Effects of elastase-induced emphysema on airway responsiveness to methacholine in rats

1989 ◽  
Vol 66 (2) ◽  
pp. 606-612 ◽  
Author(s):  
S. Bellofiore ◽  
D. H. Eidelman ◽  
P. T. Macklem ◽  
J. G. Martin
Keyword(s):  
Lung Volume ◽  
Brown Norway ◽  
Pulmonary Mechanics ◽  
Maximum Increase ◽  
Before And After ◽  
Airway Response ◽  
Residual Capacity ◽  
Airway Responses ◽  
Norway Rats ◽  
Concentration Response Curve

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)

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 ◽  
...  
Keyword(s):  
Lung Volume ◽  
Maximal Response ◽  
Maximal Effect ◽  
Response Curves ◽  
Lung Volumes ◽  
Before And After ◽  
Residual Capacity ◽  
Induced Changes ◽  
Conducting Airways ◽  
Concentration Response Curve

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.

scholarly journals Lung elastic recoil during breathing at increased lung volume

1999 ◽  
Vol 87 (4) ◽  
pp. 1491-1495 ◽  
Author(s):  
Joseph R. Rodarte ◽  
Gassan Noredin ◽  
Charles Miller ◽  
Vito Brusasco ◽  
Riccardo Pellegrino ◽  
...  
Keyword(s):  
Stress Relaxation ◽  
Tidal Volume ◽  
Lung Volume ◽  
Normal Subjects ◽  
Dynamic Hyperinflation ◽  
Airway Closure ◽  
Elastic Recoil ◽  
Volume Increase ◽  
Before And After ◽  
Residual Capacity

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.

scholarly journals Strain dependence of the airway response to dry-gas hyperpnea challenge in the rat

1999 ◽  
Vol 86 (1) ◽  
pp. 152-158 ◽  
Author(s):  
X. X. Yang ◽  
W. S. Powell ◽  
L. J. Xu ◽  
J. G. Martin
Keyword(s):  
Tidal Volume ◽  
Receptor Antagonist ◽  
Spontaneous Breathing ◽  
Brown Norway ◽  
Pulmonary Resistance ◽  
Strain Dependence ◽  
Fischer 344 ◽  
Airway Response ◽  
Airway Responses ◽  
Strain Dependent

The aim of the study was to investigate strain dependence and mechanisms of airway responses to dry-gas hyperpnea challenge in the rat. We studied responses in a strain that is hyperresponsive to methacholine, Fischer 344 (F-344); in two normoresponsive strains, Lewis and ACI; and in an atopic but normoresponsive strain, Brown Norway (BN). We examined the effects of a neurokinin (NK) 1-receptor (CP-99994), an NK2-receptor (SR-48968), and a leukotriene D4(LTD4)-receptor antagonist (pranlukast) on responses to hyperpnea challenge in BN rats. The animals were ventilated with a tidal volume of 8 ml/kg and a frequency of 150 breaths/min with either a dry or humidified mixture of 5% CO2-95% O2 for 5 min for hyperpnea challenge, whereas responses to challenge were measured during spontaneous breathing. Pulmonary resistance increased after dry-gas challenge in BN and ACI but not in F-344 and Lewis rats. CP-99994, SR-48968, and pranlukast significantly attenuated the increase in pulmonary resistance after dry-gas challenge. There were no significant differences in responsiveness to airway challenge with LTD4 among the BN, F-344 and ACI rats. We conclude that responses to dry-gas hyperpnea challenge are strain dependent in rats and are mediated by NKs and LTD4.

The Interpretation of Different Measurements of Airways Obstruction in the Presence of Lung Volume Changes in Bronchial Asthma

1978 ◽  
Vol 54 (3) ◽  
pp. 313-321
Author(s):  
K. B. Saunders ◽  
M. Rudolf
Keyword(s):  
Lung Volume ◽  
Time Course ◽  
Forced Expiratory Volume ◽  
Specific Conductance ◽  
Volume Changes ◽  
Lung Volumes ◽  
Bronchodilator Response ◽  
Before And After ◽  
Residual Capacity ◽  
Airways Resistance

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.

