Histamine-induced constriction of canine peripheral lung: an airway or tissue response?

1991 ◽  
Vol 71 (1) ◽  
pp. 287-293 ◽  
Author(s):  
M. S. Ludwig ◽  
F. M. Robatto ◽  
P. D. Sly ◽  
M. Browman ◽  
J. H. Bates ◽  
...  
Keyword(s):  
Pressure Drop ◽  
Airway Resistance ◽  
Linear Motor ◽  
Tissue Response ◽  
Alveolar Region ◽  
Peripheral Airways ◽  
Peripheral Lung ◽  
Peripheral Airway ◽  
Baseline Conditions ◽  
Measured Pressure

We compared the histamine responsiveness of peripheral airways (less than 6.0 mm diam) and parenchymal tissues in eight anesthetized paralyzed open-chest mongrel dogs. We measured pressure in a peripheral bronchus by using an antegrade wedged catheter and pressure in the alveolar region subtended by the wedged bronchus by using an alveolar capsule. Sinusoidal volume oscillations at a frequency of 0.5 Hz were delivered by a linear motor pump into the segment through the wedged catheter. We calculated the resistance of the segment (Rseg) and partitioned Rseg into tissue viscance (i.e., proportional to the resistive pressure drop between the alveolus and the pleura) and peripheral airway resistance. Measurements were taken under baseline conditions and after delivery of increasing concentrations of aerosolized histamine (0.1 micrograms/ml to 100.0 mg/ml) into the segment. We found that the histamine responsiveness of the peripheral airways and lung tissues varied markedly within a given dog. In four of eight dogs the airways were more responsive to histamine, in three of eight the tissues were more responsive, and in one of eight the response was equivalent at the two sites. We conclude that in a given animal, there is marked heterogeneity in the histamine responsiveness of the peripheral airways and parenchymal tissues and that either may dominate responsiveness in the peripheral lung.

Partitioning of pulmonary function in rabbits during cholinergic stimulation

1995 ◽  
Vol 78 (4) ◽  
pp. 1242-1249 ◽  
Author(s):  
S. D. Fuller ◽  
A. N. Freed
Keyword(s):  
Left Lung ◽  
Main Stem Bronchus ◽  
Peripheral Airways ◽  
Peripheral Lung ◽  
Lung Resistance ◽  
Peripheral Airway ◽  
Alveolar Tissue ◽  
The Right ◽  
Central Airway ◽  
Phase Relationships

Our goal was to partition whole lung resistance (RL) and cholinergic reactivity in rabbits into central airway, peripheral airway, and alveolar tissue (Rt) resistances by using forced oscillation (2 Hz), a retrograde catheter, and an alveolar capsule. Central and peripheral airway resistances accounted for approximately 80% of the baseline RL. However, immediately after acetylcholine challenge, Rt was negative. Bilateral vagal stimulation made Rt negative when the capsule was located on the left lung and not on the right lung. Stimulating either vagus produced a negative Rt in the lung ipsilateral to the stimulated nerve. Partial occlusion of the right main-stem bronchus with a balloon also made Rt negative. These results suggest that heterogeneous airflow exists at the level of the alveolar capsule during bronchoconstriction. Phase relationships between tracheal flow and retrograde catheter pressure suggest that flow at the level of the catheter was homogeneous. Thus, using only tracheal and retrograde catheter pressures, we repartitioned RL into its central airway and peripheral lung components. We conclude that cholinergic reactivity resides predominantly in the peripheral lung and that its peripheral location may be due largely to the development of heterogeneous airflow in peripheral airways.

