Bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

1988 ◽  
Vol 65 (2) ◽  
pp. 934-939 ◽  
Author(s):  
D. W. Ray ◽  
C. Hernandez ◽  
N. Munoz ◽  
A. R. Leff ◽  
J. Solway
Keyword(s):  
Tidal Volume ◽  
Guinea Pigs ◽  
Room Temperature ◽  
Time Course ◽  
Minute Ventilation ◽  
Recovery Period ◽  
Dynamic Compliance ◽  
Base Line ◽  
Stimulus Response ◽  
Airway Response

We demonstrated spontaneous self-limited bronchoconstriction after eucapnic dry gas hyperpnea in 22 anesthetized, mechanically ventilated guinea pigs pretreated with propranolol (1 mg/kg iv). Eucapnic hyperpnea "challenges" of room temperature dry or humidified gas (5% CO2-95% O2) were performed by mechanically ventilating animals (150 breaths/min, 3-6 ml tidal volume) for 5 min. During a "recovery" period after hyperpnea, animals were returned to standard ventilation conditions (6 ml/kg, 60 breaths/min, 50% O2 in air, fully saturated at room temperature). After dry gas hyperpnea (5 ml, 150 breaths/min), respiratory system resistance (Rrs) increased in the recovery period by 7.7-fold and dynamic compliance (Cdyn) decreased by 79.7%; changes were maximal at approximately 3 min posthyperpnea and spontaneously returned to base line in 10-40 min. This response was markedly attenuated by humidification of inspired air. Four consecutive identical dry air challenges resulted in similar posthyperpnea responses in four animals. Increasing the minute ventilation during hyperpnea (by varying tidal volume from 3 to 6 ml) caused increased bronchoconstriction in a dose-dependent fashion in six animals. Neither vagotomy nor atropine altered the airway response to dry gas hyperpnea. We conclude that dry gas hyperpnea in anesthetized guinea pigs results in a bronchoconstrictor response that shares five similar features with hyperpnea-induced bronchoconstriction in human asthma: 1) time course of onset and spontaneous resolution, 2) diminution with humidification of inspired gas, 3) reproducibility on consecutive identical challenges, 4) stimulus-response relationship with minute ventilation during hyperpnea, and 5) independence of parasympathetic neurotransmission.

Tachykinins mediate bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

1989 ◽  
Vol 66 (3) ◽  
pp. 1108-1112 ◽  
Author(s):  
D. W. Ray ◽  
C. Hernandez ◽  
A. R. Leff ◽  
J. M. Drazen ◽  
J. Solway
Keyword(s):  
Tidal Volume ◽  
Guinea Pigs ◽  
Minute Ventilation ◽  
Response Curves ◽  
Mechanically Ventilated ◽  
Stimulus Response ◽  
Respiratory System Resistance ◽  
Water Saturated ◽  
And Control ◽  
Isocapnic Hyperpnea

We tested the hypothesis that tachykinins mediate hyperpnea-induced bronchoconstriction (HIB) in 28 guinea pigs. Stimulus-response curves to increasing minute ventilation with dry gas were generated in animals depleted of tachykinins by capsaicin pretreatment and in animals pretreated with phosphoramidon, a neutral metalloendopeptidase inhibitor. Sixteen anesthetized guinea pigs received capsaicin (50 mg/kg sc) after aminophylline (10 mg/kg ip) and terbutaline (0.1 mg/kg sc). An additional 12 animals received saline (1 ml sc) instead of capsaicin. One week later, all animals were anesthetized, given propranolol (1 mg/kg iv), and mechanically ventilated (6 ml/kg, 60 breaths/min, 50% O2 in air fully water saturated). Phosphoramidon (0.5 mg iv) was administered to five of the noncapsaicin-treated guinea pigs. Eucapnic dry gas (95% O2–5% CO2) hyperpnea “challenges” were performed by increasing the tidal volume (2–6 ml) and frequency (150 breaths/min) for 5 min. Capsaicin-pretreated animals showed marked attenuation in HIB, with a rightward shift of the stimulus-response curve compared with controls; the estimated tidal volume required to elicit a twofold increase in respiratory system resistance (ES200) was 5.0 ml for capsaicin-pretreated animals vs. 3.7 ml for controls (P less than 0.03). Phosphoramidon-treated animals were more reactive to dry gas hyperpnea compared with control (ES200 = 2.6 ml; P less than 0.0001). Methacholine dose-response curves (10(-11) to 10(-7) mol iv) obtained at the conclusion of the experiments were similar among capsaicin, phosphoramidon, and control groups. These findings implicate tachykinin release as an important mechanism of HIB in guinea pigs.

