Methacholine-induced bronchoconstriction in dogs: effects of lung volume and O3 exposure

1988 ◽  
Vol 65 (6) ◽  
pp. 2679-2686 ◽  
Author(s):  
S. T. Kariya ◽  
S. A. Shore ◽  
W. A. Skornik ◽  
K. Anderson ◽  
R. H. Ingram ◽  
...  

The maximal effect induced by methacholine (MCh) aerosols on pulmonary resistance (RL), and the effects of altering lung volume and O3 exposure on these induced changes in RL, was studied in five anesthetized and paralyzed dogs. RL was measured at functional residual capacity (FRC), and lung volumes above and below FRC, after exposure to MCh aerosols generated from solutions of 0.1-300 mg MCh/ml. The relative site of response was examined by magnifying parenchymal [RL with large tidal volume (VT) at fast frequency (RLLS)] or airway effects [RL with small VT at fast frequency (RLSF)]. Measurements were performed on dogs before and after 2 h of exposure to 3 ppm O3. MCh concentration-response curves for both RLLS and RLSF were sigmoid shaped. Alterations in mean lung volume did not alter RLLS; however, RLSF was larger below FRC than at higher lung volumes. Although O3 exposure resulted in small leftward shifts of the concentration-response curve for RLLS, the airway dominated index of RL (RLSF) was not altered by O3 exposure, nor was the maximal response using either index of RL. These data suggest O3 exposure does not affect MCh responses in conducting airways; rather, it affects responses of peripheral contractile elements to MCh, without changing their maximal response.

1989 ◽  
Vol 66 (2) ◽  
pp. 606-612 ◽  
Author(s):  
S. Bellofiore ◽  
D. H. Eidelman ◽  
P. T. Macklem ◽  
J. G. Martin

We examined the effects of elastase-induced emphysema on lung volumes, pulmonary mechanics, and airway responses to inhaled methacholine (MCh) of nine male Brown Norway rats. Measurements were made before and weekly for 4 wk after elastase in five rats. In four rats measurements were made before and at 3 wk after elastase; in these same animals the effects of changes in end-expiratory lung volume on the airway responses to MCh were evaluated before and after elastase. Airway responses were determined from peak pulmonary resistance (RL) calculated after 30-s aerosolizations of saline and doubling concentrations of MCh from 1 to 64 mg/ml. Porcine pancreatic elastase (1 IU/g) was administered intratracheally. Before elastase RL rose from 0.20 +/- 0.02 cmH2O.ml-1.s (mean +/- SE; n = 9) to 0.57 +/- 0.06 after MCh (64 mg/ml). A plateau was observed in the concentration-response curve. Static compliance and the maximum increase in RL (delta RL64) were significantly correlated (r = 0.799, P less than 0.01). Three weeks after elastase the maximal airway response to MCh was enhanced and no plateau was observed; delta RL64 was 0.78 +/- 0.07 cmH2O.ml-1.s, significantly higher than control delta RL64 (0.36 +/- 0.7, P less than 0.05). Before elastase, increase of end-expiratory lung volume to functional residual capacity + 1.56 ml (+/- 0.08 ml) significantly reduced RL at 64 mg MCh/ml from 0.62 +/- 0.05 cmH2O.ml-1.s to 0.50 +/- 0.03, P less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)


1978 ◽  
Vol 54 (3) ◽  
pp. 313-321
Author(s):  
K. B. Saunders ◽  
M. Rudolf

1. We measured changes in peak expiratory flow rate (PEFR), forced expiratory volume in 1 s (FEV1·0), airways resistance (Raw), specific conductance (sGaw), residual volume (RV), functional residual capacity (FRC) and total lung capacity (TLC) in 44 patients with asthma. 2. When asthma was induced by exercise in five patients there were large changes in volumes, but these did not obscure changes in PEFR, which adequately defined the time course of the response. 3. In 70 comparisons before and after inhalation of bronchodilator drug in 33 asthmatic subjects, the responses were classified by the size of the change in lung volumes, which showed a concordant improvement, or no change, in 61 comparisons. Despite these lung volume changes, measurement of both PEFR and FEV1·0, would have detected a bronchodilator response in all but two cases. 4. In 81 comparisons in 23 subjects over time intervals varying from 1 day to 11 months, lung volumes changed in concordance with PEFR and FEV1·0 in 59. In eight of these comparisons, measurement of lung volumes would have altered our interpretation of the changes in PEFR and FEV1·0. 5. In the same 81 comparisons changes in airways resistance were concordant with changes in PEFR and FEV1·0 on 44 occasions, with minor discordant changes in 19. We could not explain the remaining 18 cases showing major discordance between these two types of measurement of airway calibre. 6. We conclude that both FEV1·0, and PEFR should be used for detection of a bronchodilator response, and that measurement of lung volumes will rarely contribute to the interpretation. Over longer periods, lung volumes should be measured if possible. We found no practical use for routine measurement of airways resistance in patients with asthma.