Eicosanoids modulate hyperpnea-induced bronchoconstriction in canine peripheral airways

1996 ◽  
Vol 81 (3) ◽  
pp. 1255-1263 ◽  
Author(s):  
C. Omori ◽  
P. Tagari ◽  
A. N. Freed
Keyword(s):  
Bronchoalveolar Lavage ◽  
Wall Temperature ◽  
Airway Resistance ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Airway Wall ◽  
Airway Reactivity ◽  
Dry Air ◽  
Peripheral Airways ◽  
Peripheral Airway

We examined the role of leukotrienes (LTs) in the development of dry air-induced bronchoconstriction (AIB) in canine peripheral airways. Airway reactivity to exogenous LTs was first tested by using an LTD4 aerosol challenge: peripheral airway resistance increased approximately 130 +/- 51% (n = 4) above baseline when compared with its vehicle control. AIB was then assessed by measuring peripheral airway resistance after, and airway wall temperature during, a dry air challenge (DAC). Treatment with a peptidoleukotriene biosynthesis inhibitor (MK-0591) attenuated AIB by approximately 65% without altering airway wall temperature. The fact that MK-0591 did not alter airway reactivity to aerosolized acetylcholine and completely inhibited Ca2+ ionophore-induced LTB4 generation in canine whole blood attests to the specificity of the drug. Treatment with MK-0591 did not affect the increased number of epithelial cells recovered in bronchoalveolar lavage fluid 5 min after DAC. Concentrations of LTs and other eicosanoids in bronchoalveolar lavage fluid from vehicle-treated DAC airways were increased above baseline values; only LTs were reduced by MK-0591. Before MK-0591, AIB was significantly correlated with the dry air-induced generation of LTC4, LTD4, and LTE4. After treatment with MK-0591, AIB was correlated with thromboxane B2, prostaglandin (PG) F2 alpha, and PGE2. We conclude that hyperpnea with dry air stimulates local production and release of LTs in canine bronchi and, alone with the generation of bronchoconstricting and bronchodilating PGs, plays a central role in the modulation of AIB.

The vulnerable small airway

PEDIATRICS ◽  
1977 ◽  
Vol 59 (5) ◽  
pp. 783-785
Author(s):  
V. Chernick
Keyword(s):  
Flow Resistance ◽  
Gas Flow ◽  
Airway Resistance ◽  
Clear Understanding ◽  
Small Airways ◽  
Peripheral Airways ◽  
Pulmonary Flow ◽  
Peripheral Airway ◽  
First Time

Fundamental physiological work in the late 1960s provided for the first time a clear understanding of (1) the role of the small airways (< 2 mm in diameter) in determining overall airway resistance to gas flow and (2) the relationship between central and peripheral airway resistance and lung growth.1,2 Involvement of the small airways early in the course of cystic fibrosis has been previously commented upon and documented in Pediatrics.3-5 After the age of about 5 years, the flow resistance of peripheral airways constitutes only about 10% to 20% of total pulmonary flow resistance,2 a fraction so small that conventional measurement of total resistance cannot detect small changes in the peripheral component.

Lemakalim attenuates hypocapnia- and dry air-induced bronchoconstriction in canine peripheral airways

1993 ◽  
Vol 75 (1) ◽  
pp. 86-92 ◽  
Author(s):  
K. S. Lindeman ◽  
A. N. Freed
Keyword(s):  
Airway Resistance ◽  
Channel Blocker ◽  
K Channel ◽  
Dry Air ◽  
Peripheral Airways ◽  
Airway Constriction ◽  
Before And After ◽  
Peripheral Airway ◽  
Anesthetized Dogs ◽  
K Channel Opener

To determine the effect of changes in potassium (K+) flux on airway constriction, we studied effects of lemakalim, a K+ channel opener, and glibenclamide, an ATP-sensitive K+ channel blocker. A wedged bronchoscope technique was used to measure peripheral airway resistance (Rp) in anesthetized dogs. Rp was measured before and after constriction of the airways by hypocapnic challenge, acetylcholine aerosol, or dry air hyperpnea. Lemakalim (5 micrograms/kg i.v.) was administered, and the challenge was repeated. Lemakalim attenuated responses to hypocapnia by 72 +/- 7% (n = 6, P = 0.0007) and to dry air challenge by 37 +/- 8% (n = 6, P = 0.005) but not to acetylcholine. On separate days, sublobar segments were pretreated with aerosolized glibenclamide (2 mg/ml), and responses to hypocapnic challenge were measured before and after lemakalim (5 micrograms/kg i.v.), nifedipine (20 micrograms/kg i.v.), or albuterol (1 microgram/kg i.v.). In the presence of glibenclamide, lemakalim had no significant effect on responses to hypocapnia; however, both nifedipine (n = 6, P = 0.0003) and albuterol (n = 6, P = 0.0001) attenuated responses to hypocapnic challenge. These findings suggest that lemakalim attenuated hypocapnic bronchoconstriction by promoting K+ efflux through ATP-sensitive K+ channels.

