Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury

Rationale: Intratidal changes in regional lung aeration, as assessed with dynamic four-dimensional computed tomography (CT; 4DCT), may indicate the processes of recruitment and derecruitment, thus portending atelectrauma during mechanical ventilation. In this study, we characterized the time constants associated with deaeration during the expiratory phase of pressure-controlled ventilation in pigs before and after acute lung injury using respiratory-gated 4DCT and image registration.Methods: Eleven pigs were mechanically ventilated in pressure-controlled mode under baseline conditions and following an oleic acid model of acute lung injury. Dynamic 4DCT scans were acquired without interrupting ventilation. Automated segmentation of lung parenchyma was obtained by a convolutional neural network. Respiratory structures were aligned using 4D image registration. Exponential regression was performed on the time-varying CT density in each aligned voxel during exhalation, resulting in regional estimates of intratidal aeration change and deaeration time constants. Regressions were also performed for regional and total exhaled gas volume changes.Results: Normally and poorly aerated lung regions demonstrated the largest median intratidal aeration changes during exhalation, compared to minimal changes within hyper- and non-aerated regions. Following lung injury, median time constants throughout normally aerated regions within each subject were greater than respective values for poorly aerated regions. However, parametric response mapping revealed an association between larger intratidal aeration changes and slower time constants. Lower aeration and faster time constants were observed for the dependent lung regions in the supine position. Regional gas volume changes exhibited faster time constants compared to regional density time constants, as well as better correspondence to total exhaled volume time constants.Conclusion: Mechanical time constants based on exhaled gas volume underestimate regional aeration time constants. After lung injury, poorly aerated regions experience larger intratidal changes in aeration over shorter time scales compared to normally aerated regions. However, the largest intratidal aeration changes occur over the longest time scales within poorly aerated regions. These dynamic 4DCT imaging data provide supporting evidence for the susceptibility of poorly aerated regions to ventilator-induced lung injury, and for the functional benefits of short exhalation times during mechanical ventilation of injured lungs.

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Modeling kinetics of infused 13NN-saline in acute lung injury

Journal of Applied Physiology ◽

10.1152/japplphysiol.00401.2003 ◽

2003 ◽

Vol 95 (6) ◽

pp. 2471-2484 ◽

Cited By ~ 17

Author(s):

K. O'Neill ◽

J. G. Venegas ◽

T. Richter ◽

R. S. Harris ◽

J. D. H. Layfield ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Volume Of Distribution ◽

Model Fit ◽

Emission Tomography ◽

Central Venous ◽

Blood Concentrations ◽

Positron Emission ◽

Gas Volume ◽

Kinetics Of

A mathematical model was developed to estimate right-to-left shunt (Fs) and the volume of distribution of 13NN in alveolar gas (VA) and shunt tissue (Vs). The data obtained from this model are complementary to, and obtained simultaneously with, pulmonary functional positron emission tomography (PET). The model describes 13NN kinetics in four compartments: central mixing volume, gas-exchanging lung, shunting compartment, and systemic recirculation. To validate the model, five normal prone (NP) and six surfactant-depleted sheep in the supine (LS) and prone (LP) positions were studied under general anesthesia. A central venous bolus of 13NN-labeled saline was injected at the onset of apnea as PET imaging and arterial 13NN sampling were initiated. The model fit the tracer kinetics well (mean r2 = 0.93). Monte Carlo simulations showed that parameters could be accurately identified in the presence of expected experimental noise. Fs derived from the model correlated well with shunt estimates derived from O2 blood concentrations and from PET images. Fs was higher for LS (54 ± 18%) than for LP (5 ± 4%) and NP (1 ± 1%, P < 0.01). VA, as a fraction of PET-measured lung gas volume, was lower for LS (0.18 ± 0.09) than for LP (0.96 ± 0.28, P < 0.01), whereas Vs, as a fraction of PET-measured lung tissue volume, was higher for LS (0.46 ± 0.26) than for LP (0.05 ± 0.08, P < 0.01). The main conclusions are as follows: 1) the model accurately describes measured arterial 13NN kinetics and provides estimates of Fs, and 2) in this animal model of acute lung injury, the fraction of available gas volume participating in gas exchange is reduced in the supine position.

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Effect of CO2 on LPS-induced cytokine responses in rat alveolar macrophages

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00394.2004 ◽

2005 ◽

Vol 289 (1) ◽

pp. L96-L103 ◽

Cited By ~ 25

Author(s):

Carol J. Lang ◽

Ping Dong ◽

Emma K. Hosszu ◽

Ian R. Doyle

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Metabolic Activity ◽

Alveolar Macrophages ◽

Culture Media ◽

Cytokine Release ◽

Cytokine Responses ◽

Tnf Α ◽

Effects Of Ph ◽

The Media

Alveolar macrophages (AM) may be exposed to a range of CO2 and pH levels depending on their location in the alveoli and the health of the lung. Cytokines produced by AM contribute to inflammation in acute lung injury (ALI). Current ventilatory practices for the management of ALI favor low tidal volumes, which can give rise to increases in CO2 and changes in pH of the alveolar microenvironment. Here we examined the effect of CO2 on cytokine release from LPS-stimulated rat AM. AM were incubated for 1–4 h under different atmospheric gas mixtures ranging from 2.5–20% CO2. To distinguish between effects of pH and CO2, the culture media were also buffered to pH 7.2 with NaHCO3. Cell metabolic activity, but not cell viability, decreased and increased significantly after 4 h at 20 and 2.5% CO2, respectively. Increasing CO2 decreased TNF-α secretion but had no effect on lysate TNF-α. Buffering the media abated the effects of CO2 on TNF-α secretion. CO2 increased cytokine-induced neutrophil chemoattractant factor-1 secretion only when the pH was buffered to 7.2. Effects of CO2 on cytokine responses were reversible. In conclusion, the effects of CO2 on cytokine lysate levels and/or secretion in AM are cytokine specific and, depending on both the cytokine and the immediate microenvironment, may be beneficial or detrimental to ALI.

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