Ontogeny of dry gas hyperpnea-induced bronchoconstriction in guinea pigs

1994 ◽  
Vol 76 (3) ◽  
pp. 1150-1155 ◽  
Author(s):  
T. M. Murphy ◽  
D. W. Ray ◽  
L. E. Alger ◽  
I. J. Phillips ◽  
J. C. Roach ◽  
...  

Adolescent guinea pigs (AGPs) demonstrate dry gas hyperpnea-induced bronchoconstriction (HIB) that shares key features with HIB in humans with asthma. The airways of immature animals exhibit enhanced reactivity to diverse types of stimulation. We tested whether dry gas HIB is also increased in newborn guinea pigs (NGPs). We quantified HIB as the fractional increase of respiratory system resistance (Rrs) over baseline (BL) in five 4- to 7-day-old NGPs after 10 min of hyperpnea, as well as changes in Rrs elicited by intravenous methacholine or capsaicin, and compared these responses with those of AGPs. During hyperpnea, analogous stimuli were delivered by mechanically imposing hyperpnea at 3.0, 4.5, and 6.0 times quiet eucapnic minute ventilation (VE). In AGPs, hyperpnea caused significant bronchoconstriction that increased with VE; peak fractional increase of Rrs was 7.6 +/- 2.0 times BL. In contrast, hyperpnea caused insignificant bronchoconstriction in NGPs (1.4 +/- 0.2 times BL after the largest VE; P < 0.05 vs. AGP). Responses elicited by methacholine (10(-10)-10(-7) mol/kg) or capsaicin (0.01–10.0 microgram/kg) were similar in NGPs and AGPs. In AGPs, hyperpnea suppressed HIB until posthyperpnea. To determine whether the reduced HIB of NGPs was caused by enhanced suppression, NGPs and AGPs were administered acetylcholine (10(-10)-10(-7) mol/kg i.v.) during BL eucapnic ventilation and during eucapnic hyperpnea with warm humidified gas. Responses to acetylcholine were suppressed in AGPs and NGPs to a similar degree. We conclude that HIB is markedly diminished shortly after birth in guinea pigs and that it increases substantially during maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

2002 ◽  
Vol 205 (4) ◽  
pp. 533-538 ◽  
Author(s):  
P. M. MacFarlane ◽  
P. B. Frappell ◽  
J. P. Mortola

SUMMARY We investigated whether the mechanical properties of the respiratory system represent a major constraint to spontaneous breathing in the newborn tammar wallaby Macropus eugenii, which is born after a very short gestation (approximately 28 days, birth mass approximately 380 mg). The rate of oxygen consumption (V̇O2) through the skin was approximately 33 % of the total V̇O2 at day 1 and approximately 14 % at day 6. The mass-specific resting minute ventilation (V̇e) and the ventilatory equivalent (V̇e/V̇O2) were approximately the same at the two ages, with a breathing pattern significantly deeper and slower at day 1. The mass-specific compliance of the respiratory system (Crs) did not differ significantly between the two age groups and was close to the values predicted from measurements in eutherian newborns. Mass-specific respiratory system resistance (Rrs) at day 1 was higher than at day 6, and also higher than in eutherian newborns. Chest distortion, quantified as the degree of abdominal motion during spontaneous breathing compared with that required to inflate the lungs passively, at day 1 was very large, whereas it was modest at day 6. We conclude that, in the tammar wallaby at birth, the high resistance of the respiratory system and the distortion of the chest wall greatly reduce the mechanical efficiency of breathing. At this age, gas exchange through the skin is therefore an important complement to pulmonary ventilation.


1994 ◽  
Vol 76 (4) ◽  
pp. 1432-1438 ◽  
Author(s):  
M. J. Finney ◽  
K. I. Forsberg

We have developed a technique for measuring lung function in conscious guinea pigs using a whole body plethysmograph. Because guinea pigs breathe through the nose, a technique was also developed to measure nasal and lower respiratory system conductance simultaneously in anesthetized animals. The upper and the lower airways could be challenged separately and studied in a manner similar to the conditions in the plethysmograph. Aerosols of histamine, carbachol, or ovalbumin delivered to the nose in sensitized animals had no effect on nasal conductance, even in doses 100 times higher than that required to reduce lower respiratory system conductance. However, intravenous histamine increased nasal conductance. Thus, although nasal resistance constitutes the majority of the total respiratory system resistance measured in the plethysmograph, nasal resistance is unaffected by the aerosol drugs studied. We therefore consider changes in resistance measured in the plethysmograph to originate at or below the larynx. The plethysmographic technique described here is a reliable, reproducible, and rapid technique that enables repeated measurement in animals and minimizes animal trauma.


1989 ◽  
Vol 66 (3) ◽  
pp. 1108-1112 ◽  
Author(s):  
D. W. Ray ◽  
C. Hernandez ◽  
A. R. Leff ◽  
J. M. Drazen ◽  
J. Solway

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.


1982 ◽  
Vol 53 (3) ◽  
pp. 719-725 ◽  
Author(s):  
F. J. Derksen ◽  
N. E. Robinson ◽  
R. F. Slocombe

In awake sensitized ponies, we studied the effect of aerosol ovalbumin challenge on ventilation, pulmonary mechanics, lung volume, and gas exchange before and after vagal blockade. We also challenged the left lung and measured respiratory rate (f) and right and left respiratory system resistance (RrsR, RrsL) before and after both left and bilateral vagal section. Bilateral ovalbumin aerosol challenge increased f, minute ventilation (VE), total respiratory system resistance (Rrs), and minimal volume, decreased dynamic compliance, total lung capacity, and arterial oxygen tension, and was without effect on tidal volume (VT), functional residual capacity, quasi-static lung compliance, and arterial carbon dioxide tension. Vagal blockade reversed the increase in f, VE, and Rrs and increased VT. Challenge of the left lung increased f and RrsL but did not alter RrsR. Bilateral vagal section reversed the tachypnea but unilateral section did not. Histopathologic lesions included acute fibrinopurulent obstructive bronchiolitis, bronchitis, edema, and alveolar distension. We conclude that local mechanisms are of critical importance in the pathogenesis of ovalbumin-induced airway obstruction in ponies, that increased sensitivity of airway smooth muscle to normal vagal tone may also play a role, and that tachypnea following challenge is caused by activity of pulmonary receptors with vagal afferent fibers.


