Acoustic evidence of airway opening during recruitment in excised dog lungs.

The aim of this study was to test the hypothesis that the mechanism of recruitment and the lower knee of the pressure-volume curve in the normal lung are primarily determined by airway reopenings via avalanches rather than simple alveolar recruitments. In isolated dog lung lobes, the pressure-volume loops were measured, and crackle sounds were recorded intrabronchially during both the first inflation from the collapsed state to total lobe capacity and a second inflation without prior degassing. The inflation flow contained transients that were accompanied by a series of crackles. Discrete volume increments were estimated from the flow transients, and the energy levels of the corresponding crackles were calculated from the sound recordings. Crackles were concentrated in the early phase of inflation, with the cumulative energy exceeding 90% of its final value by the lower knee of the pressure-volume curve. The values of volume increments were correlated with crackle energy during the flow transient for both the first and the second inflations (r(2) = 0.29-0.73 and 0.68-0.82, respectively). Because the distribution of volume increments followed a power law, the correlation between crackle energy and discrete volume increments suggests that an avalanche-like airway opening process governs the recruitment of collapsed normal lungs.

Components of respiratory resistance monitored in mechanically ventilated patients.

The interrupter technique is commonly adopted to monitor respiratory resistance (Rrs,int) during mechanical ventilation; however, Rrs,int is often interpreted as an index of airway resistance (Raw). This study compared the values of Rrs,int provided by a Siemens 940 Lung Mechanics Monitor with total respiratory impedance (Zrs) parameters in 39 patients with normal spirometric parameters, who were undergoing elective coronary bypass surgery. Zrs was determined at the airway opening with pseudorandom oscillations of 0.2-6 Hz at end inspiration. Raw and tissue resistance (Rti) were derived from the Zrs data by model fitting; Rti and total resistance (Rrs,osc=Raw+Rti) were calculated at the actual respirator frequencies. Lower airway resistance (Rawl) was estimated by measuring tracheal pressure. Although good agreement was obtained between Rrs,osc and Rrs,int, with a ratio of 1.07+/-0.19 (mean+/-SD), they correlated poorly (r2=0.36). Rti and the equipment component of Raw accounted for most of Rrs,osc (39.8+/-11.9 and 43.0+/-6.9%, respectively), whereas only a small portion belonged to Rawl (17.2+/-6.3%). It is concluded that respiratory resistance may become very insensitive to changes in lower airway resistance and therefore, inappropriate for following alterations in airway tone during mechanical ventilation, especially in patients with relatively normal respiratory mechanics, where the tissue and equipment resistances represent the vast majority of the total resistance.

Concentration- and time-dependent effect of aminooxyacetic acid on cortical epileptogenicity.

In the present electrophysiological study the effect of aminooxyacetic acid (AOAA) on the cortical epileptogenicity, and on the basic electro-cortical activity was investigated in anesthetized rats. AOAA did not induce spontaneous epileptiform discharges but modified the somato-sensory evoked responses and the cortical epileptogenicity (induced by 4-aminopyridine) in the same manner depending on its concentration. AOAA at low concentrations increased the amplitude of evoked responses and the ipsilateral manifestation of epileptiform activity, however, at high concentrations significantly suppressed both the evoked responses and the induction and expression of seizures discharges. The anticonvulsive effect of AOAA was time-dependent (reached its maximum after 2h AOAA pre-treatment) and reversible. AOAA at low concentrations probably increases the efficacy of the NMDA excitatory system and decreases GABA-synthesis, resulting neuronal hyperexcitation. However, AOAA at high concentrations can lead to an effective cortical inhibition through intra- and extracellular accumulation of GABA. The gradual GABA accumulation - up to a certain level - at the synapses could also explain the time-dependency of the anticonvulsive effect of AOAA.

Endothelin-1-induced airway and parenchymal mechanical responses in guinea-pigs: the roles of ETA and ETB receptors.

