Comparison between neurally-assisted, controlled, and physiologically variable ventilation in healthy rabbits.

BACKGROUND: Various ventilation strategies have been proposed to reduce ventilation-induced lung injury that occurs even in individuals with healthy lungs. We compared new modalities based on an individualised physiological variable ventilation model to a conventional pressure-controlled mode. METHODS: Rabbits were anaesthetised and ventilated for up to 7 h using pressure-controlled ventilation with (Group PCS, n=10), and without (Group PC, n=10) regular sighs. Variable ventilation in the other two groups was achieved via a pre-recorded spontaneous breathing pattern [Group physiologically variable ventilation (PVV), n=10] or triggered by the electrical activity of the diaphragm [Group neurally adjusted ventilation assist (NAVA), n=9]. Respiratory elastance, haemodynamic profile, and gas exchange were assessed throughout the ventilation period. Cellular profile, cytokine content of bronchoalveolar lavage fluid, and wet-to-dry lung weight ratio (W/D) were determined after protocol completion. Lung injury scores were obtained from histological analysis. RESULTS: Marked deteriorations in elastance were observed (median and 95% confidence interval) in Group PC [48.6 (22)% increase from baseline], while no changes were detected in Groups PCS [3.6 (8.1)%], PVV [18.7 (13.2)%], and NAVA [-1.4 (12.2)%]. In comparison with Group PC, Group PVV had a lower lung injury score [0.29 (0.02) compared with 0.36 (0.05), P<0.05] and W/D ratio [5.6 (0.1) compared with 6.2 (0.3), P<0.05]. There was no difference in blood gas, haemodynamic, or inflammatory parameters between the groups. CONCLUSIONS: Individualised PVV based on a pre-recorded spontaneous breathing pattern provides adequate gas exchange and promotes a level of lung protection. This ventilation modality could be of benefit during prolonged anaesthesia, in which assisted ventilation is not possible because of the absence of a respiratory drive.

Quantitative Imaging of Regional Aerosol Deposition, Lung Ventilation and Morphology by Synchrotron Radiation CT.

To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. No single imaging modality allows the acquisition of all such data together. Here we assessed the feasibility of dual-energy synchrotron radiation imaging to this end in anesthetized rabbits; both in normal lung (n = 6) and following methacholine (MCH)-induced bronchoconstriction (n = 6), a model of asthma. We used K-edge subtraction CT (KES) imaging to quantitatively map the regional deposition of iodine-containing aerosol particles. Morphological and regional ventilation images were obtained, followed by quantitative regional iodine deposition maps, after 5 and 10 minutes of aerosol administration. Iodine deposition was markedly inhomogeneous both in normal lung and after induced bronchoconstrition. Deposition was significantly reduced in the MCH group at both time points, with a strong dependency on inspiratory flow in both conditions (R2 = 0.71; p < 0.0001). We demonstrate for the first time, the feasibility of KES CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology. Since these are among the main factors determining lung aerosol deposition, we expect this imaging approach to bring new contributions to the understanding of lung aerosol delivery, targeting, and ultimately biological efficacy.

Capnogram slope and ventilation dead space parameters: comparison of mainstream and sidestream techniques.

