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.

Airway resistance and tissue elastance from input or transfer impedance in bronchoconstricted monkeys

2001 ◽  
Vol 90 (2) ◽  
pp. 571-578 ◽  
Author(s):  
Kristin R. Black ◽  
Bela Suki ◽  
Jeffrey B. Madwed ◽  
Andrew C. Jackson
Keyword(s):  
Airway Resistance ◽  
Nonhuman Primates ◽  
Lung Parenchyma ◽  
Airway Wall ◽  
Tissue Properties ◽  
Cynomolgus Monkeys ◽  
Airway Constriction ◽  
Tissue Resistance ◽  
System Input ◽  
Tissue Elastance

Ascaris suum (AS) challenge in nonhuman primates is used as an animal model of human asthma. The primary goal of this study was to determine whether the airways and respiratory tissues in monkeys that are bronchoconstricted by AS inhalation behave similarly to those in asthmatic humans. Airway resistance (Raw) and tissue elastance (Eti) were estimated from respiratory system input (Zin) or transfer (Ztr) impedance. Zin (0.4–20 Hz) and Ztr (2–128 Hz) were measured in anesthetized cynomolgus monkeys ( n = 10) under baseline (BL) and post-AS challenge conditions. Our results indicate that AS challenge in monkeys produces 1) predominately an increase in Raw and not tissue resistance, 2) airway wall shunting at higher AS doses, and 3) heterogeneous airway constriction resulting in a decrease of lung parenchyma effective compliance. We investigated whether the airway and tissue properties estimated from Zin and Ztr were similar and found that Raw estimated from Zin and Ztr were correlated [ r 2 = 0.76], not significantly different at BL (13.6 ± 1.4 and 13.1 ± 0.9 cmH2O · l−1 · s−1, respectively), but significantly different post-AS (20.5 ± 4.5 cmH2O · l−1 · s−1and 18.5 ± 5.2 cmH2O · l−1 · s−1). There was no correlation between Eti estimated from Zin and Ztr. The changes in lung mechanical properties in AS-bronchoconstricted monkeys are similar to those recently reported in human asthma, confirming that this is a reasonable model of human asthma.

Effects of heterogeneities on the partitioning of airway and tissue properties in normal mice

2007 ◽  
Vol 102 (3) ◽  
pp. 859-869 ◽  
Author(s):  
Satoru Ito ◽  
Kenneth R. Lutchen ◽  
Béla Suki
Keyword(s):  
Mechanical Properties ◽  
Tidal Volume ◽  
Chest Wall ◽  
Airway Resistance ◽  
Mechanical Parameters ◽  
Tissue Properties ◽  
Closed Chest ◽  
Impedance Data ◽  
Open Chest ◽  
Tissue Elastance

We measured the mechanical properties of the respiratory system of C57BL/6 mice using the optimal ventilation waveform method in closed- and open-chest conditions at different positive end-expiratory pressures. The tissue damping (G), tissue elastance (H), airway resistance (Raw), and hysteresivity were obtained by fitting the impedance data to three different models: a constant-phase model by Hantos et al. (Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg JJ. J Appl Physiol 72: 168–178, 1992), a heterogeneous Raw model by Suki et al. (Suki B, Yuan H, Zhang Q, Lutchen KR. J Appl Physiol 82: 1349–1359, 1997), and a heterogeneous H model by Ito et al. (Ito S, Ingenito EP, Arold SP, Parameswaran H, Tgavalekos NT, Lutchen KR, Suki B. J Appl Physiol 97: 204–212, 2004). Both in the closed- and open-chest conditions, G and hysteresivity were the lowest and Raw the highest in the heterogeneous Raw model, and G and H were the largest in the heterogeneous H model. Values of G, Raw, and hysteresivity were significantly higher in the closed-chest than in the open-chest condition. However, H was not affected by the conditions. When the tidal volume of the optimal ventilation waveform was decreased from 8 to 4 ml/kg in the closed-chest condition, G and hysteresivity significantly increased, but there were smaller changes in H or Raw. In summary, values of the obtained mechanical properties varied among these models, primarily due to heterogeneity. Moreover, the mechanical parameters were significantly affected by the chest wall and tidal volume in mice. Contribution of the chest wall and heterogeneity to the mechanical properties should be carefully considered in physiological studies in which partitioning of airway and tissue properties are attempted.

