Lung mechanics following antigen challenge of Ascaris suum-sensitive rhesus monkeys

1976 ◽  
Vol 41 (5) ◽  
pp. 668-676 ◽  
Author(s):  
P. D. Pare ◽  
M. C. Michound ◽  
J. C. Hogg

Pulmonary resistance (RL) breathing air and a helium-oxygen mixture (He-O2) dynamic compliance (Cdyn), respiratory frequency (f), subdivisions of lung volume, and static deflation pressure-volume (PV) curves were measured before and after bronchial challenge with Ascaris suum antigen in six rhesus monkeys with varying skin reactivity to this antigen. The animals were lightly anesthetized with pentobarbital sodium, intubated, and studied in a volume displacement body plethysmograph, transpulmonary pressure being measured with an esophageal balloon technique. With the animals breathing spontaneously antigen was delivered with a De Vilbiss ultrasonic nebulizer and RL was determined by the method of electrical subtraction. With challenge, three monkeys showed no response and three persistently demonstrated significant bronchonconstriction (peak RL 700+/-100% control) with a decreased response to He-O2 suggesting combined central and peripheral airway narrowing. Responding monkeys also developed tachypnea (f 210+/-8% control) and a fall in Cdyn (18+/-6% control) but no significant changes in total lung capacity and its subdivisions, or in static PV curves were seen. We conclude that this primate model shows important similarities to and differences from human asthma.

2017 ◽  
Vol 123 (5) ◽  
pp. 1188-1194 ◽  
Author(s):  
Catherine E. Farrow ◽  
Cheryl M. Salome ◽  
Benjamin E. Harris ◽  
Dale L. Bailey ◽  
Norbert Berend ◽  
...  

In asthma, bronchoconstriction causes topographically heterogeneous airway narrowing, as measured by three-dimensional ventilation imaging. Computation modeling suggests that peripheral airway dysfunction is a potential determinant of acute airway narrowing measured by imaging. We hypothesized that the development of low-ventilation regions measured topographically by three-dimensional imaging after bronchoconstriction is predicted by peripheral airway function. Fourteen asthmatic subjects underwent ventilation single-photon-emission computed tomography/computed tomography scan imaging before and after methacholine challenge. One-liter breaths of Technegas were inhaled from functional residual capacity in upright posture before supine scanning. The lung regions with the lowest ventilation (Ventlow) were calculated using a thresholding method and expressed as a percentage of total ventilation (Venttotal). Multiple-breath nitrogen washout was used to measure diffusion-dependent and convection-dependent ventilation heterogeneity (Sacin and Scond, respectively) and lung clearance index (LCI), before and after challenge. Forced expiratory volume in 1 s (FEV1) was 87.6 ± 15.8% predicted, and seven subjects had airway hyperresponsiveness. Ventlow at baseline was unrelated to spirometry or multiple-breath nitrogen washout indices. Methacholine challenge decreased FEV1 by 23 ± 5% of baseline while Ventlow increased from 21.5 ± 2.3%Venttotal to 26.3 ± 6.7%Venttotal ( P = 0.03). The change in Ventlow was predicted by baseline Sacin ( rs = 0.60, P = 0.03) and by LCI ( rs = 0.70, P = 0.006) but not by Scond ( rs = 0.30, P = 0.30). The development of low-ventilation lung units in three-dimensional ventilation imaging is predicted by ventilation heterogeneity in diffusion-dependent airways. This relationship suggests that acinar ventilation heterogeneity in asthma may be of mechanistic importance in terms of bronchoconstriction and airway narrowing. NEW & NOTEWORTHY Using ventilation SPECT/CT imaging in asthmatics, we show induced bronchoconstriction leads to the development of areas of low ventilation. Furthermore, the relative volume of the low-ventilation regions was predicted by ventilation heterogeneity in diffusion-dependent acinar airways. This suggests that the pattern of regional airway narrowing in asthma is determined by acinar airway function.


1983 ◽  
Vol 55 (1) ◽  
pp. 92-99 ◽  
Author(s):  
J. M. Hinson ◽  
A. A. Hutchison ◽  
M. L. Ogletree ◽  
K. L. Brigham ◽  
J. R. Snapper

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.