1988 ◽  
Vol 64 (1) ◽  
pp. 360-366 ◽  
Author(s):  
P. D. Sly ◽  
K. A. Brown ◽  
J. H. Bates ◽  
P. T. Macklem ◽  
J. Milic-Emili ◽  
...  

To examine the effects of changes in lung volume on the magnitude of maximal bronchoconstriction, seven anesthetized, paralyzed, tracheostomized cats were challenged with aerosolized methacholine (MCh) and respiratory system resistance (Rss) was measured at different lung volumes using the interrupter technique. Analysis of the pressure changes following end-inspiratory interruptions allowed us to partition Rss into two quantities with the units of resistance, one (Rinit) corresponding to the resistance of the airways and the other (Rdif) reflecting the viscoelastic properties of the tissues of the respiratory system as well as gas redistribution following interruption of flow. Rinit and Rdif were used to construct concentration-response curves to MCh. Lung volume was increased by the application of 5, 10, and 15 cmH2O of positive end-expiratory pressure. The curve for Rinit reached a plateau in all cats, demonstrating a limit to the degree of MCh-induced bronchoconstriction. The mean value of Rinit (cmH2O.ml-1.s) for the group under control conditions was 0.011 and rose to 0.058 after maximal bronchoconstriction; the volume at which the flow was interrupted was 11.5 +/- 0.5 (SE) ml/kg above functional residual capacity (FRC). It then fell progressively to 0.029 at 21.2 +/- 0.8 ml/kg above FRC, 0.007 at 35.9 +/- 1.3 ml/kg above FRC, and 0.005 at 52.0 +/- 1.8 ml/kg above FRC. Cutting either the sympathetic or parasympathetic branches of the vagi had no significant effect on the lung volume-induced changes in MCh-induced bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)


2019 ◽  
Vol 126 (1) ◽  
pp. 183-192 ◽  
Author(s):  
Paul J. C. Hughes ◽  
Laurie Smith ◽  
Ho-Fung Chan ◽  
Bilal A. Tahir ◽  
Graham Norquay ◽  
...  

In this study, the effect of lung volume on quantitative measures of lung ventilation was investigated using MRI with hyperpolarized 3He and 129Xe. Six volunteers were imaged with hyperpolarized 3He at five different lung volumes [residual volume (RV), RV + 1 liter (1L), functional residual capacity (FRC), FRC + 1L, and total lung capacity (TLC)], and three were also imaged with hyperpolarized 129Xe. Imaging at each of the lung volumes was repeated twice on the same day with corresponding 1H lung anatomical images. Percent lung ventilated volume (%VV) and variation of signal intensity [heterogeneity score (Hscore)] were evaluated. Increased ventilation heterogeneity, quantified by reduced %VV and increased Hscore, was observed at lower lung volumes with the least ventilation heterogeneity observed at TLC. For 3He MRI data, the coefficient of variation of %VV was <1.5% and <5.5% for Hscore at all lung volumes, while for 129Xe data the values were 4 and 10%, respectively. Generally, %VV generated from 129Xe images was lower than that seen from 3He images. The good repeatability of 3He %VV found here supports prior publications showing that percent lung-ventilated volume is a robust method for assessing global lung ventilation. The greater ventilation heterogeneity observed at lower lung volumes indicates that there may be partial airway closure in healthy lungs and that lung volume should be carefully considered for reliable longitudinal measurements of %VV and Hscore. The results suggest that imaging patients at different lung volumes may help to elucidate obstructive disease pathophysiology and progression. NEW & NOTEWORTHY We present repeatability data of quantitative metrics of lung function derived from hyperpolarized helium-3, xenon-129, and proton anatomical images acquired at five lung volumes in volunteers. Increased regional ventilation heterogeneity at lower lung inflation levels was observed in the lungs of healthy volunteers.


