Effects of salbutamol and Ro-20-1724 on airway and parenchymal mechanics in rats

Abstract

We investigated the effects of a selective beta(2)-agonist, salbutamol, and of phosphodiesterase type 4 inhibition with 4-(3-butoxy-4-methoxy benzyl)-2-imidazolidinone (Ro-20-1724) on the airway and parenchymal mechanics during steady-state constriction induced by MCh administered as an aerosol or intravenously (iv). The wave-tube technique was used to measure the lung input impedance (ZL) between 0.5 and 20 Hz in 31 anesthetized, paralyzed, open-chest adult Brown Norway rats. To separate the airway and parenchymal responses, a model containing an airway resistance (Raw) and inertance (Iaw), and a parenchymal damping (G) and elastance (H), was fitted to ZL spectra under control conditions, during steady-state constriction, and after either salbutamol or Ro-20-1724 delivery. In the Brown Norway rat, the response to iv MCh infusion was seen in Raw and G, whereas continuous aerosolized MCh challenge produced increases in G and H only. Both salbutamol, administered either as an aerosol or iv, and Ro-20-1724 significantly reversed the increases in Raw and G when MCh was administered iv. During the MCh aerosol challenge, Ro-20-1724 significantly reversed the increases in G and H, whereas salbutamol had no effect. These results suggest that, after MCh-induced changes in lung function, salbutamol increases the airway caliber. Ro-20-1724 is effective in reversing the airway narrowings, and it may also decrease the parenchymal constriction.

Hyperoxia-induced changes in mouse lung mechanics: forced oscillations vs. barometric plethysmography

“…Our Zrs spectra are qualitatively similar to those obtained in previous studies in rats (29,30), in guinea pigs (1), and in mice (16). In agreement with previous findings (1,16,19,23,29,30), the model involving an airway and a constant-phase tissue compartment was consistent with the frequency dependence of Zrs.…”

“…The wave-tube technique (36) was adapted to measure forced oscillatory Zrs in mice. This technique was specially designed to measure the input impedance of rats (29,30) and guinea pigs (1) without the need for estimation of the oscillatory flow. We miniaturized the setup to reduce the ventilatory dead space (40 l) and to adjust its impedance to the expected high load impedance of the mouse.…”

“…the small size of the animal. We therefore adapted the wave-tube technique of forced oscillations, the lowfrequency version of which has been validated in rats (23,29) and has been shown to provide a separate estimation of airway and tissue parameters (1,16,19,23,29,30). These previous investigations demonstrated that lung mechanical parameters identified from low-frequency input impedance data characterize the mechanical conditions of the airways and the respiratory tissues accurately in a healthy and moderately or homogeneously constricted lung (23,29).…”

“…Numerous studies have demonstrated decreases in the compliance of the lungs (2,8,10,11,13,14,25) or of the total respiratory system (26,35) and in the vital capacity (13) after oxygen exposure. We argue, however, that the previously reported marked increases in the resistance of the total respiratory system (Rrs) or of the lungs (RL) (10,11,13,14,26,31,34,35) do not necessarily reflect alterations in the airway function because these global resistive parameters incorporate a significant component related to the respiratory tissues (Rti) (1,16,18,19,23,29,30).…”

“…Although the study of mouse lung pathophysiology has gained ground in asthma models and other pathological lung conditions, including hyperoxia (2)(3)(4)(5)25), very few techniques are available to estimate the lung function in mice. The low-frequency forced oscillation technique (LFOT) and model-based evaluation of respiratory system impedance (Zrs) data have been used in various mammals to partition RL into airway and parenchymal components under control conditions and during lung constriction (1,16,19,23,29,30). Small laboratory animals also have been investigated extensively by the wave-tube version of this technique, and the results were successfully validated in rats (23,29).…”