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 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)

Variability of airway responses to inhaled histamine in normal subjects

1979 ◽  
Vol 47 (1) ◽  
pp. 51-58 ◽  
Author(s):  
M. P. Habib ◽  
P. D. Pare ◽  
L. A. Engel
Keyword(s):  
Dose Response ◽  
Lung Volume ◽  
Normal Population ◽  
Normal Subjects ◽  
Beta Blockade ◽  
Forced Expiration ◽  
Response Curves ◽  
Double Blind ◽  
Dose Response Curves ◽  
Airway Responses

Dose-response curves to inhaled histamine were studied in 12 normal subjects. Pulmonary resistance (RL) and dynamic compliance (Cdyn) were measured during tidal breathing, and maximum expiratory flow rates, at an absolute lung volume corresponding to 40% of control vital capacity, were obtained during forced expiration from tidal end inspiration (Vmax40p) and from total lung capacity (Vmax40c). Threshold was defined as the histamine dose at which a departure from the range of normal measurements was observed. RL and Vmax40p indicated lowest threshold values, which varied by a factor of 32 and 38, respectively. There was no correlation between reactivity, which reflects the slope of the dose-response curve beyond the threshold dose, and threshold doses, nor between the initial RL (normalized for lung volume) and either threshold or reactivity. In eight subjects, restudied on two occasions after 10 mg propranolol or after saline, injected in a double-blind manner, there was no change in the dose-response curves. These results indicate that different indices of bronchoconstriction may yield different dose-response curves and hence different sensitivities. In addition, a wide variation of airway responses to inhaled histamine exists in the normal population and beta-blockade does not influence this variability.

Volume dependence of airway and tissue impedances in mice

2003 ◽  
Vol 94 (4) ◽  
pp. 1460-1466 ◽  
Author(s):  
Peter D. Sly ◽  
Rachel A. Collins ◽  
Cindy Thamrin ◽  
Debra J. Turner ◽  
Zoltan Hantos
Keyword(s):  
Lung Volume ◽  
Respiratory Mechanics ◽  
Model Fitting ◽  
Tissue Mechanics ◽  
Surface Acting ◽  
Opening Pressure ◽  
Lung Volumes ◽  
Volume Dependence ◽  
Airway Opening ◽  
Tissue Matrix

We measured respiratory input impedance (1–25 Hz) in mice and obtained parameters for airway and tissue mechanics by model fitting. Lung volume was varied by inflating to airway opening pressure (Pao) between 0 and 20 cmH2O. The expected pattern of changes in respiratory mechanics with increasing lung volume was seen: a progressive fall in airway resistance and increases in the coefficients of tissue damping and elastance. A surprising pattern was seen in hysteresivity (η), with a plateau at low lung volumes (Pao < 10 cmH2O), a sharp fall occurring between 10 and 15 cmH2O, and η approaching a second (lower) plateau at higher lung volumes. Studies designed to elucidate the mechanism(s) behind this behavior revealed that this was not due to chest wall properties, differences in volume history at low lung volume, time dependence of volume recruitment, or surface-acting forces. Our data are consistent with the notion that at low lung volumes the mechanics of the tissue matrix determine η, whereas at high lung volumes the properties of individual fibers (collagen) become more important.

Age and Speech Breathing

1987 ◽  
Vol 30 (3) ◽  
pp. 351-366 ◽  
Author(s):  
Jeannette D. Hoit ◽  
Thomas J. Hixon
Keyword(s):  
Lung Volume ◽  
Respiratory Function ◽  
Vital Capacity ◽  
Age Groups ◽  
Residual Volume ◽  
Healthy Men ◽  
Breathing Disorders ◽  
Age Related ◽  
Speech Breathing ◽  
Underlying Mechanisms

Thirty healthy men representing three widely different age groups (25, 50, and 75 years) were studied with respect to general respiratory function and speech breathing. Subdivisions of the lung volume were found to differ with age and most markedly so for measures of vital capacity and residual volume. Speech breathing also was found to differ with age and was characterized by differences in lung volume excursion, rib cage volume initiation, number of syllables per breath group; and lung volume expended per syllable: Age-related differences in general respiratory function and speech breathing are discussed in relation to possible underlying mechanisms. In addition, implications are drawn regarding the evaluation and management of individuals with speech breathing disorders.

