Tracheal microenvironment, ANP metabolism and airway tone

In healthy individuals, a DI can reverse (bronchodilation) or prevent (bronchoprotection) induced airway constriction. For individuals with asthma or COPD, these effects may be attenuated or absent. Previous work showed that the size and duration of a DI affected the subsequent response of the airways. Also, increased airway tone lead to increased airway size variability. The present study examined how a DI affected the temporal variability in individual airway baseline size and after methacholine challenge in dogs using High-Resolution Computed Tomography. Dogs were anesthetized and ventilated, and on 4 separate days, HRCT scans were acquired before and after a DI at baseline and during a continuous intravenous infusion of methacholine (Mch) at 3 dose rates (17, 67, and 200 μg/mm). The Coefficient of Variation was used as an index of temporal variability in airway size. We found that at baseline and the lowest dose of Mch, variability decreased immediately and 5 minutes after the DI ( P < 0.0001). In contrast, with higher doses of Mch, the DI caused a variable response. At a rate of 67 μg/min of Mch, the temporal variability increased after 5 minutes, while at a rate of 200 μg/min of Mch, the temporal variability increased immediately after the DI. Increased airway temporal variability has been shown to be associated with asthma. Although the mechanisms underlying this temporal variability are poorly understood, the beneficial effects of a DI to decrease airway temporal variability was eliminated when airway tone was increased. If this effect is absent in asthmatics, this may suggest a possible mechanism for the loss of bronchoprotective and bronchodilatory effects after a DI in asthma.

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Ventilatory and occlusion pressure responses to helium breathing

Journal of Applied Physiology ◽

10.1152/jappl.1983.54.6.1525 ◽

1983 ◽

Vol 54 (6) ◽

pp. 1525-1531 ◽

Cited By ~ 24

Author(s):

E. L. DeWeese ◽

T. Y. Sullivan ◽

P. L. Yu

Keyword(s):

Breathing Circuit ◽

Minute Ventilation ◽

Normal Subjects ◽

Mouth Pressure ◽

Partial Pressure Of Co2 ◽

Lung Resistance ◽

Balloon Technique ◽

Resistive Loads ◽

End Tidal ◽

Airway Tone

To characterize the ventilatory response to resistive unloading, we studied the effect of breathing 79.1% helium-20.9% oxygen (He-O2) on ventilation and on mouth pressure measured during the first 100 ms of an occluded inspiration (P100) in normal subjects at rest. The breathing circuit was designed so that external resistive loads during both He-O2 and air breathing were similar. Lung resistance, measured in three subjects with an esophageal balloon technique, was reduced by 23 +/- 8% when breathing He-O2. Minute ventilation, tidal volume, respiratory frequency, end-tidal partial pressure of CO2, inspiratory and expiratory durations, and mean inspiratory flow were not significantly different when air was replaced by He-O2. P100, however, was significantly less during He-O2 breathing. We conclude that internal resistive unloading by He-O2 breathing reduces the neuromuscular output required to maintain constant ventilation. Unlike studies involving inhaled bronchodilators, this technique affords a method by which unloading can be examined independent of changes in airway tone.

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Protective role of epithelium in the guinea pig airway

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.4.1547 ◽

1989 ◽

Vol 66 (4) ◽

pp. 1547-1552 ◽

Cited By ~ 68

Author(s):

M. Munakata ◽

I. Huang ◽

W. Mitzner ◽

H. Menkes

Keyword(s):