2000 ◽  
Vol 89 (5) ◽  
pp. 1971-1978 ◽  
Author(s):  
O. E. Suman ◽  
J. D. Morrow ◽  
K. A. O'Malley ◽  
K. C. Beck

Airway function deteriorates significantly on cessation of exercise or isocapnic hyperventilation challenges but is largely preserved during the challenge in humans and guinea pigs. PGE2, an endogenous bronchodilator, might be responsible for the preservation of lung function during hyperventilation (HV). We hypothesized that PGE2 might have a protective effect during HV, partially explaining the minimal changes in respiratory system resistance (Rrs) usually seen during HV in humans and guinea pigs. Therefore, changes in Rrs were measured during and after HV in anesthetized, mechanically ventilated guinea pigs treated with flurbiprofen (FBN) or placebo. With HV, there was an initial bronchodilation that was unaffected by FBN. Rrs then increased with time during HV, an effect that was blocked by FBN. After HV, Rrs increased further in all groups, but the increase in Rrs was less in the FBN-treated groups. FBN treatment reduced the PGE2 concentration slightly in lung lavage fluid compared with placebo. We found no enhancement or refractoriness of the Rrs response to repeat bouts of HV and no effect of FBN treatment on the response of Rrs to repeat HV. These results suggest that a constrictor PG is released during and possibly after HV and that the post-HV increase in Rrs is the sum of effects of the PG released during HV and a second constrictor mechanism operating after HV. We found no evidence for bronchodilator PG during or after HV in the guinea pig.


1973 ◽  
Vol 95 (3) ◽  
pp. 335-339
Author(s):  
H. T. Milhorn ◽  
W. J. Reynolds

Experimental human data, obtained for the development and evaluation of a digital computer model of the human respiratory system, are presented. The data are from two series of experiments. In the first series the transient responses of tidal volume, respiratory frequency, minute ventilation, alveolar Pco2 and alveolar Po2 were obtained for several inspired CO2 concentrations (3, 5, 6, and 7 percent). In the second series, transient responses of the same variables were obtained for steps of inspired O2 concentration from room air to several lower oxygen levels (9, 8, and 7 percent). An example of the use of the data for the development and evaluation of a model is indicated.


2016 ◽  
Vol 42 (5) ◽  
pp. 333-340
Author(s):  
Thiago Brasileiro de Vasconcelos ◽  
Fernanda Yvelize Ramos de Araújo ◽  
João Paulo Melo de Pinho ◽  
Pedro Marcos Gomes Soares ◽  
Vasco Pinheiro Diógenes Bastos

ABSTRACT Objective: To evaluate the effects of passive inhalation of cigarette smoke on the respiratory system of guinea pigs. Methods: Male guinea pigs were divided into two groups: control and passive smoking, the latter being exposed to the smoke of ten cigarettes for 20 min in the morning, afternoon and evening (30 cigarettes/day) for five days. After that period, inflammatory parameters were studied by quantifying mesenteric mast cell degranulation, as well as oxidative stress, in BAL fluid. In addition, we determined MIP, MEP, and mucociliary transport (in vivo), as well as tracheal contractility response (in vitro). Results: In comparison with the control group, the passive smoking group showed a significant increase in mast cell degranulation (19.75 ± 3.77% vs. 42.53 ± 0.42%; p < 0.001) and in the levels of reduced glutathione (293.9 ± 19.21 vs. 723.7 ± 67.43 nM/g of tissue; p < 0.05); as well as a significant reduction in mucociliary clearance (p < 0.05), which caused significant changes in pulmonary function (in MIP and MEP; p < 0.05 for both) and airway hyperreactivity. Conclusions: Passive inhalation of cigarette smoke caused significant increases in mast cell degranulation and oxidative stress. This inflammatory process seems to influence the decrease in mucociliary transport and to cause changes in pulmonary function, leading to tracheal hyperreactivity.


1982 ◽  
Vol 52 (3) ◽  
pp. 773-779 ◽  
Author(s):  
S. J. England ◽  
D. Bartlett ◽  
J. A. Daubenspeck

The pattern of respiratory movements of the vocal cords in relation to airflow and respiratory system resistance was assessed in healthy human volunteers during quiet breathing. Motion pictures of the vocal cords were obtained through a fiber-optic laryngoscope inserted transnasally under topical anesthesia. A simultaneous estimate of lung volume was obtained using either rib cage and abdominal magnetometer coils or an integrated pneumotachograph signal. The vocal cords separated during inspiration and moved closer together during the expiratory phase of each breath. The extent of these movements varied greatly among the subjects. Total respiratory system resistance, assessed by the forced oscillation technique, was negatively correlated with distance between the vocal cords when measured at isoflow points in inspiration and expiration. Analysis of breath-by-breath variations in expiratory airflow and vocal cord position revealed that decreases in airflow accompanied decreases in the distance between the vocal cords. The results of this study indicate that the human larynx participates in the regulation of respiratory airflow by providing a variable, controlled resistance.


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