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 Effect of Bronchoscopic Lung Volume Reduction in Advanced Emphysema on Energy Balance Regulation

Respiration ◽  
2021 ◽  
pp. 1-8
Author(s):  
Karin Sanders ◽  
Karin Klooster ◽  
Lowie E.G.W. Vanfleteren ◽  
Guy Plasqui ◽  
Anne-Marie Dingemans ◽  
...  
Keyword(s):  
Energy Balance ◽  
Lung Volume ◽  
Respiratory Mechanics ◽  
Volume Reduction ◽  
Fat Free Mass ◽  
Whole Body ◽  
Energy Requirements ◽  
Lung Volume Reduction ◽  
Clinical Trial Registry ◽  
The Impact

<b><i>Background:</i></b> Hypermetabolism and muscle wasting frequently occur in patients with severe emphysema. Improving respiratory mechanics by bronchoscopic lung volume reduction (BLVR) might contribute to muscle maintenance by decreasing energy requirements and alleviating eating-related dyspnoea. <b><i>Objective:</i></b> The goal was to assess the impact of BLVR on energy balance regulation. <b><i>Design:</i></b> Twenty emphysematous subjects participated in a controlled clinical experiment before and 6 months after BLVR. Energy requirements were assessed: basal metabolic rate (BMR) by ventilated hood, total daily energy expenditure (TDEE) by doubly labelled water, whole body fat-free mass (FFM) by deuterium dilution, and physical activity by accelerometry. Oxygen saturation, breathing rate, and heart rate were monitored before, during, and after a standardized meal via pulse oximetry and dyspnoea was rated. <b><i>Results:</i></b> Sixteen patients completed follow-up, and among those, 10 patients exceeded the minimal clinically important difference of residual volume (RV) reduction. RV was reduced with median (range) 1,285 mL (−2,430, −540). Before BLVR, 90% of patients was FFM-depleted despite a normal BMI (24.3 ± 4.3 kg/m<sup>2</sup>). BMR was elevated by 130%. TDEE/BMR was 1.4 ± 0.2 despite a very low median (range) daily step count of 2,188 (739, 7,110). Following BLVR, the components of energy metabolism did not change significantly after intervention compared to before intervention, but BLVR treatment decreased meal-related dyspnoea (4.1 vs. 1.7, <i>p</i> = 0.019). <b><i>Conclusions:</i></b> Impaired respiratory mechanics in hyperinflated emphysematous patients did not explain hypermetabolism. <b><i>Clinical Trial Registry Number:</i></b> NCT02500004 at www.clinicaltrial.gov.

Effect of aging alone on mechanical properties of the normal adult human lung

1977 ◽  
Vol 43 (6) ◽  
pp. 1054-1062 ◽  
Author(s):  
R. J. Knudson ◽  
D. F. Clark ◽  
T. C. Kennedy ◽  
D. E. Knudson
Keyword(s):  
Respiratory Mechanics ◽  
Human Lung ◽  
Age Groups ◽  
The Elderly ◽  
Elastic Recoil ◽  
Lung Volumes ◽  
Men And Women ◽  
Maximum Expiratory Flow ◽  
Alpha1 Antitrypsin ◽  
Adult Human Lung

For plethysmographic studies of respiratory mechanics, we selected, from a general population, 51 subjects, aged 25–75 yr, who had never smoked, had no present or past cardiorespiratory symptoms or disease, were alpha1-antitrypsin MM phenotypes, and were normal by physical examination, vectorcardiography, and chest roentgenography. Approximately equal numbers of men and women were represented in each of three age groups; 25–35, 36–64, and 65–75. Both sexes demonstrated loss of lung elastic recoil with age, most significant at high lung volumes, but the rate of loss was less than previously reported. Males had higher lung recoil than females of comparable age, but if lung size was taken into account, there were no sex differences in bulk elastic properties. Maximum expiratory flow diminished with age only at low volumes, suggesting that equal pressure points are more centrally located at low lung volumes in the elderly.

Lung volume specificity of inspiratory muscle training

1994 ◽  
Vol 77 (2) ◽  
pp. 789-794 ◽  
Author(s):  
G. E. Tzelepis ◽  
D. L. Vega ◽  
M. E. Cohen ◽  
F. D. McCool
Keyword(s):  
Lung Volume ◽  
Vital Capacity ◽  
Inspiratory Muscle ◽  
Control Group ◽  
Residual Volume ◽  
Maximal Inspiratory Pressure ◽  
Muscle Training ◽  
Inspiratory Capacity ◽  
Lung Volumes ◽  
Before And After

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.

