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.

Central role of cyclooxygenase in the response of canine peripheral airways to antigen

1986 ◽  
Vol 61 (4) ◽  
pp. 1309-1315 ◽  
Author(s):  
S. R. Kleeberger ◽  
J. Kolbe ◽  
N. F. Adkinson ◽  
S. P. Peters ◽  
E. W. Spannhake
Keyword(s):  
Lavage Fluid ◽  
Prostaglandin D2 ◽  
Dependent Manner ◽  
Initial Exposure ◽  
Peripheral Airways ◽  
Peripheral Lung ◽  
Airway Response ◽  
Lung Periphery ◽  
Histamine H1 Receptors

We studied the effects of antigen aerosol challenge on the airways of the canine peripheral lung and examined the roles of cyclooxygenase products, histamine, and cholinergic activity in the responses. One-minute deliveries of 1:10,000 or 1:100,000 concentrations of Ascaris suum antigen aerosol through a wedged bronchoscope resulted in mean maximal increases in collateral system resistance (Rcs) of 415 and 177%, respectively, after 4–8 min. Repeated antigen challenge (1:100,000) resulted in significantly decreased responsiveness to antigen after the initial exposure (P less than 0.005). Bronchoalveolar lavage fluid obtained from the isolated, challenged segment had a significant increase in mean (+/- SE) prostaglandin D2 (PGD2) concentration vs. control (222.0 +/- 65.3 vs. 72.7 +/- 19.5 pg/ml; P less than 0.05); histamine concentrations were variable and not significantly different (4.1 +/- 2.6 vs. 1.2 +/- 0.2 ng/ml; P greater than 0.05). In nine experiments, cyclooxygenase inhibition significantly attenuated the antigen-induced increase in Rcs by 53.4% (P less than 0.001), and the concentration of PGD2 in lavage fluid was reduced by 96.0% (P less than 0.01). Blockade of histamine H1-receptors (n = 8) or cholinergic receptors (n = 7) did not significantly affect the airway response (P greater than 0.05). These data indicate that the canine peripheral lung responds in a dose-dependent manner to antigen aerosol challenge and exhibits characteristics of antigen tachyphylaxis. Results also suggest that cyclooxygenase products play a central role in the acute bronchoconstrictive response of the lung periphery.

scholarly journals Target arterial PO2 according to the underlying pathology: a mini-review of the available data in mechanically ventilated patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Julien Demiselle ◽  
Enrico Calzia ◽  
Clair Hartmann ◽  
David Alexander Christian Messerer ◽  
Pierre Asfar ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Large Scale ◽  
Retrospective Studies ◽  
Prolonged Exposure ◽  
Oxygen Toxicity ◽  
Circulatory Shock ◽  
Mechanically Ventilated ◽  
Ischaemia Reperfusion ◽  
Arterial Po2 ◽  
Underlying Pathology

AbstractThere is an ongoing discussion whether hyperoxia, i.e. ventilation with high inspiratory O2 concentrations (FIO2), and the consecutive hyperoxaemia, i.e. supraphysiological arterial O2 tensions (PaO2), have a place during the acute management of circulatory shock. This concept is based on experimental evidence that hyperoxaemia may contribute to the compensation of the imbalance between O2 supply and requirements. However, despite still being common practice, its use is limited due to possible oxygen toxicity resulting from the increased formation of reactive oxygen species (ROS) limits, especially under conditions of ischaemia/reperfusion. Several studies have reported that there is a U-shaped relation between PaO2 and mortality/morbidity in ICU patients. Interestingly, these mostly retrospective studies found that the lowest mortality coincided with PaO2 ~ 150 mmHg during the first 24 h of ICU stay, i.e. supraphysiological PaO2 levels. Most of the recent large-scale retrospective analyses studied general ICU populations, but there are major differences according to the underlying pathology studied as well as whether medical or surgical patients are concerned. Therefore, as far as possible from the data reported, we focus on the need of mechanical ventilation as well as the distinction between the absence or presence of circulatory shock. There seems to be no ideal target PaO2 except for avoiding prolonged exposure (> 24 h) to either hypoxaemia (PaO2 < 55–60 mmHg) or supraphysiological (PaO2 > 100 mmHg). Moreover, the need for mechanical ventilation, absence or presence of circulatory shock and/or the aetiology of tissue dysoxia, i.e. whether it is mainly due to impaired macro- and/or microcirculatory O2 transport and/or disturbed cellular O2 utilization, may determine whether any degree of hyperoxaemia causes deleterious side effects.

