Design of a new variable-ventilation method optimized for lung recruitment in mice

Variable ventilation (VV), characterized by breath-to-breath variation of tidal volume (Vt) and breathing rate (f), has been shown to improve lung mechanics and blood oxygenation during acute lung injury in many species compared with conventional ventilation (CV), characterized by constant Vt and f. During CV as well as VV, the lungs of mice tend to collapse over time; therefore, the goal of this study was to develop a new VV mode (VVN) with an optimized distribution of Vt to maximize recruitment. Groups of normal and HCl-injured mice were subjected to 1 h of CV, original VV (VVO), CV with periodic large breaths (CVLB), and VVN, and the effects of ventilation modes on respiratory mechanics, airway pressure, blood oxygenation, and IL-1β were assessed. During CV and VVO, normal and injured mice showed regional lung collapse with increased airway pressures and poor oxygenation. CVLB and VVN resulted in a stable dynamic equilibrium with significantly improved respiratory mechanics and oxygenation. Nevertheless, VVN provided a consistently better physiological response. In injured mice, VVO and VVN, but not CVLB, were able to reduce the IL-1β-related inflammatory response compared with CV. In conclusion, our results suggest that application of higher Vt values than the single Vt currently used in clinical situations helps stabilize lung function. In addition, variable stretch patterns delivered to the lung by VV can reduce the progression of lung injury due to ventilation in injured mice.

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Variable ventilation induces endogenous surfactant release in normal guinea pigs

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00036.2003 ◽

2003 ◽

Vol 285 (2) ◽

pp. L370-L375 ◽

Cited By ~ 63

Author(s):

Stephen P. Arold ◽

Béla Suki ◽

Adriano M. Alencar ◽

Kenneth R. Lutchen ◽

Edward P. Ingenito

Keyword(s):

Mechanical Ventilation ◽

Lung Injury ◽

Protein Content ◽

Guinea Pigs ◽

Lung Lavage ◽

Blood Oxygenation ◽

Lung Mechanics ◽

Control Group ◽

Whole Lung Lavage ◽

Variable Ventilation

Variable or noisy ventilation, which includes random breath-to-breath variations in tidal volume (Vt) and frequency, has been shown to consistently improve blood oxygenation during mechanical ventilation in various models of acute lung injury. To further understand the effects of variable ventilation on lung physiology and biology, we mechanically ventilated 11 normal guinea pigs for 3 h using constant-Vt ventilation ( n = 6) or variable ventilation ( n = 5). After 3 h of ventilation, each animal underwent whole lung lavage for determination of alveolar surfactant content and composition, while protein content was assayed as a possible marker of injury. Another group of animals underwent whole lung lavage in the absence of mechanical ventilation to serve as an unventilated control group ( n = 5). Although lung mechanics did not vary significantly between groups, we found that variable ventilation improved oxygenation, increased surfactant levels nearly twofold, and attenuated alveolar protein content compared with animals ventilated with constant Vt. These data demonstrate that random variations in Vt promote endogenous release of biochemically intact surfactant, which improves alveolar stability, apparently reducing lung injury.

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Effect of pressure-controlled ventilation-volume guaranteed mode combined with individualized positive end-expiratory pressure on respiratory mechanics, oxygenation and lung injury in patients undergoing laparoscopic surgery in Trendelenburg position

Journal of Clinical Monitoring and Computing ◽

10.1007/s10877-021-00750-9 ◽

2021 ◽

Author(s):

Jianli Li ◽

Saixian Ma ◽

Xiujie Chang ◽

Songxu Ju ◽

Meng Zhang ◽

...

Keyword(s):

Laparoscopic Surgery ◽

Lung Injury ◽

Respiratory Mechanics ◽

Lung Mechanics ◽

Trial Registry ◽

Positive End Expiratory Pressure ◽

Clinical Trial Registry ◽

Trendelenburg Position ◽

Pressure Controlled Ventilation ◽

Pressure Controlled

AbstractThe study aimed to investigate the efficacy of PCV-VG combined with individual PEEP during laparoscopic surgery in the Trendelenburg position. 120 patients were randomly divided into four groups: VF group (VCV plus 5cmH2O PEEP), PF group (PCV-VG plus 5cmH2O PEEP), VI group (VCV plus individual PEEP), and PI group (PCV-VG plus individual PEEP). Pmean, Ppeak, Cdyn, PaO2/FiO2, VD/VT, A-aDO2 and Qs/Qt were recorded at T1 (15 min after the induction of anesthesia), T2 (60 min after pneumoperitoneum), and T3 (5 min at the end of anesthesia). The CC16 and IL-6 were measured at T1 and T3. Our results showed that the Pmean was increased in VI and PI group, and the Ppeak was lower in PI group at T2. At T2 and T3, the Cdyn of PI group was higher than that in other groups, and PaO2/FiO2 was increased in PI group compared with VF and VI group. At T2 and T3, A-aDO2 of PI and PF group was reduced than that in other groups. The Qs/Qt was decreased in PI group compared with VF and VI group at T2 and T3. At T2, VD/VT in PI group was decreased than other groups. At T3, the concentration of CC16 in PI group was lower compared with other groups, and IL-6 level of PI group was decreased than that in VF and VI group. In conclusion, the patients who underwent laparoscopic surgery, PCV-VG combined with individual PEEP produced favorable lung mechanics and oxygenation, and thus reducing inflammatory response and lung injury.Clinical Trial registry: chictr.org. identifier: ChiCTR-2100044928