Histamine and leukotrienes mediate pulmonary hypersensitivity to antigen in guinea pigs

1984 ◽  
Vol 56 (4) ◽  
pp. 1032-1038 ◽  
Author(s):  
W. J. Lamm ◽  
Y. L. Lai ◽  
J. Hildebrandt
Keyword(s):  
Guinea Pigs ◽  
Minute Ventilation ◽  
Dynamic Compliance ◽  
Systemic Arterial Pressure ◽  
Antigen Challenge ◽  
Base Line ◽  
Treatment Groups ◽  
Airway Responses ◽  
Experimental Values ◽  
Line P

To study roles of histamine and slow-reacting substance of anaphylasis (SRS-A) in mediating airway responses following antigen challenge, mediator antagonists were administered to guinea pigs sensitized with ovalbumin 10 days before the study. Twenty-three animals were divided into the following five treatment groups: 1) saline only (control 1, n = 5); 2) antigen challenged (n = 5); 3) antigen + methapyrilene (antihistamine, n = 5); 4) FPL 55712 only (SRS-A antagonist, control 2; n = 4), and 5) antigen + FPL 55712 (n = 4). Control groups were not sensitized. Experimental values were compared with those of control 1 at equal times after injections. Pulmonary resistance (RL), dynamic compliance (Cdyn), breathing frequency (f), tidal volume, minute ventilation (VE) and systemic arterial pressure were measured for 15–20 min just before (base line) and for up to 30 min after saline or antigen administration. Antigen challenge alone induced maximal respiratory changes at 5 min. RL increased 131 +/- 28% above base line (P less than 0.05), whereas Cdyn decreased slightly (28 +/- 10%, P less than 0.05). Antihistamine almost eliminated all changes in RL but did not affect decreased Cdyn. On the other hand, FPL 55712 eliminated changes in both RL and Cdyn. Both antagonists blocked the transient increase in VE, but neither blocked the rise in f at 5 min. We conclude that antigen-induced bronchoconstriction (RL) may be primarily mediated by histamine, whereas simultaneous alterations in Cdyn may depend mainly on leukotrienes and those in f depend on neither.

Noninvasive detection of airway constriction in awake guinea pigs

1984 ◽  
Vol 56 (6) ◽  
pp. 1666-1669 ◽  
Author(s):  
S. A. Silbaugh ◽  
J. L. Mauderly
Keyword(s):  
Tidal Volume ◽  
Guinea Pigs ◽  
Reference Signal ◽  
Dynamic Compliance ◽  
Base Line ◽  
Airway Narrowing ◽  
Simple Index ◽  
Airway Constriction ◽  
Compressibility Effects ◽  
Gas Compressibility

Tidal volume measured by the barometric method is very sensitive to increases in compression and expansion of alveolar gas, such as would be expected to occur during airway narrowing or closure. By comparing a barometric method tidal volume signal (VT′) with a reference tidal volume (VT) obtained with a head-out pressure plethysmograph, a simple index related to gas compressibility effects was calculated (VT/VT′). Changes in this index were compared with decreases in dynamic compliance (Cdyn) during histamine aerosol challenge of 15 Charles River Hartley guinea pigs. Decreases in VT/VT′ occurred during all aerosol challenges and were correlated with decreases in Cdyn (r = 0.84, P less than 0.001). Decreases in VT/VT′ were most marked at Cdyn values of less than 50% of base line. At Cdyn of less than 15% of base line, VT′ was 3.1–4.8 times the VT reference signal. No increase in total pulmonary resistance was noted, and Cdyn and VT/VT′ returned to base line after histamine exposure was stopped. We conclude that gas compressibility effects become substantial during histamine-induced airway constriction in the guinea pig and that the VT/VT′ ratio appears to provide a simple noninvasive method of detecting these changes.

