. 110.8 ± 21.5 mmHg), restoring lung compliance (1.04 ± 0.11 vs. 0.83 ± 0.06 ml·cm H2O−1), reducing total lung water, and decreasing lung inflammation and histologic injury compared with control. Intratracheal MSC therapy attenuated alveolar tumor necrosis factor-α (130 ± 43 vs. 488 ± 211 pg·ml−1) and interleukin-6 concentrations (138 ± 18 vs. 260 ± 82 pg·ml−1). The efficacy of intratracheal MSCs was comparable with intravenous MSC therapy. Intratracheal MSCs seemed to act via a paracine mechanism, with conditioned MSC medium also enhancing lung repair after injury. Conclusions: Intratracheal MSC therapy enhanced recovery after ventilation-induced lung injury via a paracrine mechanism, and was as effective as intravenous MSC therapy.

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Volume-Guaranteed Ventilation

Neonatal Network The Journal of Neonatal Nursing ◽

10.1891/0730-0832.22.2.17 ◽

2003 ◽

Vol 22 (2) ◽

pp. 17-21 ◽

Cited By ~ 2

Author(s):

Cheryl Riley ◽

Jobeth Pilcher

Keyword(s):

Lung Injury ◽

Tidal Volume ◽

Lung Compliance ◽

Respiratory Drive ◽

Limited Time ◽

Careful Attention ◽

Primary Mode ◽

Ventilator Induced Lung Injury ◽

New Strategies ◽

Ventilator Settings

Pressure-limited, time-cycled ventilation has been the primary mode of ventilation for neonates for several decades. But the realization that volume rather than pressure causes ventilator-induced lung injury has led to the development of new strategies for ventilation. Volume guarantee is a mode of ventilation that automatically adjusts the inspiratory pressure to achieve a set tidal volume according to changes in lung compliance or resistance or the patient’s respiratory drive. Volume-guaranteed ventilation delivers a specific, preset volume of gas, and inspiration ends when it has been delivered. This mode of ventilation requires careful attention to the infant and to ventilator settings.

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