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.

Rapid increase in mast cell numbers in canine central and peripheral airways

1988 ◽  
Vol 65 (1) ◽  
pp. 445-451 ◽  
Author(s):  
C. R. Turner ◽  
J. Kolbe ◽  
E. W. Spannhake
Keyword(s):  
Mast Cell ◽  
Airway Epithelium ◽  
Time Course ◽  
Isotonic Saline ◽  
Cell Movement ◽  
Cell Number ◽  
Small Airways ◽  
Cell Numbers ◽  
Peripheral Airways ◽  
Cell Counts

In preliminary studies of antigen-induced airway inflammation, we noted an apparent increase in peribronchiolar mast cell number. Experiments were thus undertaken to investigate the nature of this migration of mast cells into the central and peripheral airway epithelium and to determine its time course. The tracheae and small airways of 10 anesthetized mongrel dogs were exposed via a bronchoscope to Ascaris suum antigen (Ag), fMet-Leu-Phe (fMLP), ovalbumin (OVA), and isotonic saline (SAL). In the central airways, all stimuli provoked a significant increase (P less than 0.05) in mast cell numbers at the base of the airway epithelium within 3 h. In the peripheral airways, only Ag aerosol stimulated a significant mast cell increase compared with unexposed tissue. In a second series of experiments, the trachea of seven dogs were exposed to 0.026, 0.26, and 2.6 micrograms of Ag. The tissue was collected at 1, 3, 6, and 10 h after exposure. In these experiments, there was a significant mast cell increase seen within 1 h but it was not dose dependent. By 6-10 h after exposure, mast cell counts were not significantly different from the unexposed condition, which is consistent with the idea that some of the cells either degranulated or migrated into the airway lumen. We conclude that mast cell migration is an acute response that can be demonstrated within 1 h of stimulation with Ag. The observation that nonimmunological stimuli may, in some cases, also stimulate mast cell movement affords the possibility that this process represents a generalized response to airway irritation.

Late response of the upper airway of the rat to inhaled antigen

1990 ◽  
Vol 69 (4) ◽  
pp. 1360-1365 ◽  
Author(s):  
L. J. Xu ◽  
D. H. Eidelman ◽  
J. H. Bates ◽  
J. G. Martin
Keyword(s):  
Time Course ◽  
Airway Resistance ◽  
Upper Airway ◽  
Brown Norway ◽  
Control Group ◽  
Late Response ◽  
Lung Elastance ◽  
Upper Airway Resistance ◽  
Airway Responses ◽  
Peak Value

We studied the magnitude and time course of changes in upper airway resistance (Ruaw) of actively sensitized Brown-Norway rats after aerosol challenge with ovalbumin (OA). Two weeks after sensitization, eight rats were challenged by inhalation of aerosolized OA through the nose. The airway responses of these rats 5-10 h after OA challenge were compared with those of seven animals challenged with saline. Seven of eight test rats had increased Ruaw, and six displayed discrete late responses (LR). Ruaw during expiration was highly alinear so analysis was confined to Ruaw during inspiration (Ruaw,I). The Ruaw,I averaged over 5 h was 1.262 +/- 0.09 (SE) cmH2O.ml-1.s, 2.6 times the value for saline-challenged animals (0.476 +/- 0.143 cmH2O.ml-1.s), and it reached a peak value of 3.454 +/- 0.45 cmH2O.ml-1.s. The time to the peak of the LR was 446 +/- 37.3 min. The duration of the LR in the upper airway was 146 +/- 34.9 min. At the time corresponding to the peak value of Ruaw,I, the lung elastance in the test rats was double the value preceding the peak. Lung elastance was unchanged in the control group. We conclude that inhalation of antigen through the upper airway of the sensitized rat results in a substantial increase in upper airway resistance and a distinct LR. The predominant site of the change in respiratory system resistance is in the upper airway.

