[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate airway structure-function relations in elastase-induced emphysema in rats. Sprague-Dawley rats were treated intratracheally with 50 IU porcine pancreatic elastase (PPE, n = 8) or saline (controls, n = 6). Six weeks later, lung volumes [functional residual capacity (FRC), residual volume (RV), and total lung capacity (TLC)] and low-frequency impedance parameters (Newtonian resistance, R(N); tissue damping; tissue elastance, H) were measured, and tracheal sounds were recorded during slow inflation to TLC following in vivo degassing. The lungs were fixed and stained for standard morphometry, elastin, and collagen. In the PPE group, FRC and RV were higher [4.53 ± 0.7 (SD) vs. 3.28 ± 0.45 ml; P = 0.003 and 1.06 ± 0.35 vs. 0.69 ± 0.18 ml; P = 0.036, respectively], and H was smaller in the PPE-treated rats than in the controls (1,344 ± 216 vs. 2,178 ± 305 cmH(2)O/l; P < 0.001), whereas there was no difference in R(N). The average number of crackles per inflation was similar in the two groups; however, the crackle size distributions were different and the lower knee of the pressure-volume curves was higher in the PPE group. Microscopic images revealed different alveolar size distributions but similar bronchial diameters in the two groups. The treatment caused a slight but significant decrease in the numbers of alveolar attachments, no difference in elastin and slightly increased mean level and heterogeneity of collagen in the bronchial walls. These results suggest that tissue destruction did not affect the conventionally assessed airway resistance in this emphysema model, whereas the alterations in the recruitment dynamics can be an early manifestation of impaired airway function.
[Show abstract][Hide abstract] ABSTRACT: Airways that collapse during deflation generate a crackle sound when they reopen during subsequent reinflation. Since each crackle is associated with the reopening of a collapsed airway, the likelihood of an airway to be a crackle source is identical to its vulnerability to collapse. To investigate this vulnerability of airways to collapse, crackles were recorded during the first inflation of six excised rabbit lungs from the collapsed state, and subsequent reinflations from 5, 2, 1, and 0 cmH(2)O end-expiratory pressure levels. We derived a relationship between the amplitude of a crackle sound at the trachea and the generation number (n) of the source airway where the crackle was generated. Using an asymmetrical tree model of the rabbit airways with elastic walls, airway vulnerability to collapse was also determined in terms of airway diameter D. During the reinflation from end-expiratory pressure = 0 cmH(2)O, the most vulnerable airways were estimated to be centered at n = 12 with a peak. Vulnerability in terms of D ranged between 0.1 and 1.3 mm, with a peak at 0.3 mm. During the inflation from the collapsed state, however, vulnerability was much less localized to a particular n or D, with maximum values of n = 8 and D = 0.75 mm. Numerical simulations using a tree model that incorporates airway opening and closing support these conclusions. Thus our results indicate that there are airways of a given range of diameters that can become unstable during deflation and vulnerable to collapse and subsequent injury.
[Show abstract][Hide abstract] ABSTRACT: Absolute lung volumes such as functional residual capacity, residual volume (RV), and total lung capacity (TLC) are used to characterize emphysema in patients, whereas in animal models of emphysema, the mechanical parameters are invariably obtained as a function of transrespiratory pressure (Prs). The aim of the present study was to establish a link between the mechanical parameters including tissue elastance (H) and airway resistance (Raw), and thoracic gas volume (TGV) in addition to Prs in a mouse model of emphysema. Using low-frequency forced oscillations during slow deep inflation, we tracked H and Raw as functions of TGV and Prs in normal mice and mice treated with porcine pancreatic elastase. The presence of emphysema was confirmed by morphometric analysis of histological slices. The treatment resulted in an increase in TGV by 51 and 44% and a decrease in H by 57 and 27%, respectively, at 0 and 20 cmH(2)O of Prs. The Raw did not differ between the groups at any value of Prs, but it was significantly higher in the treated mice at comparable TGV values. In further groups of mice, tracheal sounds were recorded during inflations from RV to TLC. All lung volumes but RV were significantly elevated in the treated mice, whereas the numbers and size distributions of inspiratory crackles were not different, suggesting that the airways were not affected by the elastase treatment. These findings emphasize the importance of absolute lung volumes and indicate that tissue destruction was not associated with airway dysfunction in this mouse model of emphysema.
[Show abstract][Hide abstract] ABSTRACT: 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.
European Respiratory Journal 05/2006; 27(4):808-16. DOI:10.1183/09031936.06.00105005 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Applied Physiology 12/2000; 89(5):2030-40. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics 11/1999; 60(4 Pt B):4659-63. DOI:10.1109/IEMBS.1999.802437 · 2.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lung sounds and central airway flow were recorded during the slow
reinflation of isolated dog lung lobes. The flow transients coincided
with crackles or their bursts, which were rare and powerful before the
mass recruitment of airspaces, but became more frequent and attenuated
as the reopenings moved towards the periphery
BMES/EMBS Conference, 1999. Proceedings of the First Joint; 02/1999
[Show abstract][Hide abstract] ABSTRACT: 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).