1994 ◽  
Vol 77 (2) ◽  
pp. 789-794 ◽  
Author(s):  
G. E. Tzelepis ◽  
D. L. Vega ◽  
M. E. Cohen ◽  
F. D. McCool

We examined the extent to which training-related increases of inspiratory muscle (IM) strength are limited to the lung volume (VL) at which the training occurs. IM strength training consisted of performing repeated static maximum inspiratory maneuvers. Three groups of normal volunteers performed these maneuvers at one of three lung volumes: residual volume (RV), relaxation volume (Vrel), or Vrel plus one-half of inspiratory capacity (Vrel + 1/2IC). A control group did not train. We constructed maximal inspiratory pressure-VL curves before and after a 6-wk training period. For each group, we found that the greatest improvements in strength occurred at the volume at which the subjects trained and were significantly greater for those who trained at low (36% for RV and 26% for Vrel) than at high volumes (13% for Vrel + 1/2IC). Smaller increments in strength were noted at volumes adjacent to the training volume. The range of vital capacity (VC) over which strength was increased was greater for those who trained at low (70% of VC) than at high VL (20% of VC). We conclude that the greatest improvements in IM strength are specific to the VL at which training occurs. However, the increase in strength, as well as the range of volume over which strength is increased, is greater for those who trained at the lower VL.


1999 ◽  
Vol 87 (4) ◽  
pp. 1491-1495 ◽  
Author(s):  
Joseph R. Rodarte ◽  
Gassan Noredin ◽  
Charles Miller ◽  
Vito Brusasco ◽  
Riccardo Pellegrino ◽  
...  

During dynamic hyperinflation with induced bronchoconstriction, there is a reduction in lung elastic recoil at constant lung volume (R. Pellegrino, O. Wilson, G. Jenouri, and J. R. Rodarte. J. Appl. Physiol. 81: 964–975, 1996). In the present study, lung elastic recoil at control end inspiration was measured in normal subjects in a volume displacement plethysmograph before and after voluntary increases in mean lung volume, which were achieved by one tidal volume increase in functional residual capacity (FRC) with constant tidal volume and by doubling tidal volume with constant FRC. Lung elastic recoil at control end inspiration was significantly decreased by ∼10% within four breaths of increasing FRC. When tidal volume was doubled, the decrease in computed lung recoil at control end inspiration was not significant. Because voluntary increases of lung volume should not produce airway closure, we conclude that stress relaxation was responsible for the decrease in lung recoil.


1998 ◽  
Vol 84 (5) ◽  
pp. 1639-1645 ◽  
Author(s):  
Maurice Beaumont ◽  
Redouane Fodil ◽  
Daniel Isabey ◽  
Frédéric Lofaso ◽  
Dominique Touchard ◽  
...  

We measured upper airway caliber and lung volumes in six normal subjects in the sitting and supine positions during 20-s periods in normogravity, hypergravity [1.8 + head-to-foot acceleration (Gz)], and microgravity (∼0 Gz) induced by parabolic flights. Airway caliber and lung volumes were inferred by the acoustic reflection method and inductance plethysmography, respectively. In subjects in the sitting position, an increase in gravity from 0 to 1.8 +Gz was associated with increases in the calibers of the retrobasitongue and palatopharyngeal regions (+20 and +30%, respectively) and with a concomitant 0.5-liter increase in end-expiratory lung volume (functional residual capacity, FRC). In subjects in the supine position, no changes in the areas of these regions were observed, despite significant decreases in FRC from microgravity to normogravity (−0.6 liter) and from microgravity to hypergravity (−0.5 liter). Laryngeal narrowing also occurred in both positions (about −15%) when gravity increased from 0 to 1.8 +Gz. We concluded that variation in lung volume is insufficient to explain all upper airway caliber variation but that direct gravity effects on tissues surrounding the upper airway should be taken into account.