A beta 2-adrenergic agonist inhibits dry air-induced injury in canine peripheral airways

1995 ◽  
Vol 78 (6) ◽  
pp. 2169-2179 ◽  
Author(s):  
C. Omori ◽  
B. H. Schofield ◽  
W. Mitzner ◽  
A. N. Freed
Keyword(s):  
Airway Resistance ◽  
Ciliated Cell ◽  
Mucosal Damage ◽  
Mast Cell Degranulation ◽  
Adrenergic Agonist ◽  
Dry Air ◽  
Peripheral Airways ◽  
Peripheral Airway ◽  
Anesthetized Dogs ◽  
Beta 2

We examined the effects of a beta 2-agonist on dry air-induced injury in canine peripheral airways. Dry air-induced bronchoconstriction (AIB) was assessed by measuring peripheral airway resistance in anesthetized dogs. Salbutamol reduced AIB by approximately 75% compared with control values. Colloidal carbon was used to detect bronchovascular leakage in contralateral sublobar segments that were pretreated with saline or salbutamol. About 87% of the perimeter of bronchi was damaged after dry air challenge in saline-treated segments. Salbutamol reduced mucosal damage by approximately 30% (P < 0.05). The mucosa of bronchioles was not injured. The average goblet-to-ciliated cell ratio (which reflects mucosal perturbation) in bronchi decreased from 0.38 in control bronchi to 0.15 in challenged bronchi, and this effect was also evident in bronchioles. Salbutamol did not affect this decrement. Dry air challenge also caused degranulation of mast cells located below damaged mucosa, dilation of bronchial vessels, and leakage from capillaries and venules located below normal ciliated and damaged mucosa of bronchi. Thus, we conclude that salbutamol attenuates epithelial damage and AIB but fails to inhibit mast cell degranulation and vascular hyperpermeability.

Control of bronchomotor tone during perinatal development in sheep

1993 ◽  
Vol 75 (4) ◽  
pp. 1486-1496 ◽  
Author(s):  
J. J. Perez Fontan ◽  
L. P. Kinloch
Keyword(s):  
Airway Resistance ◽  
Vagal Stimulation ◽  
Peripheral Resistance ◽  
Term Newborn ◽  
Peripheral Airways ◽  
Pleural Surface ◽  
Peripheral Airway ◽  
Cervical Vagotomy ◽  
Central Airway ◽  
Bronchomotor Tone

To characterize the perinatal maturation of the cholinergic control of the airways, we compared the effects of bilateral cervical vagotomy and supramaximal vagal stimulation on the airway resistances of 7 premature (130–133 days of gestation), 11 term newborn, and 9 9-wk-old lambs anesthetized with pentobarbital. Resistances were partitioned between central and peripheral airways with catheters placed retrogradely into peripheral bronchi and capsules attached to the pleural surface in communication with subpleural air spaces. The central and peripheral airway resistances of premature and term newborn lambs and the peripheral resistance of 9-wk-old lambs decreased after vagotomy but only when the lungs were ventilated with small tidal volumes at mean transpulmonary pressures < or = 7.5 cmH2O. Vagotomy caused smaller absolute changes in central airway resistance than vagal stimulation. In contrast, both vagotomy and vagal stimulation produced similar absolute changes in peripheral airway resistance, indicating that resting cholinergic outflow is preferentially distributed to the peripheral airways even at the earlier ages. The effects of vagal stimulation on airway resistance were prevented by atropine. Our results prove that a resting bronchomotor tone can be present in both central and peripheral airways before the term of gestation in sheep. This tone depends on the activity of cholinergic fibers in the vagus and can be regionally controlled.