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Chronic lung injury and impaired pulmonary function in a mouse model of acid ceramidase deficiency

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00223.2017 ◽

2018 ◽

Vol 314 (3) ◽

pp. L406-L420 ◽

Cited By ~ 12

Author(s):

Fabian P. S. Yu ◽

Diana Islam ◽

Jakub Sikora ◽

Shaalee Dworski ◽

Jiří Gurka ◽

...

Keyword(s):

Lung Function ◽

Lung Injury ◽

Mouse Model ◽

Vascular Permeability ◽

Phospholipid Composition ◽

Blood Oxygenation ◽

Lung Mechanics ◽

Neurological Involvement ◽

Lysosomal Storage ◽

Acid Ceramidase

Farber disease (FD) is a debilitating lysosomal storage disorder (LSD) caused by a deficiency of acid ceramidase (ACDase) activity due to mutations in the gene ASAH1. Patients with ACDase deficiency may develop a spectrum of clinical phenotypes. Severe cases of FD are frequently associated with neurological involvement, failure to thrive, and respiratory complications. Mice homozygous ( Asah1P361R/P361R) for an orthologous patient mutation in Asah1 recapitulate human FD. In this study, we show significant impairment in lung function, including low compliance and increased airway resistance in a mouse model of ACDase deficiency. Impaired lung mechanics in Farber mice resulted in decreased blood oxygenation and increased red blood cell production. Inflammatory cells were recruited to both perivascular and peribronchial areas of the lung. We observed large vacuolated foamy histiocytes that were full of storage material. An increase in vascular permeability led to protein leakage, edema, and impacted surfactant homeostasis in the lungs of Asah1P361R/P361R mice. Bronchial alveolar lavage fluid (BALF) extraction and analysis revealed accumulation of a highly turbid lipoprotein-like substance that was composed in part of surfactants, phospholipids, and ceramides. The phospholipid composition of BALF from Asah1P361R/P361R mice was severely altered, with an increase in both phosphatidylethanolamine (PE) and sphingomyelin (SM). Ceramides were also found at significantly higher levels in both BALF and lung tissue from Asah1P361R/P361R mice when compared with levels from wild-type animals. We demonstrate that a deficiency in ACDase leads to sphingolipid and phospholipid imbalance, chronic lung injury caused by significant inflammation, and increased vascular permeability, leading to impaired lung function.

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Biologically Variable Ventilation Improves Oxygenation and Respiratory Mechanics during One-lung Ventilation

Anesthesiology ◽

10.1097/00000542-200607000-00017 ◽

2006 ◽

Vol 105 (1) ◽

pp. 91-97 ◽

Cited By ~ 26

Author(s):

Michael C. McMullen ◽

Linda G. Girling ◽

M Ruth Graham ◽

W Alan C. Mutch

Keyword(s):

Tidal Volume ◽

Respiratory Mechanics ◽

Lung Ventilation ◽

Group Effect ◽

Shunt Fraction ◽

Static Compliance ◽

One Lung Ventilation ◽

Time Interaction ◽

Variable Ventilation ◽

Dead Space Ventilation

Background Hypoxemia is common during one-lung ventilation (OLV). Atelectasis contributes to the problem. Biologically variable ventilation (BVV), using microprocessors to reinstitute physiologic variability to respiratory rate and tidal volume, has been shown to be advantageous over conventional monotonous control mode ventilation (CMV) in improving oxygenation during the period of lung reinflation after OLV in an experimental model. Here, using a porcine model, the authors compared BVV with CMV during OLV to assess gas exchange and respiratory mechanics. Methods Eight pigs (25-30 kg) were studied in each of two groups. After induction of anesthesia-tidal volume 12 ml/kg with CMV and surgical intervention-tidal volume was reduced to 9 ml/kg. OLV was initiated with an endobronchial blocker, and the animals were randomly allocated to either continue CMV or switch to BVV for 90 min. After OLV, a recruitment maneuver was undertaken, and both lungs were ventilated for a further 60 min. At predetermined intervals, hemodynamics, respiratory gases (arterial, venous, and end-tidal samples) and mechanics (airway pressures, static and dynamic compliances) were measured. Derived indices (pulmonary vascular resistance, shunt fraction, and dead space ventilation) were calculated. Results By 15 min of OLV, arterial oxygen tension was greater in the BVV group (group x time interaction, P = 0.003), and shunt fraction was lower with BVV from 30 to 90 min (group effect, P = 0.0004). From 60 to 90 min, arterial carbon dioxide tension was lower with BVV (group x time interaction, P = 0.0001) and dead space ventilation was less from 60 to 90 min (group x time interaction, P = 0.0001). Static compliance was greater by 60 min of BVV and remained greater during return to ventilation of both lungs (group effect, P = 0.0001). Conclusions In this model of OLV, BVV resulted in superior gas exchange and respiratory mechanics when compared with CMV. Improved static compliance persisted with restoration of two-lung ventilation.

