Repeated measurements of airway and parenchymal mechanics in rats by using low-frequency oscillations

For studies investigating the mechanisms underlying the development of allergic conditions such as asthma, noninvasive methodologies for separating airway and parenchymal mechanics in animal models are required. To develop such a method, seven Brown Norway rats were studied on three occasions over a 14-day period. After the baseline measurements, on the third day inhaled methacholine was administered. Once lung function returned to the baseline level, a thoracotomy was performed to compare the lung mechanics in the intact- and open-chest conditions. On each occasion, the rats were anesthetized, paralyzed, and intubated. Small-amplitude oscillations between 0.5 and 21 Hz were applied through a wave tube to obtain respiratory impedance (Zrs). Esophageal pressure was measured to separate Zrs into pulmonary (ZL) and chest wall (Zw) components. A model containing a frequency-independent resistance and inertance and a tissue component, including tissue damping and elastance, was fitted to Zrs, ZL, and Zw spectra. Measurements of Zrs, ZL, or Zw and the model parameters calculated from them did not differ among tests. The number of animals required to show group changes in lung mechanics was significantly lower when animals were measured noninvasively than when the group changes were calculated from open-chest measurements. In conclusion, the method reported in this study can be used to separate airway and lung tissue mechanics noninvasively over a series of tests and can detect pulmonary constrictor responses for the airways and the parenchyma separately.