Contribution of SRF, Elk-1, and myocardin to airway smooth muscle remodeling in heaves, an asthma-like disease of horses

2015 ◽  
Vol 309 (1) ◽  
pp. L37-L45 ◽  
Author(s):  
Mylène Chevigny ◽  
Karine Guérin-Montpetit ◽  
Amandine Vargas ◽  
Josiane Lefebvre-Lavoie ◽  
Jean-Pierre Lavoie
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Serum Response Factor ◽  
Smooth Muscles ◽  
Peripheral Airways ◽  
Myocyte Differentiation ◽  
Antigenic Exposure ◽  
Serum Response ◽  
Muscle Remodeling

Myocyte hyperplasia and hypertrophy contribute to the increased mass of airway smooth muscle (ASM) in asthma. Serum-response factor (SRF) is a transcription factor that regulates myocyte differentiation in vitro in vascular and intestinal smooth muscles. When SRF is associated with phosphorylated (p)Elk-1, it promotes ASM proliferation while binding to myocardin (MYOCD) leading to the expression of contractile elements in these tissues. The objective of this study was therefore to characterize the expression of SRF, pElk-1, and MYOCD in ASM cells from central and peripheral airways in heaves, a spontaneously occurring asthma-like disease of horses, and in controls. Six horses with heaves and five aged-matched controls kept in the same environment were studied. Nuclear protein expression of SRF, pElk-1, and MYOCD was evaluated in peripheral airways and endobronchial biopsies obtained during disease remission and after 1 and 30 days of naturally occurring antigenic exposure using immunohistochemistry and immunofluorescence techniques. Nuclear expression of SRF ( P = 0.03, remission vs. 30 days) and MYOCD ( P = 0.05, controls vs. heaves at 30 days) increased in the peripheral airways of horses with heaves during disease exacerbation, while MYOCD ( P = 0.04, remission vs. 30 days) decreased in the central airways of control horses. No changes were observed in the expression of pElk-1 protein in either tissue. In conclusion, SRF and its cofactor MYOCD likely contribute to the hypertrophy of peripheral ASM observed in equine asthmatic airways, while the remodeling of the central airways is more static or involves different transcription factors.

Partitioning airway and lung tissue resistances in humans: effects of bronchoconstriction

1997 ◽  
Vol 82 (5) ◽  
pp. 1531-1541 ◽  
Author(s):  
David W. Kaczka ◽  
Edward P. Ingenito ◽  
Bela Suki ◽  
Kenneth R. Lutchen
Keyword(s):  
Frequency Dependence ◽  
Lung Tissue ◽  
Airway Resistance ◽  
Broad Band ◽  
Airway Wall ◽  
Lung Elastance ◽  
Tissue Resistance ◽  
Lung Resistance ◽  
High Doses ◽  
Total Lung Resistance

Kaczka, David W., Edward P. Ingenito, Bela Suki, and Kenneth R. Lutchen. Partitioning airway and lung tissue resistances in humans: effects of bronchoconstriction. J. Appl. Physiol. 82(5): 1531–1541, 1997.—The contribution of airway resistance (Raw) and tissue resistance (Rti) to total lung resistance (R l ) during breathing in humans is poorly understood. We have recently developed a method for separating Raw and Rti from measurements of Rland lung elastance (El) alone. In nine healthy, awake subjects, we applied a broad-band optimal ventilator waveform (OVW) with energy between 0.156 and 8.1 Hz that simultaneously provides tidal ventilation. In four of the subjects, data were acquired before and during a methacholine (MCh)-bronchoconstricted challenge. The Rland Eldata were first analyzed by using a model with a homogeneous airway compartment leading to a viscoelastic tissue compartment consisting of tissue damping and elastance parameters. Our OVW-based estimates of Raw correlated well with estimates obtained by using standard plethysmography and were responsive to MCh-induced bronchoconstriction. Our data suggest that Rti comprises ∼40% of total Rlat typical breathing frequencies, which corresponds to ∼60% of intrathoracic Rl. During mild MCh-induced bronchoconstriction, Raw accounts for most of the increase in Rl. At high doses of MCh, there was a substantial increase in Rlat all frequencies and in El at higher frequencies. Our analysis showed that both Raw and Rti increase, but most of the increase is due to Raw. The data also suggest that widespread peripheral constriction causes airway wall shunting to produce additional frequency dependence in El.

scholarly journals Tissue heterogeneity in the mouse lung: effects of elastase treatment