Hyperpnea with dry air causes time-dependent alterations in mucosal morphology and bronchovascular permeability

1995 ◽  
Vol 78 (3) ◽  
pp. 1043-1051 ◽  
Author(s):  
C. Omori ◽  
B. H. Schofield ◽  
W. Mitzner ◽  
A. N. Freed
Keyword(s):  
Airway Resistance ◽  
Ciliated Cell ◽  
Mucosal Injury ◽  
Cell Number ◽  
Physiological Changes ◽  
Dry Air ◽  
Peripheral Airways ◽  
Peripheral Airway ◽  
Mast Cell Number ◽  
Mucosal Morphology

This study examines the morphological and physiological changes that occur in canine peripheral airways after hyperpnea with dry air. Peripheral airways were exposed to a 5-min 2,000 ml/min dry air challenge (DAC) at 24, 6, 2, or 1 h before or 60 s after (0 h) the injection of colloidal carbon. After recording the dry air-induced increase in peripheral airway resistance, the lungs were removed and prepared for morphometric analysis (n = 5). Light microscopy revealed that 50% of the airway perimeter appeared damaged at 0, 1, and 2 h after DAC, and repair was evident 6–24 h after the challenge. The average goblet-to-ciliated cell ratio decreased from 0.34 before DAC to 0.15 after DAC and recovered within 24 h. Dry air-induced bronchovascular leakage occurred immediately after DAC and persisted for > or = 24 h. DAC decreased mast cell number only in regions where the mucosa was damaged, and this decrease was inversely correlated with bronchovascular leakage. Finally, leukocyte infiltration was evident 1–2 h after DAC and continued throughout the 24-h period. We conclude that hyperpnea with dry air causes mucosal injury, inflammation, and microvascular leakage and that these dry air-induced effects persist for > or = 24 h after DAC.

Dose-response curves of central and peripheral airways to nicotine injections in dogs

1986 ◽  
Vol 61 (5) ◽  
pp. 1677-1685 ◽  
Author(s):  
M. Nakamura ◽  
T. Haga ◽  
M. Miyano ◽  
H. Sasaki ◽  
T. Takishima
Keyword(s):  
Dose Response ◽  
Airway Resistance ◽  
Suppressive Effect ◽  
Response Curves ◽  
Parasympathetic Ganglia ◽  
Peripheral Airways ◽  
Peripheral Airway ◽  
Anesthetized Dogs ◽  
Vagal Reflex ◽  
Dose Response Curves

The dose-response curves of the central and peripheral airways to intravenously injected nicotine were studied in 55 anesthetized dogs. With intact vagi, nicotine caused a dose-dependent increase in central airway resistance (Rc) similar to the increase in peripheral airway resistance (Rp) at concentrations ranging from 4 to 64 micrograms/kg. However, the responses of both Rc and Rp fell progressively when sequential doses of nicotine greater than 256 micrograms/kg were administered. With intact vagi and the administration of propranolol, there was a greater increase in Rp than in Rc at a nicotine dose of 64 micrograms/kg (P less than 0.05). With vagotomy, the responsiveness of both central and peripheral airways to nicotine decreased with doses of nicotine less than 64 micrograms/kg, but with doses of nicotine greater than 256 micrograms/kg the suppressive effect of nicotine on both Rc and Rp was less than that seen with intact vagi. Under conditions in which the vagi were cut and atropine administered, the responsiveness of nicotine was even further depressed. Combinations either of atropine and chlorpheniramine or atropine and phenoxybenzamine also completely blocked reactions to nicotine. Additionally reactions to nicotine were completely blocked by hexamethonium. These results suggest that nicotine increases both Rc and Rp mainly through a vagal reflex and stimulation of the parasympathetic ganglia.

