Effects of Central Airway Shunting on the Mechanical Impedance of the Mouse Lung

Abstract

The mechanical properties of the lung are embodied in its mechanical input impedance, which it is interpreted in physiological terms by being fit with a mathematical model. The normal lung is extremely well described by a model consisting of a single uniformly ventilated compartment comprised of tissue having a constant-phase impedance, but to describe the abnormal lung it frequently becomes necessary to invoke additional compartments. To date, all evidence of regional mechanical heterogeneity in the mouse lung has been assumed to be of the parallel variety. We therefore investigated the use of a serial heterogeneity model, relative to parallel heterogeneity and homogeneous models, for describing impedance spectra in mice subjected to a variety of interventions designed to make their lungs heterogeneous. We found that functional evidence of the finite stiffness of the airway wall in mice with airways obstruction can sometimes be apparent in lung impedance below 20 Hz. The model estimates of airway stiffness were smaller than direct estimates obtained from micro-CT images of the lung in vivo, suggesting that the conducting airways alone are likely not the precise anatomical correlate of proximal functional stiffness in the lung. Nevertheless, we conclude that central airway shunting in mice can sometimes be an important physiological phenomenon.

Evaluation of Respiratory System Mechanics in Mice using the Forced Oscillation Technique

“…However the latter are associated with a great deal of uncertainty as to the basis of their outcomes and are viewed by many as being flawed 1 . Repeated invasive measurements are possible in orally intubated animals, although technically more challenging 17 .…”

“…However, severely bronchoconstricted animals could be assessed by analyzing Zrs directly 15 , or by using third party post-analysis software to fit more complex mathematical models, e.g. taking into account the heterogeneity of mechanical function 17 . Excluded datasets can also be observed if the animal's airways are not sufficiently passive or if the resistance of the cannula is too high.…”

Airway responsiveness depends on the diffusion rate of methacholine across the airway wall

“…This would correspond to a 2% increase in wall thickness in an airway of 1-mm diameter. Interestingly, this is about the size of the largest airways in a BALB/c mouse (21), which perhaps can be taken to indicate some level of consistency. This being the case, our results concur with those of our laboratory's previous study (24), which led to the conclusion that the hyperresponsiveness of the acutely allergically inflamed BALB/c mouse can be explained virtually entirely as being due to a thickening of the airway epithelium.…”

“…We studied two groups of BALB/c mice at 8 -12 wk of age and 18 -22 g (Jackson Laboratories, Bar Harbor, ME) that were sensitized with two intraperitoneal injections of ovalbumin (100 g) in alum (2.25 mg), given on days 1 and 14, after first having been acclimatized in our animal facility for 3 days. One group (the control group) was then exposed to an aerosol of saline for 30 min on days 21,22, and 23. The other group (the OVA group) was challenged by exposure to an aerosol of 1% ovalbumin for 30 min on days 21, 22, and 23.…”

Análise da aplicação do modelo de fase constante na avaliação da mecânica respiratória em animais durante broncoconstrição.

“…Na literatura corrente, há um crescente número de artigos que realizam a avaliação da mecânica respiratória em pequenos animais ventilados mecanicamente (BURBURAN et al, 2014;HANIFI et al, 2012;MORIYA;MORAES;SCHWARTZ et al, 2011;WALKER;KRAFT;FISHER, 2012), assim como o do presente trabalho e isto é devido a necessidade de fomentar áreas como a avaliação da mecânica respiratória.…”