Effect of granulocyte depletion on altered lung mechanics after endotoxemia in sheep

1983 ◽  
Vol 55 (1) ◽  
pp. 92-99 ◽  
Author(s):  
J. M. Hinson ◽  
A. A. Hutchison ◽  
M. L. Ogletree ◽  
K. L. Brigham ◽  
J. R. Snapper
Keyword(s):  
Dynamic Compliance ◽  
Lung Mechanics ◽  
Arterial Oxygen ◽  
Base Line ◽  
Mean Pulmonary Arterial Pressure ◽  
Before And After ◽  
Airway Response ◽  
Pulmonary Arterial ◽  
Line P

To examine the role of circulating granulocytes in the airway changes caused by endotoxemia, we measured the response of chronically instrumented unanesthetized sheep to endotoxemia before and after granulocyte depletion with hydroxyurea. Granulocyte depletion did not affect the increases in mean pulmonary arterial pressure caused by endotoxin [peak pressure 59 +/- 8 cmH2O +/- (SE) control, 51 +/- 8 cmH2O granulocyte depleted]. However, the early (30-60 min after endotoxin) airway response to endotoxemia was markedly attenuated. Without granulocyte depletion, endotoxin caused dynamic compliance (Cdyn) to decrease to 41 +/- 10% of the base-line value and total lung resistance (RL) to increase to 283 +/- 61% of base line. When animals were granulocyte depleted, endotoxin decreased Cdyn to 69 +/- 6% (P less than 0.05) of base line and increased RL to 141 +/- 20% of base line (P less than 0.05). Granulocyte depletion also attenuated the effect of endotoxin on arterial oxygenation. During the maximum airway response to endotoxin, the alveolar-to-arterial oxygen gradient was 47 +/- 5 Torr in control studies and 32 +/- 2 Torr in granulocyte depleted studies (P less than 0.05). We conclude that interaction of granulocytes with the lung contributes to the changes in lung mechanics observed following endotoxemia and that the early pulmonary hypertension and the early alterations in lung mechanics caused by endotoxemia are caused by separate processes.

Time course of bronchoconstriction induced by dry gas hyperpnea in guinea pigs

1991 ◽  
Vol 70 (2) ◽  
pp. 504-510 ◽  
Author(s):  
D. W. Ray ◽  
A. Garland ◽  
C. Hernandez ◽  
S. Eappen ◽  
L. Alger ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Room Temperature ◽  
Time Course ◽  
Random Order ◽  
Quiet Breathing ◽  
Mechanically Ventilated ◽  
Abrupt Changes ◽  
Respiratory System Resistance ◽  
Humidified Air ◽  
Isocapnic Hyperpnea

We examined the effects of hyperpnea duration and abrupt changes in inspired gas heat and water content on the magnitude and time course of hyperpnea-induced bronchoconstriction (HIB) in anesthetized mechanically ventilated male Hartley guinea pigs. In 12 animals subjected to 5, 10, and 15 min (random order) of dry gas isocapnic hyperpnea [tidal volume (VT) 4-6 ml, 150 breaths/min) followed by quiet breathing of humidified air (VT 2-3 ml, 60 breaths/min), severe bronchoconstriction developed only after the cessation of hyperpnea; the magnitude of respiratory system resistance (Rrs) increased with the duration of dry gas hyperpnea [peak Rrs 1.0 +/- 0.2, 1.8 +/- 0.3, and 2.3 +/- 0.3 (SE) cmH2O.ml-1.s, respectively]. Seven other guinea pigs received, in random order, 10 min of warm humidified gas hyperpnea, 10 min of room temperature dry gas hyperpnea, and 5 min of dry gas hyperpnea immediately followed by 5 min of warm humidified gas hyperpnea. After each hyperpnea period, the animal was returned to quiet breathing of humidified gas. Rrs rose appreciably after the 10 min of dry and 5 min of dry-5 min of humidified hyperpnea challenges (peak Rrs 1.3 +/- 0.2 and 0.7 +/- 0.2 cmH2O.ml-1.s, respectively) but not after 10 min of humidified hyperpnea (0.2 +/- 0.04 cmH2O.ml-1.s). An additional five animals received 10 min of room temperature dry gas hyperpnea followed by quiet breathing of warm humidified air and 10 min of room temperature dry gas hyperpnea followed by 30 min of warm humidified gas hyperpnea in random order.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of voluntary constraining of thoracic displacement during hypercapnia

1987 ◽  
Vol 63 (5) ◽  
pp. 1822-1828 ◽  
Author(s):  
T. Chonan ◽  
M. B. Mulholland ◽  
N. S. Cherniack ◽  
M. D. Altose
Keyword(s):  
Tidal Volume ◽  
Minute Ventilation ◽  
Free Breathing ◽  
Normal Subjects ◽  
Absolute Difference ◽  
Base Line ◽  
Breathing Frequency ◽  
Inhibitory Feedback ◽  
Function Relationship ◽  
Line Level