Development of Decreased Insulin-Induced Glucose Transport in Skeletal Muscle of Glucose-Intolerant Hybrids of Diabetic GK Rats

1995 ◽  
Vol 88 (3) ◽  
pp. 301-306 ◽  
Author(s):  
Lorraine A. Nolte ◽  
Samy M. Abdel-Halim ◽  
Iva K. Martin ◽  
Amel Guenifi ◽  
Juleen R. Zierath ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Glucose Transport ◽  
Glucose Intolerance ◽  
Dose Response ◽  
Insulin Dose ◽  
Age Groups ◽  
Plasma Free Fatty Acid ◽  
Response Curves ◽  
And Control

1. The effect of glucose intolerance on insulin-stimulated glucose transport in isolated skeletal muscles was investigated in male F, hybrids of spontaneously diabetic GK (Goto—Kakizaki) and control Wistar rats at 1 and 2 months of age. 2. Hybrid rats are characterized by markedly impaired glucose-induced insulin secretion. The area under the blood glucose curve was significantly higher following an intraperitoneal glucose injection (2 g/kg) in hybrid rats in both age groups than in the control rats (P < 0.001). In 2-month-old hybrid rats the incremental area under the insulin curve during the intraperitoneal glucose tolerance test was not different from that of control rats. Serum cholesterol, triacylglycerol or plasma free fatty acid levels did not differ between the groups. Fasting and post-prandial plasma glucose concentrations were elevated in 2-month-old hybrid rats compared with control rats (54%, P < 0.05, and 27%, P < 0.05, respectively), but were not differerent in 1-month-old rats. Plasma insulin did not differ between the hybrid and control rats in the fasting or post-prandial state at either age studied. 3. The insulin dose—response curves for 3-O-methylglucose transport did not differ between 1-month-old hybrid and control rats for either the soleus or epitrochlearis muscle. The insulin dose—response curve for the epitrochlearis, but not for the soleus, muscle from 2-month-old hybrid rats was shifted to the right compared with the curve from the control animals (P < 0.05). 4. In conclusion, the hybrid rat is a non-obese, non-hyperinsulinaemic animal model, which at a young age is characterized by impaired insulin secretion and moderate glucose intolerance. In this glucose-intolerant rat model, mild peripheral insulin resistance gradually develops, as reflected by the decreased insulin-induced glucose transport in the fast-twitch epitrochlearis muscle. It is suggested that the elevated blood glucose per se may have contributed to the slight decrease in peripheral insulin action.

Airway responses to inhaled histamine in asymptomatic smokers and nonsmokers

1977 ◽  
Vol 42 (4) ◽  
pp. 508-513 ◽  
Author(s):  
N. E. Brown ◽  
E. R. McFadden ◽  
R. H. Ingram
Keyword(s):  
Vital Capacity ◽  
Total Lung Capacity ◽  
Aerosol Deposition ◽  
Flow Volume ◽  
Maximal Flow ◽  
Airway Reactivity ◽  
Lung Capacity ◽  
Large Airway ◽  
Airway Response ◽  
Airway Responses

Bronchia reactivity to inhaled histamine was assessed in asymptomatic cigarette smokers and in nonsmoking atopic and nonatopic subjects. The only prechallenge between-group difference was the ratio of maximal flow on 80% helium-20% oxygen (Vmax HeO2) to maximal flow on air (Vmax air) from partial expiratory flow volume curves at 25% vital capacity (25% VC PEFV): Mean +/- SEM for smokers 1.18 /+- 0.06, atopics 1.45 +/- 0.08, nonatopics 1.51 +/- 0.03. This suggests that prior to inhalation to total lung capacity, the predominant site of resistance at flow limitation was in smaller airways of the smokers and in larger airways of both groups of nonsmokers. Following inhalation of histamine, smokers and nonatopics had similar changes in lung volumes and Vmax air which were less than in atopics. The Vmax HeO2/Vmax air ratios at 25% VC PEFV increased in smokers and decreased in nonsmokers: smokers 1.48 +/- 0.08, atopics 1.22 +/- 0.10, nontopics 1.16 +/- 0.06. This suggests a predominant large airway response in smokers and a prominent small airway response in nonsmokers. These responses may reflect differences in the predominant site of aerosol deposition rather than in airway reactivity.

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