Mucosal injury and eicosanoid kinetics during hyperventilation-induced bronchoconstriction

1999 ◽  
Vol 87 (5) ◽  
pp. 1724-1733 ◽  
Author(s):  
Arthur N. Freed ◽  
Yongqiang Wang ◽  
Sharron McCulloch ◽  
Teresa Myers ◽  
Ryoichi Suzuki
Keyword(s):  
Epithelial Cells ◽  
Mucosal Injury ◽  
Mucosal Damage ◽  
Mediator Release ◽  
Moist Air ◽  
Dry Air ◽  
Peripheral Airways ◽  
Airway Constriction ◽  
Peripheral Airway ◽  
Balf Cell

Bronchoalveolar lavage (BAL) of canine peripheral airways was performed at various times after hyperventilation, and BAL fluid (BALF) cell and mediator data were used to evaluate two hypotheses: 1) hyperventilation-induced mucosal injury stimulates mediator production, and 2) mucosal damage is correlated with the magnitude of hyperventilation-induced bronchoconstriction. We found that epithelial cells increased in BALF immediately after a 2- and a 5-min dry air challenge (DAC). Prostaglandins D2 and F2α and thromboxane B2 were unchanged immediately after a 2-min DAC but were significantly increased after a 5-min DAC. Leukotriene C4, D4, and E4 did not increase until 5 min after DAC. Hyperventilation with warm moist air did not alter BALF cells or mediators and caused less airway obstruction that occurred earlier than DAC. BALF epithelial cells were correlated with mediator release, and mediator release and epithelial cells were correlated with hyperventilation-induced bronchoconstriction. These observations are consistent with the hypothesis that hyperventilation-induced mucosal damage initiates peripheral airway constriction via the release of biochemical mediators.

Time course of respiratory mechanics during histamine challenge in the dog

1992 ◽  
Vol 73 (6) ◽  
pp. 2643-2647 ◽  
Author(s):  
A. M. Lauzon ◽  
G. Dechman ◽  
J. H. Bates
Keyword(s):  
Time Course ◽  
Airway Resistance ◽  
Respiratory Mechanics ◽  
Smooth Muscles ◽  
Atropine Sulfate ◽  
Mechanical Parameters ◽  
Peripheral Airways ◽  
Tissue Resistance ◽  
Histamine Challenge ◽  
Tissue Elastance

We studied the dynamics of respiratory mechanical parameters in anesthetized tracheostomized paralyzed dogs challenged with a bolus of histamine injected either venously (venous group) or arterially (arterial group). The venous group was further divided into two groups: the first was bilaterally vagotomized and received hexamethonium bromide (denervated group), and the second also received atropine sulfate (atropine group). In the venous group, tissue resistance (Rti) and tissue elastance (Eti) increased biphasically, whereas airway resistance was monophasic and synchronized with the second rise of the tissue parameters. In the arterial group, Rti, Eti, and airway resistance increased synchronously. The denervated and atropine groups showed dynamics similar to those of the venous group. We postulate that the first phase observed in Rti and Eti in the venous group is due to constriction of the smooth muscles of the peripheral airways and blood vessels distorting the parenchyma. The second and larger phase is then due to histamine reaching the bronchial circulation and constricting the central airways, again distorting the parenchyma. The results from the arterial group support this hypothesis, whereas those from the denervated group ascertain that none of the phases observed in the venous group was due to nervous reflexes.

Ion Exchange Method for the Separation and Spectrophotometric Determination of Some Sympathomimetic Amines, Antihistamines, and Phenothiazines in Pharmaceuticals

1972 ◽  
Vol 55 (3) ◽  
pp. 596-609
Author(s):  
Donald J Smith
Keyword(s):  
Ion Exchange ◽  
Collaborative Study ◽  
Atropine Sulfate ◽  
Codeine Phosphate ◽  
Chlorpheniramine Maleate ◽  
Sulfonated Polystyrene ◽  
Exchange Method ◽  
Polystyrene Resin ◽  
Acidic Compounds

