Airway responses to esophageal acidification

2008 ◽  
Vol 294 (1) ◽  
pp. R211-R219 ◽  
Author(s):  
Ivan M. Lang ◽  
Steven T. Haworth ◽  
Bidyut K. Medda ◽  
David L. Roerig ◽  
Hubert V. Forster ◽  
...  
Keyword(s):  
Dynamic Compliance ◽  
Mucus Secretion ◽  
Transport Rate ◽  
Mucociliary Transport ◽  
Airway Constriction ◽  
Airway Function ◽  
Lung Resistance ◽  
Airway Response ◽  
Airway Responses ◽  
Total Lung Resistance

The effects of esophageal acidification on airway function are unclear. Some have found that the esophageal acidification causes a small increase in airway resistance, but this change is too small to cause significant symptoms. The aims of this study were to investigate the effects of esophageal acidification on multiple measures of airway function in chloralose-anesthetized cats. The esophagus was cannulated and perfused with either 0.1 M PBS or 0.1 N HCl at 1 ml/min as the following parameters were quantified in separate experiments: diameter of bronchi ( n = 5), tracheal mucociliary transport rate ( n = 4), tracheobronchial mucus secretion ( n = 7), and lung function ( n = 6). We found that esophageal acidification for 10–30 min decreased bronchial diameters primarily of the smaller low-resistance airways (10–22%, P < 0.05), decreased tracheal mucociliary transport (53%, 8.7 ± 2.4 vs. 4.1 ± 1.3 mm/min, P < 0.05), increased tracheobronchial mucus secretion (147%, 3.4 ± 0.7 vs. 8.4 ± 2.6 mg/10 min, P < 0.05), and caused no change in total lung resistance or dynamic compliance ( P > 0.05). Considering that tracheal mucociliary transport rate is governed in part by mucus secretion, we concluded that the primary airway response to esophageal acidification observed is increased mucus secretion. Airway constriction may act to assist in rapid secretion of mucus and to increase the effectiveness of coughing while not affecting lung resistance or compliance. Given the buffering capabilities of mucus, esophageal acidification activates appropriate physiological responses that may act to neutralize gastroesophageal reflux that reaches the larynx, pharynx, or lower airways.

scholarly journals Mechanisms of airway responses to esophageal acidification in cats

2016 ◽  
Vol 120 (7) ◽  
pp. 774-783 ◽  
Author(s):  
Ivan M. Lang ◽  
Steven T. Haworth ◽  
Bidyut K. Medda ◽  
Hubert Forster ◽  
Reza Shaker
Keyword(s):  
Alcian Blue ◽  
Periodic Acid ◽  
Transport Rate ◽  
Mucociliary Transport ◽  
Mucous Cells ◽  
Mucous Secretion ◽  
Periodic Acid Schiff ◽  
Apocrine Glands ◽  
Airway Constriction ◽  
Airway Responses

Acid in the esophagus causes airway constriction, tracheobronchial mucous secretion, and a decrease in tracheal mucociliary transport rate. This study was designed to investigate the neuropharmacological mechanisms controlling these responses. In chloralose-anesthetized cats ( n = 72), we investigated the effects of vagotomy or atropine (100 μg·kg−1·30 min−1iv) on airway responses to esophageal infusion of 0.1 M PBS or 0.1 N HCl at 1 ml/min. We quantified 1) diameter of the bronchi, 2) tracheobronchial mucociliary transport rate, 3) tracheobronchial mucous secretion, and 4) mucous content of the tracheal epithelium and submucosa. We found that vagotomy or atropine blocked the airway constriction response but only atropine blocked the increase in mucous output and decrease in mucociliary transport rate caused by esophageal acidification. The mucous cells of the mucosa produced more Alcian blue- than periodic acid-Schiff (PAS)-stained mucosubstances, and the mucous cells of the submucosa produced more PAS- than Alcian blue-stained mucosubstances. Selective perfusion of the different segments of esophagus with HCl or PBS resulted in significantly greater production of PAS-stained mucus in the submucosa of the trachea adjacent to the HCl-perfused esophagus than in that adjacent to the PBS-perfused esophagus. In conclusion, airway constriction caused by esophageal acidification is mediated by a vagal cholinergic pathway, and the tracheobronchial transport response is mediated by cholinergic receptors. Acid perfusion of the esophagus selectively increases production of neutral mucosubstances of the apocrine glands by a local mechanism. We hypothesize that the airway responses to esophageal acid exposure are part of the innate, rather than acute emergency, airway defense system.