1994 ◽  
Vol 77 (3) ◽  
pp. 1562-1564 ◽  
Author(s):  
Y. Sivan ◽  
J. Hammer ◽  
C. J. Newth

Studies on human infants suggested that thoracic gas volume (TGV) measured at end exhalation may not depict the true TGV and may differ from TGV measured from a series of higher lung volumes and corrected for the volume added. This was explained by gas trapping. If true, we should expect the discrepancy to be more pronounced when functional residual capacity (FRC) and higher lung volumes are measured by gas dilution techniques. We studied lung volumes above FRC by the nitrogen washout technique in 12 spontaneously breathing rhesus monkeys (5.0–11.3 kg wt; 42 compared measurements). Lung volumes directly measured were compared with preset lung volumes achieved by artificial inflation of the lungs above FRC with known volumes of air (100–260 ml). Measured lung volume strongly correlated with and was not significantly different from present lung volume (P = 0.05; r = 0.996). The difference between measured and preset lung volume was 0–5% in 41 of 42 cases [1 +/- 0.4% (SE)]. The direction of the difference was unpredictable; in 22 of 42 cases the measured volume was larger than the preset volume, but in 17 of 42 cases it was smaller. The difference was not affected by the volume of gas artificially inflated into the lungs. We conclude that, overall, lung volumes above FRC can be reliably measured by the nitrogen washout technique and that FRC measurements by this method reasonably reflect true FRC.


1995 ◽  
Vol 78 (5) ◽  
pp. 1993-1997 ◽  
Author(s):  
J. Hammer ◽  
C. J. Newth

The rapid thoracoabdominal compression (RTC) technique is commonly used in pulmonary function laboratories to assess flow-volume relationships in infants unable to produce a voluntary forced expiration maneuver. This technique produces forced expiratory flows over only a small lung volume segment (i.e., tidal volume). It has been argued that the RTC technique should be modified to measure flow-volume relationships over a larger portion of the vital capacity range to imitate the voluntary maximal forced expiratory maneuver obtained in older children and adults. We examined the effect of volume history on forced expiratory flows by generating forced expiratory flow-volume curves by RTC from well-defined inspiratory volumes delineated by inspiratory pressures of 10, 20, 30, and 40 cmH2O down to residual volume (i.e., the reference volume) in seven intubated and anesthetized infants with normal lungs [age 8.0 +/- 2.0 (SE) mo, weight 6.7 +/- 0.6 kg]. We compared maximal expiratory flows at isovolume points (25 and 10% of forced vital capacity) and found no significant differences in maximal isovolume flow rates measured from the different lung volumes. We conclude that there is no obvious need to initiate RTC from higher lung volumes if the technique is used for flow comparisons. However, compared with measurements of maximal flows at functional residual capacity by RTC from end-tidal inspiration, the initiation of RTC from a defined and reproducible inspiratory level appears to decrease the intrasubject variability of the maximal expiratory flows at low lung volumes.


1995 ◽  
Vol 78 (3) ◽  
pp. 875-880 ◽  
Author(s):  
Z. Balassy ◽  
M. Mishima ◽  
J. H. Bates

We measured the effect of lung volume on the time course of regional lung input impedance (ZA) after bolus intravenous administration of 2 mg of histamine in seven open-chest dogs using alveolar capsule oscillators. ZA (24–200 Hz) was obtained during apnea at constant lung volume every 2 s for 80 s at lung inflation pressures of 0.1, 0.2, 0.3, 0.5, 0.7, and 1.0 kPa. Local airway resistance (RA) and elastance of the local lung region were calculated by fitting a four-parameter model to the measured ZA. Total lung resistance and lung elastance were also calculated from tracheal pressure and flow measured during mechanical ventilation (0.3 Hz) just before and after each set of ZA measurements. We found the histamine-induced changes in both lung resistance and lung elastance to decrease with increasing lung volume. RA also showed a large negative dependency on lung volume, and the variation between different RA measurements became markedly increased as lung volume decreased. In contrast, local airway elastance was essentially unaffected by lung volume. These results support the idea that parenchymal tethering of the very distal airways impedes their narrowing during bronchoconstriction. They also indicate that reduced parenchymal tethering causes airway narrowing to become markedly more inhomogeneous.


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