BACKGROUND: Capnography may provide useful non-invasive bedside information concerning heterogeneity in lung ventilation, ventilation-perfusion mismatching and metabolic status. Although the capnogram may be recorded by mainstream and sidestream techniques, the capnogram indices furnished by these approaches have not previously been compared systematically. METHODS: Simultaneous mainstream and sidestream time and volumetric capnography was performed in anaesthetized, mechanically ventilated patients undergoing elective heart surgery. Time capnography was used to assess the phase II (SII,T) and III slopes (SIII,T). The volumetric method was applied to estimate phase II (SII,V) and III slopes (SIII,V), together with the dead space values according to the Fowler (VDF), Bohr (VDB), and Enghoff (VDE) methods and the volume of CO2 eliminated per breath ([Formula: see text]). The partial pressure of end-tidal CO2 ([Formula: see text]) was registered. RESULTS: Excellent correlation and good agreement were observed in SIII,T measured by the mainstream and sidestream techniques [ratio=1.05 (sem 0.16), R(2)=0.92, P<0.0001]. Although the sidestream technique significantly underestimated [Formula: see text] and overestimated SIII,V [1.32 (0.28), R(2)=0.93, P<0.0001], VDF, VDB, and VDE, the agreement between the mainstream and sidestream techniques in the difference between VDE and VDB, reflecting the intrapulmonary shunt, was excellent [0.97 (0.004), R(2)=0.92, P<0.0001]. The [Formula: see text] exhibited good correlation and mild differences between the mainstream and sidestream approaches [0.025 (0.005) kPa]. CONCLUSIONS: Sidestream capnography provides adequate quantitative bedside information about uneven alveolar emptying and ventilation-perfusion mismatching, because it allows reliable assessments of the phase III slope, [Formula: see text] and intrapulmonary shunt. Reliable measurement of volumetric parameters (phase II slope, dead spaces, and eliminated CO2 volumes) requires the application of a mainstream device.

Perioperative use of oxygen: variabilities across age.

Enormous interest has emerged in the perioperative use of high concentrations of inspired oxygen in an attempt to increase tissue oxygenation and thereby improve postoperative outcome. An extensive debate has arisen regarding the risk/benefit ratio of oxygen therapy, with some researchers advocating the benefits of perioperative hyperoxia, particularly with regard to surgical site infection, whereas others emphasize its detrimental consequences on multiple organs, particularly the lungs and the brain. As one aspect of this debate, there is increased awareness of effects of reactive oxygen metabolites, a feature that contributes to the complexity of achieving consensus regarding optimum oxygen concentration in the perioperative period. Many reviews have discussed the pros and cons in the use of perioperative oxygen supplementation, but the potential importance of age-related factors in hyperoxia has not been addressed. The present narrative review provides a comprehensive overview of the physiological mechanisms and clinical outcomes across the age range from neonates to the elderly. Risks greatly outweigh the benefits of hyperoxia both in the very young, where growth and development are the hallmarks, and in the elderly, where ageing increases sensitivity to oxidative stress. Conversely, in middle age, benefits of short-term administration of perioperative oxygen therapy exceed potential adverse change effects, and thus, oxygen supplementation can be considered an important therapy to improve anaesthesia management.

Implication of dipeptidylpeptidase IV activity in human bronchial inflammation and in bronchoconstriction evaluated in anesthetized rabbits.

BACKGROUND: Decreased dipeptidylpeptidase IV (DPPIV) activity within the human nasal mucosa has previously been shown to contribute to the severity of chronic inflammatory rhinosinusitis. OBJECTIVE: To investigate and correlate the role of DPPIV activity with regard to bronchial inflammation. METHODS: DPPIV/CD26 activity/concentration was investigated in the bronchial tissue of human subjects suffering from chronic bronchial inflammation. In addition, the effect of a recombinant Aspergillus fumigatus DPPIV (fuDPPIV) was investigated on histamine-induced bronchoconstriction in anesthetized rabbits. RESULTS AND CONCLUSIONS: DPPIV/CD26 was present in submucosal seromucous glands, in leukocytes and to a very low degree in endothelial cells of human bronchi. DPPIV activity was correlated with tissue CD26 content measured by immunoassay. As previously reported for the nasal mucosa, DPPIV/CD26 activity was inversely correlated with the degree of airway inflammation. Systemic pretreatment with recombinant fuDPPIV markedly reduced the increase in histamine-induced airway resistance in rabbits. In conclusion, DPPIV activity modulates lower airway tone by degrading unknown peptidic substrates released by histamine in response to an allergen. Contrasting with our observations in the nose, this modulation is apparently not mediated via a neurokinin (NK1) receptor.

Protective effects of volatile agents against acetylcholine-induced bronchoconstriction in isolated perfused rat lungs.