Antenatal steroids, postnatal surfactant, and pulmonary function in premature rabbits

1989 ◽  
Vol 67 (4) ◽  
pp. 1377-1382 ◽  
Author(s):  
I. M. Gladstone ◽  
M. R. Mercurio ◽  
S. G. Devenny ◽  
H. C. Jacobs
Keyword(s):  
Pulmonary Function ◽  
Distress Syndrome ◽  
Pulmonary Function Tests ◽  
Dynamic Compliance ◽  
Pulmonary Mechanics ◽  
Static Compliance ◽  
Antenatal Corticosteroids ◽  
Antenatal Steroids ◽  
Lung Resistance ◽  
Total Lung Resistance

Antenatal corticosteroids reduce the incidence of the respiratory distress syndrome and improve pulmonary mechanics at least in part by mechanisms other than surfactant stimulation. We measured several aspects of pulmonary function in rabbits to better understand the mechanisms involved. Seven does were given intramuscular betamethasone and six were given vehicle on days 25 and 26 of gestation. Delivery was on day 27 (term = 31). Half of the fetuses from each litter were given rabbit surfactant before the first breath. All fetuses were then ventilated at a consistent tidal volume for 1 h. Pulmonary function tests included static and dynamic compliance, expiratory time constant, stress relaxation, total lung resistance, and total lung conductance. Steroid or surfactant treatment increased dynamic compliance, and the effects of both together were greater than either alone. Static compliance was affected more by surfactant than steroids, whereas lung resistance and conductance were affected more by steroids. The differences in action of the two therapies help account for the increased dynamic compliance seen with combination therapy.

Analysis of responses to endothelins 1, 2, and 3 and sarafotoxin 6b in airways of the cat

1991 ◽  
Vol 71 (1) ◽  
pp. 243-251 ◽  
Author(s):  
M. C. Dyson ◽  
P. J. Kadowitz
Keyword(s):  
Transpulmonary Pressure ◽  
Dynamic Compliance ◽  
Blocking Agent ◽  
Aortic Pressure ◽  
Mechanically Ventilated ◽  
Receptor Blocking ◽  
Intravenous Injections ◽  
Thromboxane Receptor ◽  
Lung Resistance ◽  
Airway Responses

Airway responses to endothelin (ET) 1, ET-2, ET-3, and sarafotoxin 6b (S6b) were investigated in paralyzed, anesthetized, mechanically ventilated cats. Intravenous injections of ET-1 (0.11 nmol/kg) increased transpulmonary pressure (Ptp) and lung resistance (RL) and decreased dynamic compliance (Cdyn) in a dose-related manner. Airway responses to ET-1 were decreased significantly by sodium meclofenamate, a cyclooxygenase inhibitor, and by SKF 96148, a thromboxane receptor blocking agent. In terms of relative bronchoconstrictor activity, the thromboxane mimic, U-46619, was threefold more potent than ET-1 on a molar basis in increasing Ptp. ET-1 and ET-3 had similar bronchoconstrictor activity, and these peptides were less potent than ET-2 and S6b. Bronchoconstrictor responses to ET-2, ET-3, and S6b were also decreased significantly by meclofenamate and by thromboxane receptor blocking agents. The ET-1 precursor ET-1-(1–38) (big ET-1) caused a significant slowly developing increase in Ptp, RL, and aortic pressure (PAO) and a decrease in Cdyn, whereas a monocyclic ET-1 analogue and ET-1-(16–21) hexapeptide fragment had little or no activity in the airways. The present data indicate that ET-1, ET-2, ET-3, and S6b have significant bronchoconstrictor activity in the cat and that responses are dependent in part on the release of arachidonic acid and the formation of thromboxane A2. These data also suggest that big ET-1 is converted into a mature peptide in the cat and that ET-1-(16–21) hexapeptide fragment and a monocyclic ET-1 analogue have little if any bronchoconstrictor activity in the anesthetized cat.

