scholarly journals In vitro validation and characterization of pulsed inhaled nitric oxide administration during early inspiration

2021 ◽  
Author(s):  
Philipp A. Pickerodt ◽  
Moritz B. T. Hofferberth ◽  
Thilo Busch ◽  
Martin Russ ◽  
Mahdi Taher ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mechanical Ventilation ◽  
Lung Model ◽  
Inspiratory Time ◽  
Inspiratory Phase ◽  
Inspiratory Limb ◽  
Pulsed Injection ◽  
Ventilator Settings

Abstract Purpose Admixture of nitric oxide (NO) to the gas inspired with mechanical ventilation can be achieved through continuous, timed, or pulsed injection of NO into the inspiratory limb. The dose and timing of NO injection govern the inspired and intrapulmonary effect site concentrations achieved with different administration modes. Here we test the effectiveness and target reliability of a new mode injecting pulsed NO boluses exclusively during early inspiration. Methods An in vitro lung model was operated under various ventilator settings. Admixture of NO through injection into the inspiratory limb was timed either (i) selectively during early inspiration (“pulsed delivery”), or as customary, (ii) during inspiratory time or (iii) the entire respiratory cycle. Set NO target concentrations of 5–40 parts per million (ppm) were tested for agreement with the yield NO concentrations measured at various sites in the inspiratory limb, to assess the effectiveness of these NO administration modes. Results Pulsed delivery produced inspiratory NO concentrations comparable with those of customary modes of NO administration. At low (450 ml) and ultra-low (230 ml) tidal volumes, pulsed delivery yielded better agreement of the set target (up to 40 ppm) and inspiratory NO concentrations as compared to customary modes. Pulsed delivery with NO injection close to the artificial lung yielded higher intrapulmonary NO concentrations than with NO injection close to the ventilator. The maximum inspiratory NO concentration observed in the trachea (68 ± 30 ppm) occurred with pulsed delivery at a set target of 40 ppm. Conclusion Pulsed early inspiratory phase NO injection is as effective as continuous or non-selective admixture of NO to inspired gas and may confer improved target reliability, especially at low, lung protective tidal volumes.

Inaccuracies of Nitric Oxide Delivery Systems during Adult Mechanical Ventilation

1997 ◽  
Vol 86 (3) ◽  
pp. 676-688 ◽  
Author(s):  
Hideaki Imanaka ◽  
Dean Hess ◽  
Max Kirmse ◽  
Luca M. Bigatello ◽  
Robert M. Kacmarek ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mechanical Ventilation ◽  
Pressure Control ◽  
Delivery Systems ◽  
Control Ventilation ◽  
Lung Model ◽  
Pressure Control Ventilation ◽  
Ventilator Circuit ◽  
Slow Response ◽  
Inspiratory Limb

Background Various systems to administer inhaled nitric oxide (NO) have been used in patients and experimental animals. We used a lung model to evaluate five NO delivery systems during mechanical ventilation with various ventilatory patterns. Methods An adult mechanical ventilator was attached to a test lung configured to separate inspired and expired gases. Four injection systems were evaluated with NO injected either into the inspiratory circuit 90 cm proximal to the Y piece or directly at the Y piece and delivered either continuously or only during the inspiratory phase. Alternatively, NO was mixed with air using a blender and delivered to the high-pressure air inlet of the ventilator. Nitric oxide concentration was measured from the inspiratory limb of the ventilator circuit and the tracheal level using rapid- and slow-response chemiluminescence analyzers. The ventilator was set for constant-flow volume control ventilation, pressure control ventilation, pressure support ventilation, or synchronized intermittent mandatory ventilation. Tidal volumes of 0.5 l and 1 l were evaluated with inspiratory times of 1 s and 2 s. Results The system that premixed NO proximal to the ventilator was the only one that maintained constant NO delivery regardless of ventilatory pattern. The other systems delivered variable NO concentration during pressure control ventilation and spontaneous breathing modes. Systems that injected a continuous flow of NO delivered peak NO concentrations greater than the calculated dose. These variations were not apparent when a slow-response chemiluminescence analyzer was used. Conclusions NO delivery systems that inject NO at a constant rate, either continuously or during inspiration only, into the inspiratory limb of the ventilator circuit produce highly variable and unpredictable NO delivery when inspiratory flow is not constant. Such systems may deliver a very high NO concentration to the lungs, which is not accurately reflected by measurements performed with slow-response analyzers.

scholarly journals A novel long intergenic non-coding RNA, Nostrill, regulates iNOS gene transcription and neurotoxicity in microglia