Abstract An ion exchange procedure has been developed for the separation and quantitative analysis of 32 drugs in various combinations: (a) promethazine HCl with codeine phosphate and potassium guaiacolsulfonate; (b) phenylephrine or phenylpropanolamine HCl with (1) dextromethorphan HBr, potassium guaiacolsulfonate, chlorpheniramine maleate, and/or pyrilamine maleate; (2) dextromethorphan HBr, glyceryl guaiacolate, chlorpheniramine maleate, and/or pyrilamine maleate; (3) dextromethorphan HBr and potassium guaiacolsulfonate; (4) dextromethorphan HBr and glyceryl guaiacolate; (5) dextromethorphan HBr and antihistamine; (6) antihistamine and glyceryl guaiacolsulfonate; (7) antihistamine and potassium guaiacolsulfonate; (8) dextromethorphan HBr; (9) glyceryl guaiacolate; (10) potassium guaiacolsulfonate; (c) promethazine HCl with (1) codeine phosphate or (2) phenylephrine HCl; (d) codeine phosphate and potassium guaiacolsulfonate; (e) chlorpromazine HCl, promazine HCl, or promethazine HCl; (f) phenylephrine HCl; (g) codeine phosphate; (h) perphenazine HCl alone or with amitriptyline HCl; (i) ephedrine sulfate with phenobarbital, theophylline, and glyceryl guaiacolate; (j) l-epinephrine bitartrate alone or with antihistamine; (k) procaine HCl, procainamide HCl, procaine isobutyrate, or tetracaine HCl; (l) quinine sulfate with aminophylline; (m) dextromethorphan HBr with (1) terpin hydrate; (2) antihistamine; (3) potassium guaiacolsulfonate; (4) glyceryl guaiacolate; and (n) atropine sulfate or honiatropine methylbromide. The nitrogenous bases are separated from the excipients by retention on a sulfonated polystyrene resin column. These basic compounds are eluted from the column with the appropriate concentration of HCl and are determined by UV; absorption. The organic acids are retained on the quaternary ammonium anion resin. The acidic compounds are eluted from the columns with the appropriate concentration of HCl and determined by I’V absorption. Average recoveries ranged from 98.6 to 101% in the absence of excipients and 95.8 to 102% with excipients present. The method is recommended for collaborative study.

Serial distribution of airway mechanical properties in dogs: effects of histamine

1994 ◽  
Vol 77 (2) ◽  
pp. 554-566 ◽  
Author(s):  
R. H. Habib ◽  
B. Suki ◽  
J. H. Bates ◽  
A. C. Jackson
Keyword(s):  
Mechanical Properties ◽  
Model Fit ◽  
Control Case ◽  
Frequency Range ◽  
Mechanically Ventilated ◽  
Peripheral Airways ◽  
Direct Measurements ◽  
Airway Opening ◽  
Bolus Intravenous Injection ◽  
Airway Walls

We measured respiratory input impedance (Zin; 8–2,048 Hz) in five dogs (anesthetized, tracheostomized, vagotomized, and mechanically ventilated) during 80 s of apnea after a bolus intravenous injection of saline or histamine (5.0 mg). In the control case, three antiresonances in Zin were found in four of the dogs, whereas in the remaining dog only two were found. The magnitude and frequency of these antiresonances were significantly altered after bronchoconstriction. To interpret Zin, a model incorporating detailed airway geometry, asymmetrical branching, and nonrigid airway walls was developed. The model fit both the saline and histamine Zin data well and predicted a serial distribution of bronchoconstriction consistent with known effects of histamine; i.e., the diameters of the most peripheral airways were reduced (26% of their control values), whereas tracheal diameters were not significantly affected. The model provided estimates of tracheal diameters that were well correlated (r = 0.92) with direct measurements. Control estimates of soft tissue viscosity (1.63 +/- 0.42 cmH2O.s) and Young's modulus (406 +/- 125 cmH2O) compared closely with values in the literature. These results indicate that bronchoconstriction induced by histamine results in significant changes in Zin over this frequency range and that by using this data analysis approach definitive physiological parameters relative to airway geometry and wall mechanical properties can be obtained from measurements made at the airway opening.

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.

EP2 receptor mediates bronchodilation by PGE2 in mice

2000 ◽  
Vol 88 (6) ◽  
pp. 2214-2218 ◽  
Author(s):  
J. R. Sheller ◽  
Daphne Mitchell ◽  
Barbara Meyrick ◽  
John Oates ◽  
Richard Breyer
Keyword(s):  
Cell Metabolism ◽  
Receptor Activation ◽  
Receptor Subtypes ◽  
Wild Type ◽  
Mechanically Ventilated ◽  
Airway Constriction ◽  
Ep Receptor ◽  
Ep2 Receptor ◽  
Muscle Responses

PGE2 is an important cyclooxygenase product that modulates airway inflammatory and smooth muscle responses. Signal transduction is mediated by four EP receptor subtypes that cause distinct effects on cell metabolism. To determine the role of EP2 receptor activation, we produced a mouse lacking the EP2 receptor by targeted gene disruption. The effect of aerosolized PGE2 and other agonists was measured using barometric plethysmography and by measurements of lung resistance in mechanically ventilated mice. Inhalation of PGE2 inhibited methacholine responses in wild-type but not in mice lacking the EP2 receptor [EP2(−/−)]. After airway constriction was induced by methacholine aerosol, PGE2reduced the airway constriction enhanced pause in wild-type mice (from 0.88 ± 0.15 to 0.55 ± 0.06) but increased it in EP2(−/−) mice (from 0.73 ± 0.08 to 1.27 ± 0.19). Similar results were obtained in mechanically ventilated mice. These data indicate that the EP2 receptor mediates the bronchodilation effect of PGE2.