Mechanism of substance P-induced bronchoconstriction in maturing rabbit

1984 ◽  
Vol 57 (4) ◽  
pp. 1238-1246 ◽  
Author(s):  
M. M. Grunstein ◽  
D. T. Tanaka ◽  
J. S. Grunstein
Keyword(s):  
Substance P ◽  
Dynamic Compliance ◽  
Atropine Sulfate ◽  
Parasympathetic Ganglia ◽  
Airway Function ◽  
Age Related ◽  
Airway Response ◽  
Cervical Vagotomy ◽  
Release Of Acetylcholine ◽  
Dose Dependent

The maturational effects of substance P (SP) on airway function were quantitatively assessed in 30 anesthetized tracheotomized rabbits ranging in age from 2 to 29 days. Following paralysis, during mechanical ventilation with 100% O2 in a body plethysmograph, respiratory resistance (Rrs) and dynamic compliance (Cdyn) were continuously monitored. Noncumulative systemic infusions of SP (0.001–5.0 micrograms/g) produced dose-dependent decreases in pulmonary conductance (Grs), i.e., 1/Rrs, and Cdyn. The dose of SP producing a 50% decrease in Cdyn (PD50-Cdyn) significantly increased as a function of age indicating a diminution in airway sensitivity to SP. Bilateral cervical vagotomy and ganglionic blockade with hexamethonium had no effect on the airway response to SP. On the other hand, the response was significantly reduced following atropine sulfate infusion (2 mg/kg), suggesting a peripheral cholinergic contribution located distal to the airway parasympathetic ganglia. The magnitude of this cholinergic contribution increased as a function of age. Unlike atropine, antagonists to histamine and 5-hydroxytryptamine had no effect on the airway response to SP, however, the response was inhibited following infusion of the SP antagonist, D-Pro2,D-Trp7,9-SP. These findings indicate that the airway response to SP is age-related and mediated by binding of the agonist to airway smooth muscle coupled with an accelerated release of acetylcholine at the airway neuromuscular junction.

Inhibition of allergic late airway responses by inhaled heparin-derived oligosaccharides

2000 ◽  
Vol 88 (5) ◽  
pp. 1721-1729 ◽  
Author(s):  
Tahir Ahmed ◽  
Jaime Ungo ◽  
Min Zhou ◽  
Carlos Campo
Keyword(s):  
Molecular Weight ◽  
Antigen Challenge ◽  
Antiallergic Activity ◽  
Acute Responses ◽  
Lung Resistance ◽  
Dependent Inhibition ◽  
Airway Response ◽  
Dose Dependent Inhibition ◽  
Airway Responses ◽  
Dose Dependent

Inhaled heparin has been shown to inhibit allergic bronchoconstriction in sheep that develop only acute responses to antigen (acute responders) but was ineffective in sheep that develop both acute and late airway responses (LAR) (dual responders). Because the antiallergic activity of heparin is molecular-weight dependent, we hypothesized that heparin-derived oligosaccharides (<2,500) with potential anti-inflammatory activity may attenuate the LAR in the dual-responder sheep. Specific lung resistance was measured in 24 dual-responder sheep before and serially for 8 h after challenge with Ascaris suum antigen for demonstration of early airway response (EAR) and LAR, without and after treatment with inhaled medium-, low-, and ultralow-molecular-weight (ULMW) heparins and “non-anticoagulant” fractions (NAF) of heparin. Airway responsiveness was estimated before and 24 h postantigen as the cumulative provocating dose of carbachol that increased specific lung resistance by 400%. Only ULMW heparins caused a dose-dependent inhibition of antigen-induced EAR and LAR and postantigen airway hyperresponsiveness (AHR), whereas low- and medium-molecular-weight heparins were ineffective. The effects of ULMW heparin and ULMW NAF-heparin were comparable and inhibited the LAR and AHR even when administered “after” the antigen challenge. The ULMW NAF-heparin failed to inhibit the bronchoconstrictor response to histamine, carbachol, and leukotriene D4, excluding a direct effect on airway smooth muscle. In six sheep, segmental antigen challenge caused a marked increase in bronchoalveolar lavage histamine, which was not prevented by inhaled ULMW NAF-heparin. The results of this study in the dual-responder sheep demonstrate that 1) the antiallergic activity of inhaled “fractionated” heparins is molecular-weight dependent, 2) only ULMW heparins inhibit the antigen-induced EAR and LAR and postantigen AHR, and 3) the antiallergic activity is mediated by nonanticoagulant fractions and resides in the ULMW chains of <2,500.