BACKGROUND: Bronchoactive properties of volatile agents against lung constriction are well established. The purpose of this study was to investigate the ability of halothane (Hal), isoflurane (Iso), sevoflurane (Sev) and desflurane (Des) to alter the lung mechanics in the absence of an airway tone and during acetylcholine (Ach)-induced bronchoconstriction. METHODS: Low-frequency pulmonary impedance data (ZL) were collected from isolated, normo-perfused rat lungs under baseline conditions and following the injection of Ach (0.1 mg/kg) into the pulmonary artery. Measurements were performed without the administration of any anaesthetic agent in the first phase of the experiments and during inhalation without any volatile agent (control group, n = 6) or during inhalation of Hal (n = 6), Iso (n = 9), Sev (n = 6) or Des (n = 8) at 1 minimum alveolar concentration (MAC). The airway resistance (Raw) and parenchymal damping and elastance were estimated from the Z(L) data by model fitting. RESULTS: Under baseline conditions, the basic value of Raw was significantly decreased by Des (- 31.2 +/- 3.8%) and Sev (- 18.0 +/- 4.5%) administration, whereas Hal and Iso did not have a statistically significant effect on Raw (- 3.3 +/- 5.1% and - 8.6 +/- 2.4%, respectively). Moreover, all four inhalation anaesthetics prevented the increase in Raw following Ach administration, the findings ranging between - 14.3 +/- 11.4% for Hal and - 37.5 +/- 10.9% for Sev. CONCLUSIONS: Our results on a denervated isolated perfused lung model demonstrate the potential of Des and Sev to decrease the basal airway tone, whereas Iso and Hal are ineffective in this regard. All of these volatile agents markedly protect against Ach-induced bronchoconstriction.

Crackle-sound recording to monitor airway closure and recruitment in ventilated pigs.

It was hypothesised that the recruitment of atelectatic lung areas is signified by changes in the airway and tissue mechanics, and by the appearance of crackle activity attributed to the sudden reopening of collapsed airways. The authors also assumed that the acoustic activity is an earlier indicator of lung recruitment than the change in the overall mechanical state of the lungs. Six thoracotomised and mechanically ventilated mini-pigs were studied. Low-frequency pulmonary impedance was measured at end-expiratory pauses at transpulmonary pressures of 4 and 1 hPa to estimate airway resistance (Raw) and the coefficient of lung tissue elastance (H), and tracheal sounds were recorded during subsequent slow inflations to 30 hPa, in the control state and following increasing doses of i.v. methacholine (Mch). Raw and H were higher at baseline and increased more in response to Mch at 1 hPa than at 4 hPa. The crackles detected during the subsequent inflations were concentrated around and associated with the development of the lower knee of the pressure-volume curve. The number of crackles increased faster following the Mch doses and reached statistical significance earlier than Raw and H. Crackle recording during mechanical ventilation can be employed as a simple method with which to monitor lung recruitment-derecruitment.

Preoperative pulmonary hemodynamics determines changes in airway and tissue mechanics following surgical repair of congenital heart diseases.

To characterize the effect of changes in pulmonary hemodynamics on airway and tissue mechanics, forced oscillatory input impedance of the respiratory system (Zrs) was measured between 0.4-12 Hz in two groups of children undergoing surgical repair of congenital heart disease (CHD) immediately before sternotomy and after chest closure during short apneic intervals. Children with lesions associated with high pulmonary blood flow and/or pressure (septal defects; HP group, n = 12) and children with hypoperfused lungs (tetralogy of Fallot; LP group, n = 12) were included in the study. Airway resistance (Raw), and coefficients of respiratory tissue damping (G) and elastance (H), were estimated from Zrs by model-fitting. A postoperative reduction in pulmonary blood flow and/or pressure in the HP group resulted in an immediate decrease in Raw of 29 +/- 9 (SE)% (P < 0.05), whereas children in the LP group had increases in Raw (24 +/- 17%, no significance) after surgery. No significant change was observed in G in either the HP (6.4 +/- 13%) or LP (27 +/- 23%) group, while H increased in children of both the HP (23 +/- 8%, P < 0.05) and LP (36 +/- 7%, P < 0.01) groups. These results suggest that the preoperative pulmonary hemodynamic condition determines changes in airway mechanics: surgical repair of CHD leads to an improvement in airway function only in children with congested lungs. The adverse effects of surgery, mechanical ventilation, and/or cardiopulmonary bypass may be responsible for the increased stiffness of the respiratory system observed in both groups of children.