Comparison of upper and lower airway responses of two sensitized rat strains to inhaled antigen

1992 ◽  
Vol 73 (4) ◽  
pp. 1608-1613 ◽  
Author(s):  
L. J. Xu ◽  
S. Sapienza ◽  
T. Du ◽  
S. Waserman ◽  
J. G. Martin
Keyword(s):  
Upper Airway ◽  
Brown Norway ◽  
Lower Airway ◽  
Sprague Dawley ◽  
Pulmonary Resistance ◽  
Upper Airways ◽  
Tracheal Pressure ◽  
Airway Response ◽  
Airway Responses ◽  
Inbred Rat

The purpose of the study was to investigate the relationships between upper airways responses and pulmonary responses of two strains of highly inbred rats to inhaled antigen. To do this we measured the upper and lower airways resistance for 60 min after challenge of Brown-Norway rats (BN; n = 13) and an inbred rat strain (MF; n = 11), derived from Sprague-Dawley, with aerosolized ovalbumin (OA). Rats were actively sensitized with OA (1 mg sc) using Bordetella pertussis as an adjuvant. Two weeks later the animals were anesthetized and challenged. Tracheal pressure, esophageal pressure, and airflow were measured, from which total pulmonary resistance was partitioned into upper airway and lower pulmonary resistance (RL). The peak upper airway response to inhaled OA was similar in BN (1.89 +/- 0.66 cmH2O.ml-1.s; n = 7) and MF (2.85 +/- 0.68 cmH2O.ml-1.s; n = 6). The lower airway response to OA challenge was substantially greater in BN, and RL changed from 0.07 +/- 0.01 to 0.34 +/- 0.13 (n = 6; P < 0.05). The MF did not have any significant increase in RL after challenge; the baseline RL was 0.12 +/- 0.02 and only reached a peak value of 0.15 +/- 0.05 (n = 5; P = NS). Lower airway responsiveness of BN (n = 10) to serotonin, an important mediator early allergic airway responses, was similar to MF (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Movement of the ribs in supine humans for small and large changes in lung volume

2021 ◽  
Author(s):  
Billy L. Luu ◽  
Rhys J. McDonald ◽  
Bart Bolsterlee ◽  
Martin E. Heroux ◽  
Jane E. Butler ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Lung Volume ◽  
Chronic Obstructive ◽  
Tidal Breathing ◽  
Obstructive Pulmonary Disease ◽  
Before And After ◽  
Residual Capacity ◽  
Joint Coordinate System ◽  
Healthy Participants ◽  
Bucket Handle

An object tracking algorithm was used on computed tomography (CT) images of the thorax from six healthy participants and nine participants with chronic obstructive pulmonary disease (COPD) to describe the movement of the ribs between the static lung volumes of functional residual capacity (FRC) and total lung capacity (TLC). The continuous motion of the ribs during tidal breathing was also described using four-dimensional CT datasets from seven participants with thoracic esophageal malignancies. Rib motion was defined relative to a local joint coordinate system where rotations about the axes that predominantly affected the anteroposterior and transverse diameters of the rib cage were referred to as pump-handle and bucket-handle movements, respectively. Between TLC and FRC, pump-handle movements were 1.8 times larger in healthy participants than in participants with COPD, in line with their 1.6 times larger inspiratory capacities. However, when rib motion was normalized to the change in lung volume, pump-handle movements were similar for healthy and COPD participant groups. We found no differences in bucket-handle movements between participant groups before and after normalization. Pump-handle movement was the dominant rib motion between FRC and TLC, on average four times greater than bucket-handle movement in healthy participants. For expiratory tidal volume, pump-handle movements were 20% smaller than bucket-handle movements. When normalized to tidal volume and compared to inspiratory capacity, pump-handle movements were smaller and bucket-handle movements were larger during tidal breathing. The findings suggest that the pump-handle and bucket-handle components of rib motion vary for small and large changes in lung volume.

Antigen challenge of sensitized rats increases airway responsiveness to methacholine

1988 ◽  
Vol 65 (4) ◽  
pp. 1642-1646 ◽  
Author(s):  
S. Bellofiore ◽  
J. G. Martin
Keyword(s):  
Geometric Mean ◽  
Airway Responsiveness ◽  
Brown Norway ◽  
Base Line ◽  
Control Value ◽  
Equivalent Time ◽  
Time Period ◽  
Before And After ◽  
Experimental Group ◽  
Norway Rats

We measured airway responsiveness to methacholine (MCh) of highly inbred rats before and after six inhalational challenges with antigen. Ten Brown-Norway rats (130-216 g) that were actively sensitized to ovalbumin (OA) received six challenges with OA at 5-day intervals beginning 19 days after sensitization. An aerosol of OA (5% wt/vol) was inhaled for 1, 2, 5, and 10 min or until pulmonary resistance (RL) increased by at least 50%. Challenges with aerosolized MCh were performed immediately before and 14 days after sensitization, 2 days after the 3rd OA exposure, and 2, 7, 12, and 17 days after the 6th OA challenge. Four unsensitized rats underwent inhalational challenges with MCh over an equivalent time period. Responsiveness to MCh was calculated as the concentration of MCh required to increase RL to 200% of the control value (EC200RL). Seven out of 10 rats in the experimental group reacted to the first OA challenge with an immediate increase in RL of greater than 50% of control (range 70-550%). Three animals were unreactive to OA. Base-line EC200RL for all rats undergoing sensitization was 2.13 mg/ml (geometric mean), and it did not change significantly after sensitization (2.05 mg/ml). However, EC200RL of the rats that reacted to OA (n = 7) decreased significantly after 3 (1.11 mg/ml; P less than 0.005) and 6 OA exposures (0.96 mg/ml; P less than 0.005). The increase in responsiveness to inhaled MCh was present 17 days after the last OA exposure (EC200RL = 1.40 mg/ml; P less than 0.05). EC200RL of neither the unreactive sensitized rats (n = 3) nor the control rats (n = 4) changed after OA challenges.(ABSTRACT TRUNCATED AT 250 WORDS)