1987 ◽  
Vol 65 (6) ◽  
pp. 1234-1238 ◽  
Author(s):  
John T. Fisher ◽  
Mark A. Waldron ◽  
Craig J. Armstrong

The present study was designed to investigate the effects of hypoxia on lung mechanics in the newborn cat and to determine if vagal efferent innervation to the airways is involved in the response. We studied 11 animals, aged 2–7 days, anesthetized with a mixture of chloralose–urethane administered intraperitoneally. A tracheal cannula was inserted just below the larynx and following paralysis (pancuronium bromide), mechanical ventilation was initiated. A pneumothorax was created by a midline thoracotomy and an end-expiratory load was applied to maintain functional residual capacity. Animals were placed in a flow plethysmograph from which measurements of transpulmonary pressure, flow, and volume, mean inspiratory resistance, and dynamic compliance of the lung were calculated. The experimental protocol consisted of a series of 8-min trials, each preceded by a controlled volume history. The hypoxia challenge was composed of 1 min of ventilation with 40% O2, followed by 5 min exposure to 10% O2 and 2 min of recovery. In the majority of animals (7 out of 11), hypoxia had no effect on lung mechanics compared with control trials. Four animals responded to hypoxia with an increase in resistance and a decrease in compliance. Resistance remained elevated throughout the hypoxia with an average maximal increase of 47.2 ± 22.2% (SD). Dynamic compliance was significantly decreased at the 2nd, 3rd, and 4th min only of hypoxia. Bilateral vagotomy abolished the response in the four animals and hypoxia had no effect on mechanics postvagotomy. Our data suggest that in most cases changes in lung mechanics do not play a causal role in the biphasic ventilatory response to hypoxia seen in the newborn.


2011 ◽  
Vol 110 (5) ◽  
pp. 1400-1405 ◽  
Author(s):  
David G. Chapman ◽  
Norbert Berend ◽  
Gregory G. King ◽  
Cheryl M. Salome

The mechanisms by which deep inspiration (DI) avoidance increases airway responsiveness in healthy subjects are not known. DI avoidance does not alter respiratory mechanics directly; however, computational modeling has predicted that DI avoidance would increase baseline ventilation heterogeneity. The aim was to determine if DI avoidance increased baseline ventilation heterogeneity and whether this correlated with the increase in airway responsiveness. Twelve healthy subjects had ventilation heterogeneity measured by multiple-breath nitrogen washout (MBNW) before and after 20 min of DI avoidance. This was followed by another 20-min period of DI avoidance before the inhalation of a single methacholine dose. The protocol was repeated on a separate day with the addition of five DIs at the end of each of the two periods of DI avoidance. Baseline ventilation heterogeneity in convection-dependent and diffusion-convection-dependent airways was calculated from MBNW. The response to methacholine was measured by the percent fall in forced expiratory volume in 1 s/forced vital capacity (FVC) (airway narrowing) and percent fall in FVC (airway closure). DI avoidance increased baseline diffusion-convection-dependent airways ( P = 0.02) but did not affect convection-dependent airways ( P = 0.9). DI avoidance increased both airway closure ( P = 0.002) and airway narrowing ( P = 0.02) during bronchial challenge. The increase in diffusion-convection-dependent airways due to DI avoidance did not correlate with the increase in either airway narrowing ( rs = 0.14) or airway closure ( rs = 0.12). These findings suggest that DI avoidance increases diffusion-convection-dependent ventilation heterogeneity that is not associated with the increase in airway responsiveness. We speculate that DI avoidance reduces surfactant release, which increases peripheral ventilation heterogeneity and also predisposes to peripheral airway closure.