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Nicholas W. Mathy ◽  
Olivia Burleigh ◽  
Andrew Kochvar ◽  
Erin R. Whiteford ◽  
Matthew Behrens ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
No Production ◽  
Cortical Tissue ◽  
Non Coding Rna ◽  
Transcriptional Regulatory ◽  
Lncrna Locus ◽  
Rna Immunoprecipitation ◽  
Long Non Coding Rna

Abstract Background Microglia are resident immunocompetent and phagocytic cells in the CNS. Pro-inflammatory microglia, stimulated by microbial signals such as bacterial lipopolysaccharide (LPS), viral RNAs, or inflammatory cytokines, are neurotoxic and associated with pathogenesis of several neurodegenerative diseases. Long non-coding RNAs (lncRNA) are emerging as important tissue-specific regulatory molecules directing cell differentiation and functional states and may help direct proinflammatory responses of microglia. Characterization of lncRNAs upregulated in proinflammatory microglia, such as NR_126553 or 2500002B13Rik, now termed Nostrill (iNOS Transcriptional Regulatory Intergenic LncRNA Locus) increases our understanding of molecular mechanisms in CNS innate immunity. Methods Microglial gene expression array analyses and qRT-PCR were used to identify a novel long intergenic non-coding RNA, Nostrill, upregulated in LPS-stimulated microglial cell lines, LPS-stimulated primary microglia, and LPS-injected mouse cortical tissue. Silencing and overexpression studies, RNA immunoprecipitation, chromatin immunoprecipitation, chromatin isolation by RNA purification assays, and qRT-PCR were used to study the function of this long non-coding RNA in microglia. In vitro assays were used to examine the effects of silencing the novel long non-coding RNA in LPS-stimulated microglia on neurotoxicity. Results We report here characterization of intergenic lncRNA, NR_126553, or 2500002B13Rik now termed Nostrill (iNOS Transcriptional Regulatory Intergenic LncRNA Locus). Nostrill is induced by LPS stimulation in BV2 cells, primary murine microglia, and in cortical tissue of LPS-injected mice. Induction of Nostrill is NF-κB dependent and silencing of Nostrill decreased inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in BV2 and primary microglial cells. Overexpression of Nostrill increased iNOS expression and NO production. RNA immunoprecipitation assays demonstrated that Nostrill is physically associated with NF-κB subunit p65 following LPS stimulation. Silencing of Nostrill significantly reduced NF-κB p65 and RNA polymerase II recruitment to the iNOS promoter and decreased H3K4me3 activating histone modifications at iNOS gene loci. In vitro studies demonstrated that silencing of Nostrill in microglia reduced LPS-stimulated microglial neurotoxicity. Conclusions Our data indicate a new regulatory role of the NF-κB-induced Nostrill and suggest that Nostrill acts as a co-activator of transcription of iNOS resulting in the production of nitric oxide by microglia through modulation of epigenetic chromatin remodeling. Nostrill may be a target for reducing the neurotoxicity associated with iNOS-mediated inflammatory processes in microglia during neurodegeneration.

Aerosol Delivery During Mechanical Ventilation: A Predictive In-Vitro Lung Model

1992 ◽  
Vol 5 (4) ◽  
pp. 251-259 ◽  
Author(s):  
H.D. FULLER ◽  
M.B. DOLOVICH ◽  
C. CHAMBERS ◽  
M.T. NEWHOUSE
Keyword(s):  
Mechanical Ventilation ◽  
Lung Model ◽  
Aerosol Delivery

scholarly journals Accurate Measurement of Functional Residual Capacity and Oxygen Consumption of Patients on Mechanical Ventilation

1983 ◽  
Vol 11 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Kevin R. Cooper ◽  
Peter A. Boswell
Keyword(s):  
Intensive Care Unit ◽  
Mechanical Ventilation ◽  
Intensive Care ◽  
Oxygen Consumption ◽  
Functional Residual Capacity ◽  
Lung Model ◽  
Capacity Measurement ◽  
Icu Patients ◽  
Residual Capacity

We developed an apparatus and technique for the simultaneous measurement of functional residual capacity and oxygen uptake (V̇O2) for use in intensive care unit (ICU) patients. The accuracy of the functional residual capacity measurement was proven using an in vitro lung model and the reproducibility of this measurement was established by use in ICU patients. We tested the accuracy of the V̇O2 measurement in comparison with two other methods in common use among ICU patients and our method proved accurate. We conclude that this technique for measurement of functional residual capacity and V̇O2 is highly accurate and easily applied to patients on any mode of mechanical ventilation.