The study evaluated the interrelationships between the extent of thoracic movements and respiratory chemical drive in shaping the intensity of the sensation of dyspnea. Normal subjects rated their sensations of dyspnea as PCO2 increased during free rebreathing and during rebreathing while ventilation was voluntarily maintained at a constant base-line level. Another trial evaluated the effects on the intensity of dyspnea, of voluntary reduction in the level of ventilation while PCO2 was held constant. During rebreathing, there was a power function relationship between changes in PCO2 and the intensity of dyspnea. At a given PCO2, constraining tidal volume and breathing frequency to the prerebreathing base-line level resulted in an increase in dyspnea. The fractional differences in the intensity of dyspnea between free and constrained rebreathing were independent of PCO2. However, the absolute difference in the intensity of dyspnea between free and constrained rebreathing enlarged with increasing hypercapnia. At PCO2 of 50 Torr, this difference correlated significantly with the increase in both minute ventilation (r = 0.675) and tidal volume (r = 0.757) above the base line during free rebreathing. Similarly, during steady-state hypercapnia at 50 Torr PCO2, the intensity of dyspnea increased progressively as ventilation was voluntarily reduced from the spontaneously adopted free-breathing level. These results indicate that dyspnea increases with the level of respiratory chemical drive but that the intensity of the sensation is further accentuated when ventilation is constrained below that demanded by the level of chemical drive. This may be explained by a loss of inhibitory feedback from lung or chest wall mechanoreceptors acting on brain stem and/or cortical centers.

Histamine dose-response curves in guinea pigs

1985 ◽  
Vol 58 (2) ◽  
pp. 625-634 ◽  
Author(s):  
W. C. Hulbert ◽  
T. McLean ◽  
B. Wiggs ◽  
P. D. Pare ◽  
J. C. Hogg
Keyword(s):  
Dose Response ◽  
Guinea Pigs ◽  
Response Curve ◽  
Dynamic Compliance ◽  
Dose Response Curve ◽  
Base Line ◽  
Response Curves ◽  
Mechanically Ventilated ◽  
Dose Response Curves ◽  
The Right

Histamine dose-response curves were performed on anesthetized tracheostomized guinea pigs that were paralyzed and mechanically ventilated at a constant tidal volume and breathing frequency. The dose was calculated by generating an aerosol of known concentration and measuring the volume delivered to the lung. Increasing the dose was accomplished by increasing the number of breaths of aerosol delivered. The response to each dose was determined by measuring the change in airway resistance (RL) and dynamic compliance (Cdyn) using the method of Von Neergaard and Wirz (Z. Klin. Med. 105: 51–82, 1927). With increasing doses of histamine, RL increased and reached a plateau at approximately five times the base-line value and Cdyn fell to approximately 20% of its initial value. The variability in the base-line and maximum response as well as the calculated sensitivity and reactivity was less than that previously reported. Propranolol pretreatment increased resting RL and shifted the dose-response curve for RL to the left of the controls, increasing reactivity but not sensitivity. Atropine shifted the dose-response curve to the right of the control, decreasing sensitivity but without changing reactivity. The data for Cdyn showed that atropine pretreatment caused a higher resting value and propranolol pretreatment a lower value at the highest histamine dose but no differences in either sensitivity or reactivity.

Effects of changes in peripheral and central on ventilation during recovery from submergence in ducks

1983 ◽  
Vol 61 (11) ◽  
pp. 2388-2393 ◽  
Author(s):  
William K. Milsom ◽  
David R. Jones ◽  
Geoffrey R. J. Gabbott
Keyword(s):  
Tidal Volume ◽  
Minute Ventilation ◽  
Recovery Period ◽  
Blood Gas ◽  
Breathing Frequency ◽  
Pekin Ducks ◽  
Central Chemoreceptors

The effects of increases in arterial CO2 tension at peripheral and central chemoreceptors on ventilation during recovery from submergence were studied using cross-perfusion techniques on unanaesthetized, White Pekin ducks. Immediately upon surfacing, under normal conditions, minute ventilation [Formula: see text] was elevated four to five times due to roughly equal increases in tidal volume (VT) and breathing frequency (f). Tidal volume returned to resting levels far more rapidly than breathing frequency. If only a peripheral hypercapnia was allowed to develop during diving, it produced the same maximum ventilatory reponse upon surfacing but recovery was much quicker. Central hypercapnia interacted with the peripheral hypercapnia in an additive fashion. There is evidence to suggest that hypercapnia has a greater effect in increasing VT, and hypoxia in increasing f, during the postdive recovery period. The prolonged tachypnea which normally persists after blood gas levels have returned to normal only occurs when hypoxia is allowed to develop during the dive.