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.

Effects of volatile anaesthetic agents on enhanced airway tone in sensitized guinea pigs.

BACKGROUND: Although volatile anaesthetics afford protection against bronchospasm, their potential to reverse a sustained constriction of hyperreactive airways has not been characterized. Accordingly, we investigated the ability of halothane, isoflurane, sevoflurane and desflurane to reverse lung constriction induced by prolonged stimulation of the muscarinic receptors in guinea pigs sensitized to ovalbumin. METHODS: Pulmonary input impedance (ZL) was measured using forced oscillations in five groups of ovalbumin-sensitized, mechanically ventilated guinea pigs. ZL was measured under baseline conditions, during steady-state bronchoconstriction induced by an i.v. infusion of methacholine (MCh), and after administration of one of the volatile agents at 1 MAC after the induction of a steady-state bronchoconstriction. Airway resistance (Raw), and parenchymal tissue resistive and elastic coefficients were extracted from ZL by model fitting. RESULTS: All four volatile agents exhibited an initial relaxation of the MCh-induced airway constriction followed by gradual increases in Raw. The bronchodilatory effect of isoflurane was the most potent (-28.9 (SE 5.5)% at 2 min, P<0.05) and lasted longest (7 min); sevoflurane and halothane had shorter and more moderate effects (-21.1 (3.9)%, P<0.05, and -6.1 (1.7)%, P<0.05, respectively, at 1 min). Desflurane caused highly variable changes in Raw, with a tendency to enhance airway tone. CONCLUSIONS: Volatile agents can reverse sustained MCh-induced airway constriction only transiently in sensitized guinea pigs. Isoflurane proved most beneficial in temporally improving lung function in the presence of a severe constriction of allergic inflamed airways. Desflurane displayed potential to induce further airway constriction.

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.

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.

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

Hyperoxia-induced lung damage was investigated via airway and respiratory tissue mechanics measurements with low-frequency forced oscillations (LFOT) and analysis of spontaneous breathing indexes by barometric whole body plethysmography (WBP). WBP was performed in the unrestrained awake mice kept in room air (n = 12) or in 100% oxygen for 24 (n = 9), 48 (n = 8), or 60 (n = 9) h, and the indexes, including enhanced pause (Penh) and peak inspiratory and expiratory flows, were determined. The mice were then anesthetized, paralyzed, and mechanically ventilated. Airway resistance, respiratory system resistance at breathing frequency, and tissue damping and elastance were identified from the LFOT impedance data by model fitting. The monotonous decrease in airway resistance during hyperoxia correlated best with the increasing peak expiratory flow. Respiratory system resistance and tissue damping and elastance were unchanged up to 48 h of exposure but were markedly elevated at 60 h, with associated decreases in peak inspiratory flow. Penh was increased at 24 h and sharply elevated at 60 h. These results indicate no adverse effect of hyperoxia on the airway mechanics in mice, whereas marked parenchymal damage develops by 60 h. The inconsistent relationships between LFOT parameters and WBP indexes suggest that the changes in the latter reflect alterations in the breathing pattern rather than in the mechanical properties. It is concluded that, in the presence of diffuse lung disease, Penh is inadequate for characterization of the mechanical status of the respiratory system.

Protective effects of volatile agents against methacholine-induced bronchoconstriction in rats.

