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- Kaminsky, DA, et al.
(författare)
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Oscillation mechanics of the human lung periphery in asthma
- 2004
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 97:5, s. 1849-1858
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Tidskriftsartikel (refereegranskat)abstract
- To more precisely measure the mechanical properties of the lung periphery in asthma, we have developed a forced oscillation technique that applies a broad-band flow signal through a wedged bronchoscope. We interpreted the data from four healthy and eight mildly asthmatic subjects in terms of an anatomically accurate computer model of the wedged segment. There was substantial overlap in impedance between the two groups, with resistance ( R) showing minimal frequency dependence and elastance (E) showing positive and negative frequency dependence across subjects. After direct instillation of methacholine, R rose in both groups, but compared with healthy subjects, the asthmatic subjects displayed upward, parallel shifts in their dose-response curves. The baseline frequency-response patterns of E were enhanced after methacholine. Frequency dependencies of R and E were well reproduced in two normal subjects by a computational model that employed rigid airways connected to constant-phase tissue units but were better reproduced in the other two normal and three asthmatic subjects when the model employed heterogeneous, peripheral airway narrowing and compliant airways. To capture the frequency dependencies of R and E in the remaining five asthmatic subjects, the model was modified by increasing airway wall stiffness. These results indicate that the lung periphery of mildly asthmatic subjects is not well distinguished from that of healthy subjects by measurement of mechanical impedance at baseline, but group differences are seen after challenge with methacholine. Modeling of the response suggests that variable contributions of airway narrowing and wall compliance are operative in determining overall mechanical impedance of the lung periphery in humans with asthma, likely reflecting the functional consequences of airway inflammation and remodeling.
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- Lundblad, Lennart, et al.
(författare)
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A reevaluation of the validity of unrestrained plethysmography in mice
- 2002
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 93:4, s. 1198-1207
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Tidskriftsartikel (refereegranskat)abstract
- Presently, unrestrained plethysmography is widely used to assess bronchial responsiveness in mice. An empirical quantity known as enhanced pause is derived from the plethysmographic box pressure [P-b( t), where t is time] and assumed to be an index of bronchoconstriction. We show that P-b(t) is determined largely by gas conditioning when normal mice breathe spontaneously inside a closed chamber in which the air is at ambient conditions. When the air in the chamber is heated and humidified to body conditions, the changes in P-b(t) are reduced by about two-thirds. The remaining changes are thus due to gas compression and expansion within the lung and are amplified when the animals breathe through increased resistances. We show that the time integral of P-b(t) over inspiration is accurately predicted by a term containing airway resistance, functional residual capacity, and tidal volume. We conclude that unrestrained plethysmography can be used to accurately characterize changes in airway resistance only if functional residual capacity and tidal volume are measured independently and the chamber gas is preconditioned to body temperature and humidity.
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- Lundblad, Lennart, et al.
(författare)
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Interpreting Penh in mice - Reply
- 2003
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 94:2, s. 831-832
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Lundblad, Lennart, et al.
(författare)
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Thoracic gas volume measurements in paralyzed mice
- 2004
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Ingår i: Annals of Biomedical Engineering. - 1573-9686. ; 32:10, s. 1420-1427
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Tidskriftsartikel (refereegranskat)abstract
- We have previously measured thoracic gas volume (V-TG) in spontaneously breathing mice using a whole body plethysmograph and have now extended our technique to allow for V-TG measurements during paralysis. BALB/c mice were anesthetized and placed in a body-box and ventilated via a tracheostomy cannula through the box wall. Box pressure (P-b) and tracheal pressure (P-ao) were measured during spontaneous breathing, and again after paralysis while mechanically compressing the chest. V-TG was much larger after paralysis (0.49+/-0.06 ml, positive end-expiratory pressure=2 cmH(2)O) when compared with spontaneous breathing (0.31+/-0.01 ml). External chest compression produced looping in the plots of P-b versus P-ao that was attributable to gradual changes in P-b upon release of the mechanical chest compression and had the character of thermal transients. Under the assumption that the rate of heating of the air in the chamber was proportional to the pressure applied to the animal's chest, and that any increase in air temperature was dissipated by heat absorption by the chamber walls, we developed an algorithm that corrected for the thermal events. This yielded similar results for V-TG (0.30+/-0.02 ml) as obtained during spontaneous efforts. Our method may prove particularly useful when paralysis is required for the precise measurement of lung mechanics.
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| 8. |
- Wagers, S, et al.
(författare)
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Nonlinearity of respiratory mechanics during bronchoconstriction in mice with airway inflammation
- 2002
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 92:5, s. 1802-1807
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory system resistance (R) and elastance (E) are commonly estimated by fitting the linear equation of motion P = EV + R(V) over dot + P-0 (Eq. 1) to measurements of respiratory pressure (P), lung volume (V), and flow (V). However, the respiratory system is unlikely to behave linearly under many circumstances. We determined the importance of respiratory system nonlinearities in two groups of mechanically ventilated Balb/c mice [controls and mice with allergically inflamed airways (ova/ova)], by,g the impact of the addition of nonlinear terms (E2V2 assessing and R-2(V) over dot (V) over dot) on the goodness of model fit seen with Eq. 1. Significant improvement in fit (51.85 +/- 4.19%) was on seen in the ova/ova mice during bronchoconstriction when the E2V2 alone was added. An improvement was also observed with addition of the E2V2 term in mice with both low and high lung volumes ventilated at baseline, suggesting a volume-dependent nonlinearity of E. We speculate that airway closure in the constricted ova/ova mice accentuated the volume-dependent nonlinearity by decreasing lung volume and overdistending the remaining lung.
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- Wagers, S, et al.
(författare)
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The allergic mouse model of asthma: normal smooth muscle in an abnormal lung?
- 2004
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 96:6, s. 2019-2027
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Tidskriftsartikel (refereegranskat)abstract
- Mice with allergically inflamed airways are widely used as animal models of asthma, but their relevance for human asthma is not understood. We, therefore, examined the time course of changes in respiratory input impedance during induced bronchoconstriction in BALB/c mice sensitized and challenged with ovalbumin. Our results indicate that bronchoconstriction in mice is accompanied by complete closure of substantial regions of the lung and that closure increases markedly when the lungs are allergically inflamed. With the aid of an anatomically accurate computational model of the mouse lung, we show that the hyperresponsiveness of mice with allergically inflamed airways can be explained entirely by a thickening of the airway mucosa and an increased propensity of the airways to close, without the involvement of any increase in the degree of airway smooth muscle shortening. This has implications for the pathophysiology of asthma and suggests that at least some types of asthma may benefit from therapies aimed at manipulating surface tension at the air-liquid interface in the lungs.
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