Effects of neonatal immunization and repeated allergen exposure on airway responsiveness in the rabbit

1996 ◽  
Vol 80 (6) ◽  
pp. 2108-2119 ◽  
Author(s):  
E. Minshall ◽  
D. Spina ◽  
C. P. Page
Keyword(s):  
Pulmonary Function ◽  
Airway Hyperresponsiveness ◽  
Chronic Exposure ◽  
Dynamic Compliance ◽  
Allergen Exposure ◽  
Airway Responsiveness ◽  
Immunization Protocol ◽  
Lung Resistance ◽  
Spontaneously Breathing ◽  
Total Lung Resistance

Neonatal immunization of rabbits has previously been shown to enhance airway responsiveness to inhaled histamine. We investigated the influence of this immunization protocol on pulmonary parameters after inhalation of histamine in littermate allergen-immunized, sham-immunized, and saline-injected rabbits. In spontaneously breathing rabbits, inhalation of histamine caused a concentration-dependent increase in total lung resistance (RL) and respiratory rate (RR) and a reduction in dynamic compliance (Cdyn). Allergen-immunized rabbits were significantly more responsive to histamine than their control littermates and saline-injected animals when the concentration-effect curves were analyzed in terms of changes in RL (P < 0.05), Cdyn (P < 0.05), and RR (P < 0.05) among these groups. The production of allergen-specific immunoglobulins in this model was not correlated to indexes of airway responsiveness (P > 0.05). The effect of inhaled AMP on pulmonary function in allergen-immunized and native animals was also examined. Inhalation of AMP failed to influence Cdyn but elicited significant non-concentration-dependent increases in total RL in allergen-immunized but not naive animals (P < 0.05). Inhalation of AMP also caused a concentration-dependent increase in RR in both allergen-immunized and naive rabbits that was not significantly different (P > 0.05). The influence of biweekly exposure to inhaled or systemic allergen in allergen-immunized rabbits was also examined. Neither repeated systemic nor aerosolized allergen exposure of neonatally immunized rabbits from 3 to 7 mo of age resulted in a further enhancement of airway responsiveness to inhaled histamine. These results suggest that neonatal immunization with Alternaria allergens enhances airway responsiveness to inhaled histamine and AMP. This airway hyperresponsiveness at 3 mo of age could not be enhanced further after chronic exposure to allergen.

Stimulation of parabrachial nuclei dilates airways in cats

1994 ◽  
Vol 76 (4) ◽  
pp. 1712-1718 ◽  
Author(s):  
A. M. Motekaitis ◽  
I. C. Solomon ◽  
M. P. Kaufman
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Dynamic Compliance ◽  
Baroreceptor Reflex ◽  
Homocysteic Acid ◽  
Airway Caliber ◽  
Lung Resistance ◽  
Parabrachial Nuclei ◽  
Total Lung Resistance ◽  
Stimulation Of

Stimulation of the parabrachial nuclei has been shown to increase mean arterial pressure as well as to terminate inspiration. Nevertheless, the effect on airway caliber evoked by stimulation of the parabrachial nuclei is not known. Therefore, in chloralose-anesthetized cats, we microinjected DL-homocysteic acid (25 nl; 100 mM) into 44 sites in or near the lateral and medial parabrachial nuclei while calculating breath-by-breath total lung resistance and dynamic compliance. We found that, in 43 of these sites, microinjection of this excitatory amino acid consistently decreased total lung resistance but had no effect on dynamic compliance. The decrease in lung resistance was caused by a withdrawal of cholinergic tone to the airways. We could find no evidence that the decrease in total lung resistance evoked by stimulation of the parabrachial nuclei was caused by activation of either beta-adrenergic or nonadrenergic noncholinergic pathways. The decrease in total lung resistance evoked by stimulation of the parabrachial nuclei was not secondary to the baroreceptor reflex even though microinjection frequently increased mean arterial pressure. In addition, microinjection did not have consistent effects on phrenic nerve activity, although in individual circumstances the effect on this activity was quite large. We conclude that stimulation of cell bodies and dendrites in the parabrachial nuclei dilates the airways of anesthetized cats and that the effect is not secondary to the baroreceptor reflex.

Methylprednisolone restores sensitivity to beta-adrenergic agonists in Basenji-Greyhound dogs

1992 ◽  
Vol 72 (2) ◽  
pp. 694-698 ◽  
Author(s):  
R. A. Sauder ◽  
J. D. Tobias ◽  
C. A. Hirshman
Keyword(s):  
Dynamic Compliance ◽  
Pulmonary Resistance ◽  
Beta Adrenergic ◽  
Beneficial Effects ◽  
Airway Constriction ◽  
Beta Adrenergic Agonists ◽  
Methylprednisolone Treatment ◽  
Endogenous Catecholamines ◽  
Airway Responses