BACKGROUND: The protective properties of common volatile agents against generalized lung constriction have previously been addressed only via estimations of parameters that combine airway and tissue mechanics. Their effectiveness in preventing airway constriction have not been compared systematically. Therefore, the authors investigated the abilities of halothane, isoflurane, sevoflurane, and desflurane to provide protection against airway constriction induced by methacholine. METHODS: Low-frequency pulmonary impedance data were collected in open-chest rats under baseline conditions and during three consecutive intravenous infusions of methacholine (32 microg x kg(-1) x min(-1)) while the animals were anesthetized with intravenous pentobarbital (control group). Methacholine challenges were performed in four other groups of rats, first during intravenous anesthesia and then repeated during the inhalation of halothane, isoflurane, sevoflurane, or desflurane at concentrations of 1 and 2 minimum alveolar concentration (MAC). Airway resistance and inertance, parenchymal damping, and elastance were estimated from the impedance data by model fitting. RESULTS: The methacholine-induced increases in airway resistance during intravenous pentobarbital anesthesia (204 +/- 53%) were markedly and significantly (P < 0.005) reduced by 1-MAC doses of halothane (80 +/- 48%), isoflurane (112 +/- 59%), sevoflurane (68 +/- 34%), and desflurane (96 +/- 34%), with no significant difference between the gases applied. Increasing the concentration to 2 MAC did not lead to any significant further protection against the increase in airway resistance. CONCLUSIONS: These data demonstrate that isoflurane, sevoflurane, and desflurane are as effective as the widely accepted halothane in protecting against methacholine-induced airway constriction.

Methacholine responsiveness in infants assessed with low frequency forced oscillation and forced expiration techniques.

BACKGROUND: The contribution of the pulmonary tissues to the mechanical behaviour of the respiratory system is well recognised. This study was undertaken to detect airway and lung tissue responses to inhaled methacholine (Mch) using the low frequency forced oscillation technique (LFOT). METHODS: The respiratory system impedance (Zrs, 0.5-20 Hz) was determined in 17 asymptomatic infants. A model containing airway resistance (Raw) and inertance (Iaw) and a constant phase tissue damping (G) and elastance (H) was fitted to Zrs data. Tissue hysteresivity (eta) was calculated as eta=G/H. The raised volume rapid thoracic compression technique (RVRTC) was used to generate forced expiratory volume in 0.5 seconds (FEV(0.5)). Lung function was determined at baseline and following inhaled Mch in doubling doses (0.25-16 mg/ml) until the maximal dose was reached or a fall of 15% in FEV(0.5) was achieved (PC(15)FEV(0.5)). The response to Mch was defined in terms of the concentration of Mch provoking a change in lung function parameters of more than two standard deviation units (threshold concentration). RESULTS: At PC(15)FEV(0.5) a response in Raw, Iaw, G, and eta, but not H, was detected (mean (SE) 61.28 (12.22)%, 95.43 (34.31)%, 46.28 (22.36)%, 44.26 (25.83)%, and -6.48 (4.94)%, respectively). No significant differences were found between threshold concentrations of LFOT parameters and FEV(0.5). CONCLUSIONS: Inhaled Mch alters both airway and respiratory tissue mechanics in infants.

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.

Airway and respiratory tissue mechanics in normal infants.

Low-frequency respiratory impedance (Zrs) was measured by applying a forcing signal, between 0.5 and 21 Hz at a transrespiratory pressure of 20 cm H(2)O, in a cross-sectional study of 37 normal infants. A model containing an airway resistance (Raw) and inertance (Iaw) and a tissue damping (G) and elastance (H) was fitted to the individual Zrs. Forced expiratory volume in 0.5 second (FEV(0.5)) was determined using the raised volume rapid thoracic compression technique. Multivariate regression analysis was used to analyze the relationships between the lung function parameters and length. Both airway and tissue parameters showed a decreasing quadratic relationship with increasing length. FEV(0.5) showed an increasing cubic relationship with length. A family history of asthma was found to have a negative effect on Raw, H, and FEV(0.5).

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

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.