Journal of Applied Physiology 12/1997; 83(5):1595-601. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A kutatás célja a pulmonális légutak záródási és újranyílási eseményeinek tanulmányozása, és az ezt kísérő hangjelenségek (crackle) és a tüdő mechanikai változásai közötti kapcsolat vizsgálata volt. Izolált kutya-, nyúl-, patkány- és egértüdők reinflációja közben mért crackle aktivitás analízisével feltártuk a légutak kinyílásának lavinaszerű dinamikáját és a tüdő nyomás-térfogat görbéjének kialakulásában játszott szerepét, valamint az akusztikai adatokból származtatott hörgőméretek és a hagyományos morfometria közötti egyezést. A crackle intenzitás eloszlásainak tanulmányozása a nagyobb kollapszushajlamú hörgőgenerációk identifikálásában is segítenek. In vivo kísérletekben a kilégzésvégi nyomás és a bronchokonstriktor dózis hatását a reinflációs hangesemények érzékenyebben mutatták ki, mint a légutak és a tüdőszövet mechanikai tulajdonságainak változásai. | The research was aimed at the dynamics of the closure and reopening of pulmonary airways, and the relationships between the accompanying acoustic events (crackles) and the changes in the mechanical properties of the lungs. Analysis of crackles recorded in isolated dog, rabbit, rat and mouse lungs revealed the avalanche dynamics of the airway reopening and its contribution to the development of the pulmonary pressure-volume characteristics. The dimensions of the bifurcating airways, as inferred from the distributions of the crackle intensity, agreed well with the conventional morphometric data; additionally, these distributions may help identify the bronchial generations most vulnerable to airway collapse. Results from in vivo experiments demonstrated that the changes in crackle intensity with decreasing end-expiratory pressure and increasing bronchoconstrictor dose were a more sensitive indicator of airway closure than the alterations in the global mechanical properties of the airways and lung tissues.
[Show abstract][Hide abstract] ABSTRACT: A lezárt kutatási tervben ezért kimutattuk a - klinikai gyakorlatban alkalmazott altatógázok közelítően hasonló potenciálját a bronchokonstrikció visszafordításában. - az antikolinerg szerek metakolinnal, az antihisztaminok endogén vagy exogén hisztaminnal, míg a szteroidok az antigén/antitest reakciókkal szembeni hatékonyságát a légzésfunkció romlásában. - mivacurium és a succinylcholin endogén konstriktor mediátorokat felszabadító potenciáljára, mely a légzésfunkció jelentős romlását eredményezhetik légúti hiperreaktivitás kórképében. - fiziológiás pulmonális kapilláris hemodinamika fontos, stabilizáló szerepére a fiziológiás tüdőmechanika fenntartásában. - módszertani fejlesztések fontosságát a légúti és szöveti paraméterek mérésének nem-invazív továbbfejlesztésére, valamint a funkcionális tüdőtérfogat mérésének és a légúti kinyílások által generált ún. crackle hangok analízisének jelentőségét. - kombinált endothelin-1 receptor antagonizmus jótékony hatását a hyperoxia káros hatásaival szemben a tüdőben. - pulmonális keringést helyreállító műtét hatékonyságát a légzésfunkció javításában elárasztott tüdejű gyermekekben. Kutatási eredményeink a légúti és a szöveti változások egzakt mérésével hozzájárulhatnak az aneszteziológiai gyakorlatban előforduló konstrikciós állapotok alaposabb megértéséhez. A háttérmechanizmusok feltárása hozzájárulhat a pulmonális kóros folyamatok célzott kezeléséhez. | The results of this completed research project revealed - the potential of common volatile agents to reverse bronchospasm with no difference among them. - that anticholinergics prevent methacholine-induced constriction, antihistamines are effective against endogen histamine liberation, while steroids protect the adverse effects of antigen/antibody reactions in the lungs. - the potential of mivacurium and succinylcholine in the endogenous release of constrictor agonists leading to enhanced deterioration of lung function. - the role of the filled pulmonary capillaries in the maintenance of the normal lung mechanics via stabilizing the alveolar architecture. - the importance of non-invasive lung mechanical measurements, the combination of forced oscillation technique with measurements of lung volume and crackle sounds generated by airway reopenings. - the beneficial role of a dual endothelin-1 antagonist to prevent the adverse changes in the lungs following oxygen toxicity. - that surgical repair of congenital heart diseases leads to an improvement in airway function only in children with congested lungs. These findings contributed to the understanding of the mechanisms involved during induced lung constriction or altered pulmonary haemodynamics encountered during anaesthetic management. Understanding the mechanical changes in the airways and the parenchyma separately allows a better oriented prevention and treatment of lung constriction.