Guinea Pig ◽

Protective Role ◽

Airway Epithelial ◽

Serosal Side ◽

Epithelial Surface ◽

Airway Responses ◽

Airway Tone ◽

Stimulation Of

We developed an in vitro system to assess the role of the epithelium in regulating airway tone using the intact guinea pig trachea (J. Appl. Physiol. 64: 466–471, 1988). This method allows us to study the response of the airway when its inner epithelial surface or its outer serosal surface is stimulated independently. Using this system we evaluated how the presence of intact epithelium can affect pharmacological responsiveness. We first examined responses of tracheae with intact epithelium to histamine, acetylcholine, and hypertonic KCl when stimulated from the epithelial or serosal side. We then examined the effect of epithelial denudation on the responses to these agonists. With an intact epithelium, stimulation of the inner epithelial side always caused significantly smaller changes in diameter than stimulation of the outer serosal side. After mechanical denudation of the epithelium, these differences were almost completely abolished. In the absence of intact epithelium, the trachea was 35-fold more sensitive to histamine and 115-fold more sensitive to acetylcholine when these agents were applied to the inner epithelial side. In addition, the presence of an intact epithelium almost completely inhibited any response to epithelial side challenge with hypertonic KCl. These results indicate that the airway epithelial layer has a potent protective role in airway responses to luminal side stimuli, leading us to speculate that changes in airway reactivity measured in various conditions including asthma may result in part from changes in epithelial function.

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Glucocorticoid decreases airway tone via a nongenomic pathway

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2012.05.008 ◽

2012 ◽

Vol 183 (1) ◽

pp. 10-14 ◽

Cited By ~ 7

Author(s):

Chen Wang ◽

Yi-Jia Li ◽

Yi-Qing Zheng ◽

Bing Feng ◽

Yan Liu ◽

...

Keyword(s):

Airway Tone ◽

Nongenomic Pathway

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Humoral Control of Airway Tone

Asthma ◽

10.1016/b978-012079027-2/50105-2 ◽

1998 ◽

pp. 409-421

Author(s):

Neil C. Thomson

Keyword(s):

Airway Tone ◽

Humoral Control

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Influence of the ventral surface of the medulla on tracheal responses to CO2

Journal of Applied Physiology ◽

10.1152/jappl.1986.61.3.1091 ◽

1986 ◽

Vol 61 (3) ◽

pp. 1091-1097 ◽

Cited By ~ 19

Author(s):

E. C. Deal ◽

M. A. Haxhiu ◽

M. P. Norcia ◽

J. Mitra ◽

N. S. Cherniack

Keyword(s):

Motor Activity ◽

Phrenic Nerve ◽

Ventral Surface ◽

Intermediate Area ◽

Tracheal Pressure ◽

Cervical Trachea ◽

Airway Responses ◽

Airway Tone ◽

Pressure Changes ◽

Nerve Discharge

These studies investigated the role of the intermediate area of the ventral surface of the medulla (VMS) in the tracheal constriction produced by hypercapnia. Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. Airway responses were assessed from pressure changes in a bypassed segment of the rostral cervical trachea. Hyperoxic hypercapnia increased tracheal pressure and phrenic nerve activity. Intravenous atropine pretreatment or vagotomy abolished the changes in tracheal pressure without affecting phrenic nerve discharge. Rapid cooling of the intermediate area reversed the tracheal constriction produced by hypercapnia. Graded cooling produced a progressive reduction in the changes in maximal tracheal pressure and phrenic nerve discharge responses caused by hypercapnia. Cooling the intermediate area to 20 degrees C significantly elevated the CO2 thresholds of both responses. These findings demonstrate that structures near the intermediate area of the VMS play a role in the neural cholinergic responses of the tracheal segment to CO2. It is possible that neurons or fibers in intermediate area influence the motor nuclei innervating the trachea. Alternatively, airway tone may be linked to respiratory motor activity so that medullary interventions that influence respiratory motor activity also alter bronchomotor tone.

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Pulmonary response to antigen infusion in the sensitized guinea pig: modification by atropine

Journal of Applied Physiology ◽

10.1152/jappl.1975.39.6.916 ◽

1975 ◽

Vol 39 (6) ◽

pp. 916-919 ◽

Cited By ~ 27

Author(s):

J. M. Drazen ◽

K. F. Austen

Keyword(s):