Endothelin-1 (ET-1) has been shown to have a constrictor effect on the airways and parenchyma; however, the roles of the ETA and ETB receptors in the ET-1-induced changes in the airway and tissue compartments have not been fully explored. Low-frequency pulmonary impedance (ZL) was measured in anaesthetized, paralysed, open-chest guinea-pigs. ZL spectra were fitted by a model to estimate airway resistance (Raw) and inertance (Iaw), and coefficients of tissue damping (G) and elastance (H), and hysteresivity (eta = G/H). Two successive doses of ET-1 (0.05 and 0.2 nmol x kg(-1)) each evoked significant dose-related increases in Raw, G, H and eta. Pretreatment with 20 nmol x kg(-1) BQ-610 (a highly selective ETA receptor antagonist) resulted in a significantly decreased elevation only in H after the lower dose of ET-1. However, all parameters changed significantly less on the administration of ET-1 after pretreatment with 80 nmol-kg(-1) BQ-610, with 20 nmol x kg(-1) ETR-P1/fl (a novel ETA receptor antagonist) or with 20 nmol x kg(-1) IRL 1038 (an ETB receptor antagonist). The results of the separate assessments of the airway and tissue mechanics demonstrate that endothelin-1 induces airway and parenchymal constriction via stimulation of both receptor types in both compartments.

Viscosity and density of common anaesthetic gases: implications for flow measurements.

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.

Size distribution of recruited alveolar volumes in airway reopening.

In 11 isolated dog lung lobes, we studied the size distribution of recruited alveolar volumes that become available for gas exchange during inflation from the collapsed state. Three catheters were wedged into 2-mm-diameter airways at total lung capacity. Small-amplitude pseudorandom pressure oscillations between 1 and 47 Hz were led into the catheters, and the input impedances of the regions subtended by the catheters were continuously recorded using a wave tube technique during inflation from -5 cm H(2)O transpulmonary pressure to total lung capacity. The impedance data were fit with a model to obtain regional tissue elastance (Eti) as a function of inflation. First, Eti was high and decreased in discrete jumps as more groups of alveoli were recruited. By assuming that the number of opened alveoli is inversely proportional to Eti, we calculated from the jumps in Eti the distribution of the discrete increments in the number of opened alveoli. This distribution was in good agreement with model simulations in which airways open in cascade or avalanches. Implications for mechanical ventilation may be found in these results.

Effects of endothelin-1 on airway and parenchymal mechanics in guinea-pigs.

The contributions of the airways and the parenchyma to the overall lung mechanical response to endothelin-1 (ET-1) have not been systematically studied. In this investigation, the ET-1 induced changes on lung mechanics in guinea-pigs were separated into airway and parenchymal components. Pulmonary impedance (ZL) data were collected between 0.5 and 21 Hz in six anaesthetized, paralysed, open-chest animals by introducing small-amplitude pseudorandom oscillations into the trachea through a wave tube. ZL was calculated before and following intravenous boluses of ET-1, with doses doubled from 0.125-2 microg x kg of body weight(-1). A model containing an airway resistance (Raw) and inertance (Iaw) and tissue damping (G) and elastance (H) was fitted to the ZL spectra in each condition. Parenchymal hysteresis (eta) was calculated as G/H. After each dose, ET-1 induced significant increases in Raw (at peak response mean+/-SEM: 424+/-129%), G (400+/-80%), H (95+/-22%) and eta (156+/-33%), whereas Iaw decreased following the two highest doses (-291+/-77%). These data suggest that the parenchymal constriction was accompanied by inhomogeneous constriction of the peripheral airways.

Scaling behavior in crackle sound during lung inflation.

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.

Methacholine-induced bronchoconstriction in rats: effects of intravenous vs. aerosol delivery.

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.

Mechanical impedance of the lung periphery.

The mechanics of the regional airways and tissues was studied in isolated dog lobes by means of a modified wave-tube technique. Small-amplitude pseudorandom forced oscillations between 0.1 and 48 Hz were applied through catheters wedged in 2-mm-diameter bronchi in three regions of each lobe at translobar pressures (PL) of 10, 7, 5, 3, 2, and 1 cmH2O. The measured regional input impedances were fitted by a model containing the resistance (R1) and inertance (I) of the regular (segmental) airways, the resistance of the collateral channels (R2), and the damping (G) and elastance (H) of the local tissues. This model gave far better fits to the data on impedance of the lung periphery than when G and H were replaced by a single tissue compliance, which explains why interruption of segmental flow did not lead to monoexponential pressure decay in previous studies. The interlobar and intralobar variances of the parameters were equally significant, and poor correlations were found between the airway parameters R1 and R2 and between any airway and tissue parameter (e.g., R1 and H). R2 was on average approximately 10 times higher than R1, although the R2-to-R1 ratios and their dependencies on PL were regionally highly variable. However, for the total of 33 regions studied, the PL dependence was the same for R1 and R2, which may reflect similar morphological structures for the regular and collateral airways. The dependencies of G and H on PL showed high interregional variations; generally, however, they assumed their minima at medium PL values (approximately 5 cmH2O).