2004 ◽  
Vol 97 (1) ◽  
pp. 204-212 ◽  
Author(s):  
Satoru Ito ◽  
Edward P. Ingenito ◽  
Stephen P. Arold ◽  
Harikrishnan Parameswaran ◽  
Nora T. Tgavalekos ◽  
...  
Keyword(s):  
Airway Resistance ◽  
Compartment Model ◽  
Mouse Lung ◽  
Tissue Elasticity ◽  
Single Compartment Model ◽  
In Series ◽  
Four Levels ◽  
Fitting Error ◽  
Tissue Elastance ◽  
Tissue Element

We developed a network model in an attempt to characterize heterogeneity of tissue elasticity of the lung. The model includes a parallel set of pathways, each consisting of an airway resistance, an airway inertance, and a tissue element connected in series. The airway resistance, airway inertance, and the hysteresivity of the tissue elements were the same in each pathway, whereas the tissue elastance (H) followed a hyperbolic distribution between a minimum and maximum. To test the model, we measured the input impedance of the respiratory system of ventilated normal and emphysematous C57BL/6 mice in closed chest condition at four levels of positive end-expiratory pressures. Mild emphysema was developed by nebulized porcine pancreatic elastase (PPE) (30 IU/day × 6 days). Respiratory mechanics were studied 3 wk following the initial treatment. The model significantly improved the fitting error compared with a single-compartment model. The PPE treatment was associated with an increase in mean alveolar diameter and a decrease in minimum, maximum, and mean H. The coefficient of variation of H was significantly larger in emphysema (40%) than that in control (32%). These results indicate that PPE treatment resulted in increased time-constant inequalities associated with a wider distribution of H. The heterogeneity of alveolar size (diameters and area) was also larger in emphysema, suggesting that the model-based tissue elastance heterogeneity may reflect the underlying heterogeneity of the alveolar structure.

Time-course of impairment of respiratory mechanics after cardiac surgery and cardiopulmonary bypass

1999 ◽  
Vol 27 (8) ◽  
pp. 1454-1460 ◽  
Author(s):  
V. Marco Ranieri ◽  
Nicola Vitale ◽  
Salvatore Grasso ◽  
Filomena Puntillo ◽  
Luciana Mascia ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Time Course ◽  
Respiratory Mechanics

Estimation of time-varying respiratory mechanical parameters by recursive least squares

1991 ◽  
Vol 71 (3) ◽  
pp. 1159-1165 ◽  
Author(s):  
A. M. Lauzon ◽  
J. H. Bates
Keyword(s):  
Least Squares ◽  
Time Course ◽  
Weighted Average ◽  
Recursive Least Squares ◽  
Dynamic Hyperinflation ◽  
Time Varying ◽  
Mechanical Parameters ◽  
Tracheal Pressure ◽  
The Difference ◽  
Estimation Of Time

Continuous estimation of time-varying respiratory mechanical parameters is required to fully characterize the time course of bronchoconstriction. To achieve such estimation, we developed an estimator that uses the recursive linear least-squares algorithm to fit the equation Ptr = RV + EV + K to measurements of tracheal pressure (Ptr) and flow (V). The volume (V) is obtained by numerical integration of V. The estimator has a finite memory with length into the past at each point in time that varies inversely with the difference between the current measurement of Ptr and that predicted by the model, to allow the algorithm to track rapidly varying parameters (R, E, and K). V usually exhibits significant drift and must be corrected. Of the several correction methods investigated, subtraction of the recursively weighted average of V before integration to V was found to perform best. The estimator was tested on simulated noisy data where it successfully followed a fivefold increase in R and a twofold increase in E occurring over 10 s. Three dogs and two cats were anesthetized, paralyzed, tracheostomized, and challenged with a bolus of methacholine (approximately 13 mg/kg iv). Increases of 3- to 10-fold were observed in R and 2- to 3-fold in E, beginning within 10–40 s after the bolus injection. In some animals we found that the increase in E occurred more slowly than that in R, which the V signal suggested was due to dynamic hyperinflation of the lungs. These results demonstrate that our recursive estimator is able to track rapid changes in respiratory mechanical parameters during bronchoconstrictor challenge.

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