1975 ◽  
Vol 38 (6) ◽  
pp. 974-982 ◽  
Author(s):  
S. Freedman ◽  
A. E. Tattersfield ◽  
N. B. Pride

Pulmonary and airway mechanics were assessed in seven asthmatic patients in remission, when asthma was induced by exercise and again after spontaneous recovery or bronchodilator treatment. After exercise there was a sustained fall in forced expiratory volume in 1 s (FEV 1.0) in all patients, varying from 30 to 80 percent of the initial value. Total lung capacity (TLC) increased significantly in four of the seven patients. In one of the four patients the increase in TLC was associated with an increase in static transpulmonary pressure at full inflation but in the remaining three patients it was associated with a parallel shift of the pressure-volume curve of the lung without change in its slope. In all patients residual volume increased, regardless of change in TLC; both pressure-volume and maximum expiratory flow-volume curves suggested that widespread airway closure (or virtual closure) occurred at positive transpulmonary pressures when asthma was induced. Loss of lung recoli pressure sometimes contributed to the reduction in maximum expiratory flow but diffuse airway narrowing was probably the dominant abnormality. When air-flow obstruction became more severe the ratio of expiratory to inspiratory time was increased and although expiratory flow limitation was present excessive expiratory pressures were not generated.


1979 ◽  
Vol 46 (1) ◽  
pp. 61-66 ◽  
Author(s):  
A. G. Haddad ◽  
R. L. Pimmel ◽  
D. D. Scaperoth ◽  
P. A. Bromberg

Respiratory mechanics were studied in nine intubated dogs before and after exposure to aerosolized papain under conditions known to produce emphysemalike lesions. Forced oscillatory resistance (RFO), compliance (CFO), and inertance (IFO) were computed from impedance data obtained at transrespiratory pressures of -10, 0 (FRC), +10, and +20 cmHWO. Dynamic compliance during tidal breathing (CTB) was also measured at FRC. After papain exposure CTB and CFO increased by 25% (P less than 0.05) at FRC and at +10 cmH2O. There were no consistent changes in RFO or IFO at FRC. However, RFO showed a greater dependency on transrespiratory pressure, which suggests that the elastic properties of airways may also have been affected by papain. Measurements made in open-chested papain-exposed animals showed that about 17% of total RFO and 20% of total elastance were attributable to the chest wall. Forced oscillatory impedance data are sensitive to experimental changes in lung mechanics and provide useful estimates of standard respiratory parameters.


1978 ◽  
Vol 44 (2) ◽  
pp. 150-155 ◽  
Author(s):  
R. Brown ◽  
R. H. Ingram ◽  
E. R. McFadden

Prostaglandins have been implicated as secondary pharmacologic mediators in allergic bronchial asthma. We have studied the effects of the intravenous infusion of prostaglandin F2alpha (PGF2alpha) on pulmonary mechanics in nonasthmatic and asthmatic volunteers. Before and during the infusion, measurements were made of total lung capacity and its subdivisions, static deflational transpulmonary pressure-volume relationships (PV), and maximal expiratory flow-volume curves with air and after a washing of an 80% helium-20% oxygen mixture. In both groups, PGF2alpha caused significant decreases in vital capacity and maximal flow and increases in residual volume. There were not significant differences between groups in either the absolute magnitude or the percent change in the variables, a result which may have been due to the similarity of the pulmonary mechanics in both groups prior to infusion. Changes in density dependence were bidirectional in both groups, indicating that relative contributions of large and small airways to flow limitation changed differently among individuals. The single between-group difference in responses noted was a leftward shift of the PV curve in the asthmatics, suggesting recoil of the lung which occurs in asthma.


1996 ◽  
Vol 80 (6) ◽  
pp. 1872-1879 ◽  
Author(s):  
T. Nagase ◽  
H. Matsui ◽  
E. Sudo ◽  
T. Matsuse ◽  
M. S. Ludwig ◽  
...  

