J. Tolnai

Lung volumes and respiratory mechanics in elastase-induced emphysema in mice

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.

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.

Functional and morphological assessment of early impairment of airway function in a rat model of emphysema

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.

Lung structure and function in elastase-treated rats: A follow-up study

Structural and functional longitudinal alterations of the lungs were followed in an emphysema model. Rats were treated with porcine pancreatic elastase (PPE, n=21) or saline (controls, C, n=19). Before the treatment and 3, 10, 21 and 105 days thereafter, absolute lung volumes (FRC, TLC and RV) and tissue mechanical parameters (elastance: H; damping: G) were determined. At 3, 21 and 105 days the lungs were fixed in subgroups of rats. From histological samples the equivalent diameter of airspaces (Dalv), elastin (Mec) and collagen densities were assessed. In the PPE group, FRC and RV were higher from 3 days after treatment compared to controls (p<0.001), while TLC exhibited a delayed increase. H and G decreased in the PPE group throughout the study (p<0.001). Higher Mec (p<0.001) and late-phase inflammation were observed at 105 days. We conclude that during the progression of emphysema, septal failures increase Dalv which decreases H; this reveals a strong structure-function relationship.

Estimating the diameter of airways susceptible for collapse using crackle sound

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.

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.

Volume increments and crackle sounds during lung reinflation

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.