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Reversal of dependent lung collapse predicts response to lung recruitment in children with early acute lung injury

Pediatric Critical Care Medicine ◽

10.1097/pcc.0b013e318245579c ◽

2012 ◽

Vol 13 (5) ◽

pp. 509-515 ◽

Cited By ~ 23

Author(s):

Gerhard K. Wolf ◽

Camille Gómez-Laberge ◽

John N. Kheir ◽

David Zurakowski ◽

Brian K. Walsh ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Lung Recruitment ◽

Dependent Lung ◽

Lung Collapse

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Lung mechanics are both dose and tidal volume dependant in LPS-induced lung injury

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2009.06.008 ◽

2009 ◽

Vol 167 (3) ◽

pp. 333-340 ◽

Cited By ~ 18

Author(s):

Dani-Louise Dixon ◽

Hilde R. De Smet ◽

Andrew D. Bersten

Keyword(s):

Lung Injury ◽

Tidal Volume ◽

Lung Mechanics

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Lung Mechanics in Type L CoVID-19 Pneumonia: A Pseudo-Normal ARDS.

10.21203/rs.3.rs-78234/v1 ◽

2020 ◽

Author(s):

Lorenzo Viola ◽

Emanuele Russo ◽

Marco Benni ◽

Emiliano Gamberini ◽

Alessandro Circelli ◽

...

Keyword(s):

Mechanical Properties ◽

Respiratory System ◽

Respiratory Mechanics ◽

Blood Gases ◽

Lung Mechanics ◽

Prone Positioning ◽

Arterial Blood Gases ◽

Arterial Blood ◽

Esophageal Balloon ◽

Early Phases

Abstract Background. This study was conceived to provide systematic data about lung mechanics during early phases of CoVID-19 pneumonia, as long as to explore its variations during prone positioning. Methods. We enrolled four patients hospitalized in the Intensive Care Unit of “M. Bufalini” hospital, Cesena (Italy); after the positioning of an esophageal balloon, we measured mechanical power, respiratory system and transpulmonary parameters and arterial blood gases every 6 hours, just before decubitus change and 1 hour after prono-supination. Results. Both respiratory system and transpulmonary compliance and driving pressure confirmed the pseudo-normal respiratory mechanics of early CoVID-19 pneumonia (respectively, CRS 40.8 ml/cmH2O and DPRS 9.7 cmH2O; CL 53.1 ml/cmH2O and DPL 7.9 cmH2O). Interestingly, prone positioning involved a worsening in respiratory mechanical properties (CRS,SUP 56.3 ml/cmH2O and CRS,PR 41.5 ml/cmH2O – P 0.37; CL,SUP 80.8 ml/cmH2O and CL,PR 53.2 ml/cmH2O – P 0.23). Conclusions. Despite the severe ARDS pattern, respiratory system and lung mechanical properties during CoVID-19 pneumonia are pseudo-normal and tend to worsen during pronation. Trial registration. Restrospectively registered.

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Magnetic resonance imaging provides sensitive in vivo assessment of experimental ventilator-induced lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00459.2015 ◽

2016 ◽

Vol 311 (2) ◽

pp. L208-L218 ◽

Cited By ~ 8

Author(s):

Dean O. Kuethe ◽

Piotr T. Filipczak ◽

Jeremy M. Hix ◽

Andrew P. Gigliotti ◽

Raúl San José Estépar ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Lung Injury ◽

Real Time ◽

Critical Role ◽

Lung Mechanics ◽

Therapeutic Effects ◽

Resonance Imaging ◽

Ventilator Induced Lung Injury

Animal models play a critical role in the study of acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). One limitation has been the lack of a suitable method for serial assessment of acute lung injury (ALI) in vivo. In this study, we demonstrate the sensitivity of magnetic resonance imaging (MRI) to assess ALI in real time in rat models of VILI. Sprague-Dawley rats were untreated or treated with intratracheal lipopolysaccharide or PBS. After 48 h, animals were mechanically ventilated for up to 15 h to induce VILI. Free induction decay (FID)-projection images were made hourly. Image data were collected continuously for 30 min and divided into 13 phases of the ventilatory cycle to make cinematic images. Interleaved measurements of respiratory mechanics were performed using a flexiVent ventilator. The degree of lung infiltration was quantified in serial images throughout the progression or resolution of VILI. MRI detected VILI significantly earlier (3.8 ± 1.6 h) than it was detected by altered lung mechanics (9.5 ± 3.9 h, P = 0.0156). Animals with VILI had a significant increase in the Index of Infiltration ( P = 0.0027), and early regional lung infiltrates detected by MRI correlated with edema and inflammatory lung injury on histopathology. We were also able to visualize and quantify regression of VILI in real time upon institution of protective mechanical ventilation. Magnetic resonance lung imaging can be utilized to investigate mechanisms underlying the development and propagation of ALI, and to test the therapeutic effects of new treatments and ventilator strategies on the resolution of ALI.

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