Targeted Versus Continuous Delivery of Volatile Anesthetics During Cholinergic Bronchoconstriction

Mondoñedo, Jarred R.; McNeil, John S.; Herrmann, Jacob; Simon, Brett A.; Kaczka, David W.

doi:10.1115/1.4040001

Cited by 4 publications

(3 citation statements)

References 68 publications

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“…Measurement of the difference between airway opening and esophageal pressures (P es ) as a surrogate of transpulmonary pressure offers the possibility to separate the mechanical properties of these two compartments. This approach has been successfully applied to humans (7, 10 -12, 14, 29), dogs (5,20,27), cats (17), rabbits (1,16), and rats (22,24,31). However, no such measurements have been performed in mice despite the rapidly increasing importance of this animal model in a wide variety of respiratory diseases.…”

Section: Introductionmentioning

confidence: 99%

Different contributions from lungs and chest wall to respiratory mechanics in mice, rats, and rabbits

Südy

Fodor

Rocha

et al. 2019

Journal of Applied Physiology

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Changes in lung mechanics are frequently inferred from intact-chest measures of total respiratory system mechanics without consideration of the chest wall contribution. The participation of lungs and chest wall in respiratory mechanics has not been evaluated systematically in small animals commonly used in respiratory research. Thus, we compared these contributions in intact-chest mice, rats, and rabbits and further characterized the influence of positive end-expiratory pressure (PEEP). Forced oscillation technique was applied to anesthetized mechanically ventilated healthy animals to obtain total respiratory system impedance (Zrs) at 0, 3, and 6 cmH2O PEEP levels. Esophageal pressure was measured by a catheter-tip micromanometer to separate Zrs into pulmonary (ZL) and chest wall (Zcw) components. A model containing a frequency-independent Newtonian resistance (RN), inertance, and a constant-phase tissue damping (G) and elastance (H) was fitted to Zrs, ZL, and Zcw spectra. The contribution of Zcw to RN was negligible in all species and PEEP levels studied. However, the participation of Zcw in G and H was significant in all species and increased significantly with increasing PEEP and animal size (rabbit > rat > mice). Even in mice, the chest wall contribution to G and H was still considerable, reaching 47.0 ± 4.0(SE)% and 32.9 ± 5.9% for G and H, respectively. These findings demonstrate that airway parameters can be assessed from respiratory system mechanical measurements. However, the contribution from the chest wall should be considered when intact-chest measurements are used to estimate lung parenchymal mechanics in small laboratory models (even in mice), particularly at elevated PEEP levels. NEW & NOTEWORTHY In species commonly used in respiratory research (rabbits, rats, mice), esophageal pressure-based estimates revealed negligible contribution from the chest wall to the Newtonian resistance. Conversely, chest wall participation in the viscoelastic tissue mechanical parameters increased with body size (rabbit > rat > mice) and positive end-expiratory pressure, with contribution varying between 30 and 50%, even in mice. These findings demonstrate the potential biasing effects of the chest wall when lung tissue mechanics are inferred from intact-chest measurements in small laboratory animals.

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Section: Introductionmentioning

confidence: 99%

Different contributions from lungs and chest wall to respiratory mechanics in mice, rats, and rabbits

Südy

Fodor

Rocha

et al. 2019

Journal of Applied Physiology

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“…As VDF reflects the amount of gas in the conducting airways [ 20 ], this finding demonstrates that there was no change in the anatomical dead space fraction following either intervention. While severe bronchoconstriction in the hypocapnic left lung may yield a unilateral reduction in apparent anatomic dead space [ 35 ], the redistribution of tidal volume to the right lung may have overinflated this compartment, thereby counterbalancing the anatomic dead space.…”

Section: Discussionmentioning

confidence: 99%

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats

Tolnai,

Ballók,

Südy

et al. 2024

BMC Pulm Med

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Background Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism. Methods Anesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography. Results In the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting. Conclusions Our findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

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“… 5 Given such factors, aerosolized therapeutic agents may be deposited within the upper airway and tracheobronchial tree, where they can be systemically absorbed. 6 …”

Section: Introductionmentioning

confidence: 99%

Positron Emission Tomography-Computed Tomography Imaging of Selective Lobar Delivery of Stem Cells in Ex Vivo Lung Model of Mechanical Ventilation

Maracaja

Khanna

Murphy

et al. 2023

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Introduction: The delivery of cell therapies may be an important frontier to treat different respiratory diseases in the near future. However, the cell size, delivery conditions, cell viability, and effect in the pulmonary function are critical factors. We performed a proof-of-concept experiment using ex vivo lungs and novel subglottic airway device that allows for selective lobar isolation and administration of drugs and biologics in liquid solution deep into the lung tissues, while simultaneously ventilating the rest of the lung lobes. Methods: We used radiolabeled cells and positron emission tomography-computed tomography (PET-CT) imaging to demonstrate the feasibility of high-yield cell delivery to a specifically targeted lobe. This study proposes an alternative delivery method of live cells labeled with radioactive isotope into the lung parenchyma and tracks the cell delivery using PET-CT imaging. The technique combines selective lobar isolation and lobar infusion to carry large particles distal to the trachea, subtending bronchial segments and reaching alveoli in targeted regions. Results: The solution with cells and carrier achieved a complete and homogeneous lobar distribution. An increase in tissue density was shown on the computed tomography (CT) scan, and the PET-CT imaging demonstrated retention of the activity at central, peripheral lung parenchyma, and pleural surface. The increase in CT density and metabolic activity of the isotope was restricted to the desired lobe only without leak to other lobes. Conclusion: The selective lobe delivery is targeted and imaging-guided by bronchoscopy and CT to a specific diseased lobe during mechanical ventilation. The feasibility of high-yield cell delivery demonstrated in this study will lead to the development of potential novel therapies that contribute to lung health.

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Targeted Versus Continuous Delivery of Volatile Anesthetics During Cholinergic Bronchoconstriction

Cited by 4 publications

References 68 publications

Different contributions from lungs and chest wall to respiratory mechanics in mice, rats, and rabbits

Different contributions from lungs and chest wall to respiratory mechanics in mice, rats, and rabbits

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats

Positron Emission Tomography-Computed Tomography Imaging of Selective Lobar Delivery of Stem Cells in Ex Vivo Lung Model of Mechanical Ventilation

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