To determine the predominant site of action of methacholine (MCh) on lung mechanics, two groups of open-chest Sprague-Dawley rats were studied. Five rats were measured during intravenous infusion of MCh (i.v. group), with doubling of concentrations from 1 to 16 micrograms.kg-1.min-1. Seven rats were measured after aerosol administration of MCh with doses doubled from 1 to 16 mg/ml (ae group). Pulmonary input impedance (ZL) between 0.5 and 21 Hz was determined by using a wave-tube technique. A model containing airway resistance (Raw) and inertance (Iaw) and parenchymal damping (G) and elastance (H) was fitted to the ZL spectra. In the iv group, MCh induced dose-dependent increases in Raw [peak response 270 +/- 9 (SE) % of the control level; P < 0.05] and in G (340 +/- 150%; P < 0.05), with no increase in Iaw (30 +/- 59%) or H (111 +/- 9%). In the ae group, the dose-dependent increases in Raw (191 +/- 14%; P < 0.05) and G (385 +/- 35%; P < 0.05) were associated with a significant increase in H (202 +/- 8%; P < 0.05). Measurements with different resident gases [air vs. neon-oxygen mixture, as suggested (K.R. Lutchen, Z. Hantos, F. Peták, A. Adamicza, and B. Suki J. Appl. Physiol. 80: 1841-1849, 1996)] in the control and constricted states in another group of rats suggested that the entire increase seen in G during the i.v. challenge was due to ventilation inhomogeneity, whereas the ae challenge might also have involved real tissue contractions via selective stimulation of the muscarinic receptors.

We observed that cardiopulmonary bypass deteriorates lung function by inducing a heterogeneous airway constriction, whereas no such effects were observed in patients undergoing cardiac surgery without bypass. The impairment in parenchymal mechanics, which was obtained in both groups, may result from peripheral airway closure and/or be a consequence of mediator release.

Electrical stimulation of intercostal muscles was employed to measure thoracic gas volume (TGV) during airway occlusion in the absence of respiratory effort at different levels of lung inflation. In 15 tracheostomized and mechanically ventilated CBA/Ca mice, the value of TGV obtained from the spontaneous breathing effort available in the early phase of the experiments (TGVsp) was compared with those resulting from muscle stimulation (TGVst) at transrespiratory pressures of 0, 10, and 20 cmH2O. A very strong correlation (r2= 0.97) was found, although with a systematically (approximately 16%) higher estimation of TGVst relative to TGVsp, attributable to the different durations of the stimulated (approximately 50 ms) and spontaneous (approximately 200 ms) contractions. Measurements of TGVst before and after injections of 0.2, 0.4, and 0.6 ml of nitrogen into the lungs in six mice resulted in good agreement between the change in TGVst and the injected volume (r2= 0.98). In four mice, TGVsp and TGVst were compared at end expiration with air or a helium-oxygen mixture to confirm the validity of isothermal compression in the alveolar gas. The TGVst values measured at zero transrespiratory pressure in all CBA/Ca mice [0.29 +/- 0.05 (SD) ml] and in C57BL/6 (N = 6; 0.34 +/- 0.08 ml) and BALB/c (N = 6; 0.28 +/- 0.06 ml) mice were in agreement with functional residual capacity values from previous studies in which different techniques were used. This method is particularly useful when TGV is to be determined in the absence of breathing activity, when it must be known at any level of lung inflation or under non-steady-state conditions, such as during pharmaceutical interventions.

During slow inflation of lung lobes, we measure a sequence of short explosive transient sound waves called "crackles," each consisting of an initial spike followed by ringing. The crackle time series is irregular and intermittent, with the number of spikes of size s following a power law, n(s) proportional, variants(-alpha), with alpha=2.77+/-0.05. We develop a model of crackle wave generation and propagation in a tree structure that combines the avalanchelike opening of airway segments with the wave propagation of crackles in a tree structure. The agreement between experiments and simulations suggests that (i) the irregularities are a consequence of structural heterogeneity in the lung, (ii) the intermittent behavior is due to the avalanchelike opening, and (iii) the scaling is a result of successive attenuations acting on the sound spikes as they propagate through a cascade of bifurcations along the airway tree.

Although viscosity (mu) is a crucial factor in measurements of flow with a pneumotachograph, and density (rho) also plays a role in the presence of turbulent flow, these material constants are not available for the volatile anaesthetic agents commonly administered in clinical practice. Thus, we determined experimentally mu and rho of pure volatile anaesthetic agents. Input impedance of a rigid-wall polyethylene tube (Zt) was measured when the tube was filled with various mixtures of carrier gases (air, 100% oxygen, 50% oxygen+50% nitrogen) to which different concentrations of volatile anaesthetic inhalation agents (halothane, isoflurane, sevoflurane, and desflurane) had been added. Mu and rho were calculated from real and imaginary portions of Zt, respectively, using the appropriate physical equations. Multiple linear regression was applied to estimate mu and rho of pure volatile agents. Viscosity values of pure volatile agents were markedly lower than those for oxygen or nitrogen. Clinically applied concentrations, however, did not markedly affect the viscosity of the gas mixture (maximum of 3.5% decrease in mu for 2 MAC desflurane). In contrast, all of the volatile agents significantly affected rho even at routinely used concentrations. Our results suggest that the composition of the carrier gas has a greater impact on viscosity than the amount and nature of the volatile anaesthetic agent whereas density is more influenced by volatile agent concentrations. Thus, the need for a correction factor in flow measurements with a pneumotachograph depends far more on the carrier gas than the concentration of volatile agent administered, although the latter may play a role in particular experimental or clinical settings.