scholarly journals Characterization of Alanine Catabolism in Pseudomonas aeruginosa and Its Importance for Proliferation In Vivo

2009 ◽  
Vol 191 (20) ◽  
pp. 6329-6334 ◽  
Author(s):  
Megan L. Boulette ◽  
Patricia J. Baynham ◽  
Peter A. Jorth ◽  
Irena Kukavica-Ibrulj ◽  
Aissa Longoria ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Carbon Sources ◽  
Opportunistic Pathogen ◽  
Lung Model ◽  
Host Infection ◽  
In Vivo Growth

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa causes a variety of infections in immunocompromised individuals, including individuals with the heritable disease cystic fibrosis. Like the carbon sources metabolized by many disease-causing bacteria, the carbon sources metabolized by P. aeruginosa at the host infection site are unknown. We recently reported that l-alanine is a preferred carbon source for P. aeruginosa and that two genes potentially involved in alanine catabolism (dadA and dadX) are induced during in vivo growth in the rat peritoneum and during in vitro growth in sputum (mucus) collected from the lungs of individuals with cystic fibrosis. The goals of this study were to characterize factors required for alanine catabolism in P. aeruginosa and to assess the importance of these factors for in vivo growth. Our results reveal that dadA and dadX are arranged in an operon and are required for catabolism of l-alanine. The dad operon is inducible by l-alanine, d-alanine, and l-valine, and induction is dependent on the transcriptional regulator Lrp. Finally, we show that a mutant unable to catabolize dl-alanine displays decreased competitiveness in a rat lung model of infection.

Delivery of a Nebulized Aerosol to a Lung Model during Mechanical Ventilation: Effect of Ventilator Settings and Nebulizer Type, Position, and Volume of Fill

1992 ◽  
Vol 146 (2) ◽  
pp. 383-388 ◽  
Author(s):  
Michael J. O'doherty ◽  
Simon H. L. Thomas ◽  
Christopher J. Page ◽  
David F. Treacher ◽  
Thomas O. Nunan
Keyword(s):  
Mechanical Ventilation ◽  
Lung Model ◽  
Ventilator Settings

scholarly journals Delivered dose with jet and mesh nebulisers during spontaneous breathing, noninvasive ventilation, and mechanical ventilation using adult lung models

2021 ◽  
pp. 00027-2021
Author(s):  
Arzu Ari ◽  
James B. Fink
Keyword(s):  
Drug Delivery ◽  
Mechanical Ventilation ◽  
Noninvasive Ventilation ◽  
Spontaneous Breathing ◽  
Lung Model ◽  
Heated Humidifier ◽  
Test Lung ◽  
Adult Lung ◽  
Inspiratory Limb ◽  
Delivered Dose

What is the delivered dose with jet (JN) and mesh nebulizers (MN) during spontaneous breathing (SB), noninvasive ventilation (NIV), and mechanical ventilation (MV) using an adult lung model with exhaled humidity (EH)? Albuterol sulfate (2.5 mg·3 mL−1) delivery with JN (Mistymax10) and MN (AerogenSolo) was compared during SB, NIV, and MV using breathing parameters (Vt=450 mL, RR=20 bpm, I:E=1:3) with three lung models simulating EH. A manikin was attached to a sinusoidal pump via a filter at the bronchi to simulate an adult with SB. A ventilator (V60) was attached via a facemask to a manikin with a filter at the bronchi connected to a test lung to simulate an adult receiving NIV. A ventilator-dependent adult was simulated through a ventilator (Servo i) operated with a heated humidifier (Fisher&Paykel) attached to an ETT with a heated-wire circuit. The ETT was inserted into a filter (RespirgardII). A heated humidifier was placed between the filter and test lung to simulate EH (35±2° C, 100% RH). Nebulizers were placed at the Y-piece of the inspiratory limb during MV and positioned between the facemask and the leak-port during NIV. A mouthpiece was used during SB. The delivered dose was collected in an absolute filter that was attached to the bronchi of the mannequin during each aerosol treatment and measured with spectrohoptometry. Drug delivery during MV was significantly greater than NIV and SB with MN (p=0.0001) but not with JN (p=0.384). Delivery efficiency of MN was greater than JN during MV (p=0.0001), NIV (p=0.0001), and SB (p=0.0001). Drug delivery with MN was greater and differed between MV, NIV, and SB, while deposition was low with JN and similar between the modes of ventilation tested.

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