Pressure Pulse ◽

Weight Ratio ◽

Dry Weight ◽

Dynamic Compliance ◽

Minute Volume ◽

Pulmonary Response ◽

Peripheral Airway ◽

Atropine Treatment ◽

Airway Tone ◽

Central Airway

Alterations in pulmonary conductance, dynamic compliance, respiratory frequency, minute volume, mean arterial pressure, pulse rate, relaxation volume-to-dry weight ratio, and wet-to-dry weight ratio resulting from antigen infusion in sensitized guinea pigs was examined with and without atropine treatment. In untreated animals 3 min after antigen infusion there were significant decreases in dynamic compliance and pulmonary conductance with an increase in relaxation volume-to-dry weight ratio while other parameters were not altered. In atropine-treated animals antigen infusion resulted in a decreased dynamic compliance and an increased relaxation volume-to-dry weight ratio but no significant change in pulmonary conductance. This suggests that the alterations in large and central airway tone resulting from antigen infusion are mediated predominantly by secondary cholinergic mechanisms while peripheral airway effects are mainly noncholinergic.

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Reflex effects of left heart and pulmonary vascular distension on airways of dogs

Journal of Applied Physiology ◽

10.1152/jappl.1980.49.4.620 ◽

1980 ◽

Vol 49 (4) ◽

pp. 620-626 ◽

Cited By ~ 16

Author(s):

T. C. Lloyd

Keyword(s):

Dynamic Compliance ◽

Pulmonary Congestion ◽

Wall Tension ◽

Left Heart ◽

Pulmonary Vessels ◽

Vascular Congestion ◽

Inspiratory Resistance ◽

Anesthetized Dogs ◽

Lung Vessels ◽

Airway Tone

Two types of experiments were performed in anesthetized dogs on cardiopulmonary bypass to see if pulmonary vascular congestion and left heart distension would induce reflex bronchoconstriction. First we distended the isolated left heart and lung vessels with blood while ventilating the lungs and measuring airflow, tidal volume, and transpulmonary pressures. Congestion reduced dynamic compliance and increased inspiratory resistance. Vagotomy increased compliance and decreased resistance but did not alter the effects of congestion. Then we measured changes in tracheal wall tension while we separately distended the pulmonary vessels and left heart. Left heart distension increased tracheal tension, whereas pulmonary congestion increased tension in some dogs but decreased it in others. All effects were eliminated by vagotomy. We concluded that although left heart distension and pulmonary vascular congestion may reflexly increase airway tone, pulmonary congestion may at some times reflexly reduce tone. None of these reflex changes, however, appear to be important in the modest (approximately 20%) changes in airflow dynamics observed during combined left heart and pulmonary vascular distension.

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Effect of volume history on distribution of inspired gas in asthmatics

Journal of Applied Physiology ◽

10.1152/jappl.1987.62.3.1179 ◽

1987 ◽

Vol 62 (3) ◽

pp. 1179-1185 ◽

Cited By ~ 1

Author(s):

R. B. Filuk ◽

N. R. Anthonisen

Keyword(s):

Vital Capacity ◽

Total Lung Capacity ◽

Lung Parenchyma ◽

Phase Iii ◽

Ventilation Distribution ◽

Lung Capacity ◽

Beta Agonists ◽

Airway Tone ◽

Washout Curves ◽

Volume History

Twelve stable adult asthmatics slowly inhaled boluses of He at 20, 40, or 60% vital capacity (VC); these volumes were achieved either by expiring from total lung capacity (TLC) or by inspiring from residual volume (RV). Inspirations were continued to TLC and then were followed by slow expirations to RV while expired He was measured as a function of expired volume. At 20% VC slopes of alveolar plateaus (phase III) were positive, at 40% VC they were flat, and at 60% VC they were negative; at 20 and 60% VC the slopes were steeper than those in normals. When boluses were administered at 40 and 60% VC, He washout curves were independent of lung volume history. However at 20% VC the slope of phase III was significantly less positive when boluses were given after inspiration from RV than after expiration from TLC. In eight subjects, who were given inhaled beta-agonists, slopes of all He washouts decreased and became independent of volume history at 20% VC. We conclude that in asthmatics at low lung volumes the airways that determine ventilation distribution behave as though they have less hysteresis than the lung parenchyma probably due to increased airway tone.

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