It has been reported that both the elasticity of the cartilage and airway-parenchymal interdependence can modify shortening of the airway smooth muscle and airway narrowing during induced constriction. We hypothesized that induced softening of the cartilage could alter airway compliance and/or the forces of mechanical interdependence, resulting in an increased degree of airway narrowing in response to a contractile stimulus. To test this hypothesis, we compared the effects of changing lung volume on airway resistance (Raw) under baseline conditions and during methacholine (MCh)-induced constriction in papain-treated (n = 6) and control rabbits (n = 6). With use of the alveolar capsule technique, Raw was directly measured under baseline conditions at different levels of end-expiratory transpulmonary pressure (Ptp = 4-12 cmH2O). Then aerosolized MCh was delivered (0.2-25 mg/ml) and measurements were performed at different levels of Ptp (4 and 12 cmH2O). From measured tracheal flow and tracheal and alveolar pressure in open-chest animals during mechanical ventilation (tidal volume = 6 ml/kg, breathing frequency = 1 Hz), we calculated Raw by subtracting tissue resistance from lung resistance. Papain treatment significantly increased Raw both under baseline conditions and after induced constriction. We found that increasing Ptp decreased Raw before and after MCh in both groups; however, the effects of changing Ptp on Raw were less in papain-treated animals. These observations suggest that both cartilage elasticity and mechanical interdependence are important determinants of airway smooth muscle shortening. The observation that volume dependence of Raw was less in papain-treated animals is consistent with the hypothesis that papain effects significant changes in the parenchymal attachments.


1987 ◽  
Vol 63 (4) ◽  
pp. 1544-1550 ◽  
Author(s):  
G. G. Weinmann ◽  
Y. C. Huang ◽  
W. Mitzner

The different tidal volumes and frequencies of high-frequency ventilation (HFV) compared with conventional mechanical ventilation (CMV) may have different effects on lung mechanics. To test this hypothesis, we compared the effects of 3 h of HFV and CMV on total lung capacity (TLC), functional residual capacity (FRC), the shape of the pressure-volume (PV) curve (%V10), and dynamic compliance (Cdyn), as well as venous admixture and alveolar-arterial O2 gradient. We studied a total of 12 dogs at lung inflations equivalent to 15 cmH2O positive end-expiratory pressure (PEEP) (group I) and 8 dogs at lung inflations equivalent to 0 cmH2O PEEP (group II). For CMV, we used a standard-volume ventilator at a mean tidal volume of 13.8 ml/kg. For HFV, we used an oscillator-type ventilator at 15 Hz and an average tidal volume of 4.3 ml/kg. Our results showed that ventilation with 3 h of PEEP raised lung volume, and lung volumes on HFV were higher than those on CMV in both groups. Specifically, in group I, the volume during ventilation rose on both CMV (150 ml) and HFV (250 ml). These volume changes persisted beyond the ventilation period, such that TLC was unchanged on CMV but had risen 200 ml on HFV. FRC also rose 200 and 300 ml after HFV and CMV, respectively. In group II, the volume during ventilation fell 100 ml on CMV and rose slightly (40 ml) on HFV. TLC and FRC both tended to fall more on CMV.(ABSTRACT TRUNCATED AT 250 WORDS)


1981 ◽  
Vol 51 (4) ◽  
pp. 806-811 ◽  
Author(s):  
S. H. Loring ◽  
R. H. Ingram ◽  
J. M. Drazen

The pulmonary effects of aerosol histamine exposure include an increase in pulmonary resistance (RL) and a decrease in dynamic compliance (Cdyn). These changes are substantially reversed by inflation of the lungs to 30 cmH2O transpulmonary pressure (TLC). Although histamine has been shown to change both the airway and tissue components of RL and Cdyn, it is not known whether lung inflation reverses the changes in airways, in tissue, or in both. We studied six anesthetized, paralyzed, open-chest dogs. We sequentially measured RL and Cdyn during oscillations in lung volume at 0.6 Hz with the airway open and during compression-decompression of the lungs without tracheal airflow. In the control state after saline aerosol, inflation to TLC resulted in a slight increase in compliance and a decrease in the tissue component of RL. Aerosol histamine exposure caused an increase in resistance and a decrease in compliance due to both airway and tissue changes. Inflation of the lungs to TLC largely reversed the changes due to airway constriction without consistently affecting the changes due to tissue. We conclude that after histamine exposure smooth muscle responsible for airway narrowing is stretched by lung inflation but that contractile elements responsible for alterations in air-space distensibility and hysteresis of dynamic lung recoil are either not stretched by lung inflation or are stretched and shorten again rapidly.


Sign in / Sign up

Export Citation Format

Share Document