Differential responses of tissue viscance and collateral resistance to histamine and leukotriene C4

1988 ◽  
Vol 65 (3) ◽  
pp. 1424-1429 ◽  
Author(s):  
M. S. Ludwig ◽  
S. A. Shore ◽  
J. J. Fredberg ◽  
J. M. Drazen
Keyword(s):  
Similar Pattern ◽  
Base Line ◽  
Constant Flow ◽  
Leukotriene C4 ◽  
Alveolar Pressure ◽  
Mechanically Ventilated ◽  
Peripheral Lung ◽  
Fractional Increase ◽  
Differential Responses ◽  
Histamine Response

Alterations in tissue viscance (Vti) and collateral resistance (Rcoll) are both used as indexes of peripheral lung responses. However, it is not known whether the two responses reflect the effects of activation of the same contractile elements. We measured differential responses in Vti and Rcoll to histamine and leukotriene (LT) C4 to determine whether each evoked a similar pattern of response. Using the wedged bronchoscope constant-flow technique, we measured Rcoll in lobar segments of anesthetized, paralyzed, open-chest, mechanically ventilated mongrel dogs. In addition, we measured (with an alveolar capsule) alveolar pressure (PA) within the segment under study. This allowed us to calculate Vti, the component of the PA change in phase with segment flow. Rcoll and Vti measurements were obtained under base-line conditions and after local delivery of aerosols generated from histamine and LTC4. In five out of five lobes studied with both histamine and LTC4, the fractional Rcoll response to histamine was greater than the fractional Rcoll response to LTC4. In contrast, in four out of five lobes examined, the fractional increase in Vti accompanying the histamine response was less than the fractional increase in Vti accompanying LTC4 administration. These data suggest that anatomically distinct contractile elements influence Vti and Rcoll insofar as LTC4 and histamine evoke quantitatively different changes in these two indexes of peripheral lung responses.

Reversal of 5HT-induced bronchoconstriction by PGI2: distribution of central and peripheral actions

1980 ◽  
Vol 49 (3) ◽  
pp. 521-527 ◽  
Author(s):  
E. W. Spannhake ◽  
J. L. Levin ◽  
B. T. Mellion ◽  
C. A. Gruetter ◽  
A. L. Hyman ◽  
...  
Keyword(s):  
Lung Compliance ◽  
Pulmonary Mechanics ◽  
Similar Distribution ◽  
Mechanically Ventilated ◽  
Peripheral Airways ◽  
Bolus Intravenous Injection ◽  
Peripheral Areas ◽  
Dynamic Lung Compliance ◽  
Dose Dependent

In anesthetized, mechanically ventilated, and vagotomized cats, we studied the distribution of the bronchodilatory effects of prostaglandin I2 (PGI2) in central and peripheral airways. In the intact-chest cat, bolus intravenous injection of PGI2 in a range of doses from 3 to 100 micrograms produced dose-dependent reversal of 5-hydroxytryptamine- (5HT) induced bronchoconstriction. Bronchodilatory effects were manifested by a pronounced decrease in central airways flow resistance, as estimated by measurement of lung resistance and by an increase in dynamic lung compliance (Cdyn). A similar distribution and magnitude of airway effects were produced by intravenous administration of PGE1 in a range of doses from 0.3 to 10 micrograms. PGI2 significantly reversed the frequency dependence of compliance induced by infusion of 5HT. The PGI2 metabolite, 6-keto-PGF1 alpha, was without effect on pulmonary mechanics. Comparison of right- versus left-heart administration of PGI2 did not point to a significant role of the bronchial circulation in the airway effects of PGI2. Comparison of the effects of PGI2 and PGE1 on cat bronchial and parenchymal strips contracted by 5HT showed both prostaglandins to have predominant action on bronchial smooth muscle with PGI2 being 3-10 times less active than PGE1. These data suggest that PGI2 has central airway bronchodilator activity, similar to, but less potent than PGE1. In addition, they suggest that PGI2 has significant dilator activity in certain peripheral areas of the lung, as well.

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