Methacholine responsiveness in mice from 2 to 8 wk of age

2007 ◽  
Vol 103 (2) ◽  
pp. 542-546 ◽  
Author(s):  
Elizabeth M. Bozanich ◽  
Tibor Z. Jánosi ◽  
Rachel A. Collins ◽  
Cindy Thamrin ◽  
Debra J. Turner ◽  
...  
Keyword(s):  
Lung Volume ◽  
Respiratory Mechanics ◽  
Age Groups ◽  
Model Fitting ◽  
Residual Volume ◽  
Response Curves ◽  
Asthma Phenotype ◽  
Adult Mice ◽  
Airway Response ◽  
Airway Responses

Many chronic human lung diseases have their origin in early childhood, yet most murine models used to study them utilize adult mice. An important component of the asthma phenotype is exaggerated airway responses, frequently modelled by methacholine (MCh) challenge. The present study was undertaken to characterize MCh responses in mice from 2 to 8 wk of age measuring absolute lung volume and volume-corrected respiratory mechanics as outcome variables. Female BALB/c mice aged 2, 3, 4, 6, and 8 wk were studied during cumulative intravenous MCh challenge. Following each MCh dose, absolute lung volume was measured plethysmographically at functional residual volume and during a slow inflation to 20-hPa transrespiratory pressure. Respiratory system impedance was measured continuously during the inflation maneuver and partitioned into airway and constant-phase parenchymal components by model fitting. Volume-corrected (specific) estimates of respiratory mechanics were calculated. Intravenous MCh challenge induced a predominantly airway response with no evidence of airway closure in any age group. No changes in functional residual volume were seen in mice of any age during the MCh challenge. The specific airway resistance MCh dose response curves did not show significant differences between the age groups. The results from the present study do not show systematic differences in MCh responsiveness in mice from 2 to 8 wk of age.

Effects of abdominal opening on respiratory system mechanics in ventilated rats

1989 ◽  
Vol 66 (6) ◽  
pp. 2496-2501 ◽  
Author(s):  
W. A. Zin ◽  
M. A. Martins ◽  
P. R. Silva ◽  
R. S. Sakae ◽  
A. L. Carvalho ◽  
...  
Keyword(s):  
Respiratory System ◽  
Lung Volume ◽  
Open Abdomen ◽  
Rib Cage ◽  
Mechanically Ventilated ◽  
Respiratory System Mechanics ◽  
Before And After ◽  
Residual Capacity ◽  
The Difference ◽  
Lateral Diameter

In 16 anesthetized paralyzed mechanically ventilated rats, respiratory system mechanics and rib cage dimensions were determined both before and after wide abdominal opening. In eight animals the end-inflation occlusion method disclosed statistically significant postoperative increases in respiratory system elastance (from 4.84 to 6.49 cmH2O.ml-1) and resistance (from 0.224 to 0.300 cmH2O.ml-1.s); the latter resulted from a rise of its uneven component (from 0.161 to 0.209 cmH2O.ml-1.s). In the remaining rats, rib cage morphometry at functional residual capacity after surgery showed significant decreases in lower rib cage circumference and anteroposterior and lateral diameters, whereas there was an increase in upper rib cage circumference and a fall in its lateral diameter. When these parameters were measured at end-inspiratory lung volume, the difference between intact and open abdomen were less striking; only lower rib cage circumference and upper rib cage lateral diameter significantly decreased postoperatively. Because surgery induced an expiratory volume of only 0.1 ml, it can be concluded that abdominal opening redistributed regional volumes within the lung, leading to increased unevenness in the system.

Effects of bemiparin on airway responses to antigen in sensitized Brown–Norway rats

2005 ◽  
Vol 507 (1-3) ◽  
pp. 261-271 ◽  
Author(s):  
Jana Suchankova ◽  
Manuel Mata ◽  
Julio Cortijo ◽  
Esteban J. Morcillo
Keyword(s):  
Brown Norway ◽  
Airway Responses ◽  
Norway Rats
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