This study investigated the effect of chronic methylprednisolone treatment on the ability of albuterol and aminophylline to inhibit methacholine-induced airway constriction in Basenji-Greyhound (BG) dogs in vivo. Pulmonary responsiveness to methacholine was measured in five untreated BG dogs and in the same dogs pretreated with albuterol or aminophylline (which has been shown in this model to release endogenous catecholamines). Each dog was studied before, during, and after daily subcutaneous methylprednisolone for 6 wk. Changes in pulmonary resistance and dynamic compliance with methacholine aerosol challenge were measured. Neither baseline pulmonary function nor pulmonary responsiveness to aerosolized methacholine was significantly altered by albuterol, aminophylline, or chronic methylprednisolone administration alone. However, pretreatment with albuterol or aminophylline significantly attenuated airway responses to methacholine in BG dogs chronically receiving methylprednisolone. Because the reduced sensitivity to albuterol and aminophylline was restored by chronic methylprednisolone treatment, we conclude that at least part of the beneficial effects of corticosteroids on airways in BG dogs is through modulation of beta-adrenergic function.

Blockade of thromboxane responses in the airway of the cat by SQ 29,548

1987 ◽  
Vol 62 (6) ◽  
pp. 2193-2200 ◽  
Author(s):  
D. C. Underwood ◽  
T. Kriseman ◽  
D. B. McNamara ◽  
A. L. Hyman ◽  
P. J. Kadowitz
Keyword(s):  
Receptor Antagonist ◽  
Thromboxane A2 ◽  
Transpulmonary Pressure ◽  
Dynamic Compliance ◽  
Systemic Arterial Pressure ◽  
Pure Substance ◽  
Thromboxane Receptor ◽  
Airway Response ◽  
Airway Responses ◽  
Thromboxane Receptor Antagonist

The effects of SQ 29,548, a thromboxane receptor antagonist, on airway responses were investigated in paralyzed, anesthetized, mechanically ventilated cats. Intravenous injections of the thromboxane and prostaglandin precursor, arachidonic acid (AA), and the thromboxane mimic, U 46619, produced dose-related increases in transpulmonary pressure and lung resistance and decreases in dynamic compliance. After administration of SQ 29,548 (0.5 mg/kg iv), bronchoconstrictor responses to AA were reduced by approximately 50%, whereas responses to U 46619 were reduced by approximately 90%. The cyclooxygenase inhibitor, sodium meclofenamate (2.5 mg/kg iv), blocked the component of the airway response to AA remaining after treatment with SQ 29,548. The thromboxane receptor antagonist had no significant effect on bronchoconstrictor responses to prostaglandins F2 alpha, and D2, methacholine, 5-hydroxytryptamine, histamine, or BAY K 8644, an agent that promotes calcium entry. Reductions in systemic arterial pressure in response to AA were enhanced by the thromboxane receptor antagonist and abolished by meclofenamate. SQ 29,548 had no effect on terminal enzyme activity in microsomal fractions from cat lung. These data support the hypothesis that AA-induced bronchoconstriction in the cat is mediated in large part by the actions of thromboxane A2. These data also suggest that U 46619 and U 44069 stimulate the same airway receptor as thromboxane A2 and mimic the bronchomotor effects of this hormone, which has not yet been isolated as a pure substance. These data demonstrate that SQ 29,548 is a selective thromboxane receptor antagonist in the airways of the closed-chest cat and may be a useful probe for studying responses to thromboxane A2 in physiological and pathophysiological processes in the lung.

Pattern and mechanism of airway response to hypocapnia in normal subjects

1979 ◽  
Vol 47 (1) ◽  
pp. 8-12 ◽  
Author(s):  
C. F. O'Cain ◽  
M. J. Hensley ◽  
E. R. McFadden ◽  
R. H. Ingram
Keyword(s):  
Vital Capacity ◽  
Normal Subjects ◽  
Oxygen Mixture ◽  
Flow Volume ◽  
Mixture Density ◽  
Lung Capacity ◽  
Airway Constriction ◽  
Maximal Expiratory Flow ◽  
Airway Response ◽  
Expiratory Flow

We examined the bronchoconstriction produced by airway hypocapnia in normal subjects. Maximal expiratory flow at 25% vital capacity on partial expiratory flow-volume (PEFV) curves fell during hypocapnia both on air and on an 80% helium- 20% oxygen mixture. Density dependence also fell, suggesting predominantly small airway constriction. The changes seen on PEFV curves were not found on maximal expiratory flow-volume curves, indicating the inhalation to total lung capacity substantially reversed the constriction. Pretreatment with a beta-sympathomimetic agent blocked the response, whereas atropine pretreatment did not, suggesting that hypocapnia affects airway smooth muscle directly, not via cholinergic efferents.

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