Edema affects intra-alveolar fluid pressures and interdependence in dog lungs

1981 ◽  
Vol 51 (4) ◽  
pp. 911-921 ◽  
Author(s):  
J. C. Parker ◽  
R. C. Allison ◽  
A. E. Taylor
Keyword(s):  
Time Course ◽  
Recovery Period ◽  
Positive Pressure ◽  
Base Line ◽  
Alveolar Wall ◽  
Lung Water ◽  
Lung Inflation ◽  
Volume Segment ◽  
The Mean ◽  
Line Pressure

The pressures in occluded, fluid-filled segments of lung were measured in closed-chest supine dogs ventilated with positive pressure at a constant tidal volume. Segment fluid pressures decreased in response to lung inflation and were used with esophageal and airway pressures to calculate an index of bronchiolar-parenchymal interdependence. Animals were subjected to three sequential 5% body wt infusions of Tyrode's solution followed by a 20- to 30 min-recovery period after each infusion. The interdependence index decreased significantly following each infusion, with infusions as small as 1% body wt producing a detectable decrease. The mean pressures in the Tyrode's solution-filled segments generally increased in response to the infusions, but the time course of the response was variable. The base-line pressure in Tyrode's solution-filled segments was -4.8 +/- 2.4 cmH2O. This increased to -1.1 +/- 2.7 cmH2O after a total of 15% body wt had been infused. At the same time, extravascular lung water increased by approximately 17%. Thus negative collapse pressures in the occluded segments were opposed by mechanical stresses transmitted through alveolar wall attachments. This counterbalancing stress was consistently reduced by both increased tissue hydration and increased pulmonary vascular pressure.

Augmentation of parasympathetic contraction in tracheal and bronchial airways by PGF2 alpha in situ

1985 ◽  
Vol 58 (5) ◽  
pp. 1558-1564 ◽  
Author(s):  
A. R. Leff ◽  
N. M. Munoz ◽  
J. Tallet ◽  
M. Cavigelli ◽  
A. C. David
Keyword(s):  
Frequency Response ◽  
Response Curve ◽  
Dynamic Compliance ◽  
Smooth Muscle Contraction ◽  
Base Line ◽  
Frequency Response Curve ◽  
Vagus Nerves ◽  
Response Curves ◽  
Airway Response

We studied the effect of exogenous prostaglandin F2 alpha (PGF2 alpha) on airway smooth muscle contraction caused by parasympathetic stimulation in 22 mongrel dogs in situ. Voltage (0–30 V, constant 20 Hz) and frequency-response (0–25 Hz, 25 V) curves were generated by stimulating the cut ends of both cervical vagus nerves. Airway response was measured isometrically as active tension (AT) in a segment of cervical trachea and as change in airway resistance (RL) and dynamic compliance (Cdyn) in bronchial airways. One hour after 5 mg/kg iv indomethacin, a cumulative frequency-response curve was generated in nine animals by electrical stimulation of the vagus nerves at 15-s intervals. Reproducibility was demonstrated by generating a second curve 7 min later. A third frequency-response curve was generated during active contraction of the airway caused by continuous intravenous infusion of 10 micrograms X kg-1 X min-1PPGF2 alpha. Additional frequency-response studies were generated 15 and 30 min after PGF2 alpha, when airway contractile response (delta RL = +2.8 +/- 0.65 cmH2O X 1(-1) X s; delta Cdyn = -0.0259 +/- 0.007 1/cmH2O) returned to base line. Substantial augmentation of AT, RL, and Cdyn responses was demonstrated in every animal studied (P less than 0.01 for all points greater than 8 Hz) 15 min after PGF2 alpha. At 30 min, response did not differ from initial base-line control. In four animals receiving sham infusion, all frequency-response curves were identical. We demonstrate that PGF2 alpha augments the response to vagus nerve stimulation in tracheal and bronchial airways. Augmentation does not depend on PGF2 alpha-induced active tone.

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