Deep Inhalation Prevents the Respiratory Elastance Response to Methacholine in Rats

Abstract

ABSTRACT:The bronchodilator effect of deep inhalation (DI) may be assessed from the time course of respiratory system resistance (Rrs) and reactance (Xrs) measured by the forced oscillation technique at a single frequency. The aim of the study was to assess the effect of DI in the closed chest rat. Under anesthesia and mechanical ventilation, seven Brown Norway rats were given regular DI (BN-di) and six underwent continuous tidal ventilation (BN) throughout an otherwise similar methacholine (Mch) challenge protocol. Rrs and Xrs were monitored at 20 Hz and apparent respiratory system elastance (Ers) was computed from Xrs. After Mch nebulization, there was a significant increase in Rrs and Ers compared with saline. Ers, but not Rrs, decreased after the DI and BN-di were found to have lower Ers than BN. Thus, DI significantly alters Ers and its response to Mch. Computer simulations suggested reversal of increased viscoelasticity and/or inhomogeneous behavior by the DI in that model. R ecent technological progress has promoted a number of methods for the study of respiratory function in subjects that show little cooperation capability. The forced oscillation technique is used in young children to measure the mechanical impedance of the respiratory system (Zrs). An externally generated periodic flow of small amplitude is delivered at the airway opening. Excitation frequencies may range from very low (Ͻ0.5 Hz) to very high (Ͼ50 Hz). In routine pediatric practice, however, the operating range is narrower. The use of very low frequencies is limited by the breathing of the subject and the upper airway wall motion is responsible for significant artefact at higher frequencies (1,2). As a result, most of the relevant information on respiratory mechanical properties in children so far appear to have been obtained somewhere between 5 and 15 Hz (3). The use of a single excitation frequency allows tracking Zrs changes during breathing (4 -6), which is of particular interest in view of the significant time-dependent alteration in airway function that may be observed after a deep inhalation (DI) (7,8). A decrease in airway resistance after a DI is thus highly suggestive of reversal of bronchoconstriction (9 -12). Therefore, the airway response to a DI has the capability of assessing the mechanisms of airway obstruction and has recently been applied to the study of airway hyperresponsiveness in children using the forced oscillation technique (5,13,14).Whole animal experiments are potentially useful to assess mechanisms through which a DI acts on the airways and to contribute to validating the techniques used in the routine lung function laboratory. Most studies in experimental animals are performed on lung mechanics, i.e. in open-chest condition (12,15-17), which is not representative of the conditions in the pediatric respiratory function laboratory. Airway responsiveness to Mch has been shown in the Brown Norway rat (18,19), and there are few data on how respiratory mechanics may be affected by the occurrence of DI in that model...

Deep inspirations protect against airway closure in nonasthmatic subjects

“…Their computational modeling suggested that avoiding DIs results in uneven constriction involving heterogeneous airway closure or near closure. A similar protective effect of DIs against increases in respiratory system elastance, with no effect on resistance, has been demonstrated in rats (23). None of the subjects in the present study had evidence of expiratory flow limitation as previously proposed (10).…”

“…The mechanisms by which DIs protect against AHR are not well understood. DI avoidance in rats leads to increased elastance after methacholine challenge, with no effect on resistance, suggesting a purely peripheral airway effect (23). Using the forced oscillation technique (FOT) to make measurements of lung resistance and elastance, Lutchen et al (16) showed that DI avoidance produced a greater response to methacholine at oscillation frequencies between 0.1 and 2 Hz, indicating peripheral airway changes.…”

Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice

“…This indicates that DI has a stronger effect on peripheral tissue in the chronic airway inflammation and that the protective effect of DI on lung resistance is greater in acute airway inflammation. Our results in the chronic airway inflammation are in line with those of Schweitzer et al [ 24 ], who showed that DI in Brown Norway rats, protected against MCh-induced increases in respiratory system elastance, but not resistance. Similar results were previously found by Hirai and Bates [ 25 ], who showed that DI, in healthy Sprague-Dawley rats, was neither bronchodilatory nor bronchoprotective, but indeed had a significant effect on both tissue damping and tissue elastance.…”

“…The airway protective effects of DI are similar to what has also been seen in other animal studies [ 24 - 27 ] and in humans [ 5 - 7 , 28 ]. The mechanisms underlying this bronchoprotective effect are not clear, but several hypotheses have been put forward as to how DI confers bronchoprotection [ 9 ], in which the main mechanisms have been suggested to be neural, nitric oxide (NO)-mediated, or mechanical.…”