Positive Expiratory Pressure: A Potential Therapy to Mitigate Acute Bronchoconstriction in the Asthma of Obesity

2021 ◽  
Author(s):  
Swati a. Bhatawadekar ◽  
Anne E. Dixon ◽  
Ubong Peters ◽  
Nirav Daphtary ◽  
Kevin Hodgdon ◽  
...  
Keyword(s):  
Airway Resistance ◽  
Late Onset ◽  
Rescue Therapy ◽  
Pharmacologic Therapy ◽  
Airway Closure ◽  
Airway Narrowing ◽  
Asthma Patients ◽  
Peripheral Airway ◽  
Central Airway ◽  
Positive Expiratory Pressure

Late-onset non-allergic (LONA) asthma in obesity is characterized by increased peripheral airway closure secondary to abnormally collapsible airways. We hypothesized that positive expiratory pressure (PEP) would mitigate the tendency to airway closure during bronchoconstriction, potentially serving as rescue therapy for LONA asthma of obesity. The PC20 dose of methacholine was determined in 18 obese participants with LONA asthma. At each of 4 subsequent visits, we used oscillometry to measure input respiratory impedance (Zrs) over 8 minutes; participants received their PC20 concentration of methacholine aerosol during the first 4.5 minutes. PEP combinations of either 0 or 10 cmH2O either during and/or after the methacholine delivery were applied, randomized between visits. Parameters characterizing respiratory system mechanics were extracted from the Zrs spectra. In 18 LONA asthma patients (14 females, BMI: 39.6±3.4 kg/m2), 10 cmH2O PEP during methacholine reduced elevations in the central airway resistance, peripheral airway resistance and elastance, and breathing frequency was also reduced. During the 3.5 min following methacholine delivery, PEP of 10 cmH2O reduced Ax and peripheral elastance compared to no PEP. PEP mitigates the onset of airway narrowing brought on by methacholine challenge, and airway closure once it is established. PEP thus might serve as a non-pharmacologic therapy to manage acute airway narrowing for obese LONA asthma.

Hypocapnia-induced constriction of the canine peripheral airways exhibits tachyphylaxis

1987 ◽  
Vol 63 (2) ◽  
pp. 497-504 ◽  
Author(s):  
J. Kolbe ◽  
S. R. Kleeberger ◽  
H. A. Menkes ◽  
E. W. Spannhake
Keyword(s):  
Prolonged Exposure ◽  
Atropine Sulfate ◽  
Chlorpheniramine Maleate ◽  
Mechanically Ventilated ◽  
Peripheral Airways ◽  
Airway Constriction ◽  
Peripheral Lung ◽  
Histamine H1 Receptors ◽  
Constrictor Response ◽  
Compensatory Effect

Hypocapnia-induced constriction of peripheral airways may be important in regulating the distribution of ventilation in pathological conditions. We studied the response of the peripheral lung to hypocapnia in anesthetized, paralyzed, mechanically ventilated dogs using the wedged bronchoscope technique to measure resistance of the collateral system (Rcs). A 5-min hypocapnic challenge produced a 161 +/- 19% (mean +/- SE) increase in Rcs. The magnitude of this response was not diminished with repeated challenge or by atropine sulfate (1 mg base/kg iv), chlorpheniramine maleate (5 mg base/kg iv), or indomethacin (5 mg/kg iv). The response was reduced by 75% by isoproterenol (5 micrograms/kg iv) (P less than 0.01) and reduced by 80% by nifedipine (20 micrograms/kg iv) (P less than 0.05). During 30-min exposure to hypocapnia the maximum constrictor response occurred at 4–5 min, after which the response attenuated to approximately 50% of the maximum response (mean = 53%, range 34–69%). Further 30-min challenges with hypocapnia resulted in significantly decreased peak responses, the third response being 50% of the first (P less than 0.001). The inability of indomethacin or propranolol to affect the tachyphylaxis or attenuation of the response suggests that neither cyclooxygenase products nor beta-adrenergic activity was involved. Hence, hypocapnia caused a prompt and marked constrictor response in the peripheral lung not associated with cholinergic mechanisms or those involving histamine H1-receptors or prostaglandins. With prolonged exposure to hypocapnia there was gradual attentuation of the constrictor response with continued exposure and tachyphylaxis to repeated exposure both of which would tend to diminish any compensatory effect of hypocapnic airway constriction on the distribution of ventilation.

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