Biomedical subjects

J G Martin

Publications and source records attributed to J G Martin.

At least 109 records · Page 6Linked to original sources

PubMed1993

Comparative study of mechanical interdependence: effect of lung volume on Raw during induced constriction.

The mechanical load imposed by the parenchyma can decrease the magnitude of agonist-induced airway constriction. To examine whether variability in mechanical interdependence could account for differences in airway narrowing among different species, we compared the effects of changing lung volume on airway resistance (Raw) under baseline conditions and during methacholine (MCh)-induced constriction in rats and guinea pigs. Direct measurements of Raw were made under baseline conditions at different levels of end-expiratory transpulmonary pressure (PL = 3-11 cmH2O). Then aerosolized MCh was delivered (128 mg/ml in rats, 8 mg/ml in guinea pigs), and measurements were obtained at different levels of PL (3-11 cmH2O). We measured tracheal flow and tracheal and alveolar pressure (using alveolar capsules) in open-chest animals during mechanical ventilation (tidal volume 6 ml/kg, frequency 1 Hz) and calculated Raw by subtracting tissue from total lung resistance. For interspecies comparisons, data were standardized using percent change in Raw (delta % Raw) at PL of 3 cmH2O during baseline and, after MCh, log-scaled delta % Raw at PL of 3 cmH2O. We found that increasing lung volume decreased Raw both at baseline and after MCh in both species. However, changes were far smaller in guinea pigs. During baseline, the slope of the delta % Raw/delta PL was -3.37 and -12.48 %/cmH2O for guinea pigs and rats, respectively (P < 0.001). After MCh, the slope of delta log %Raw/delta PL was -0.065 and -0.154 cmH2O-1 for guinea pigs and rats, respectively (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

PubMed1993

Leukotrienes in bile during the early and the late airway responses after allergen challenge of sensitized rats.

The Brown Norway rat produces high levels of IgE in response to active immunization and develops both early and late airway constrictor responses after subsequent allergen challenge. We have used this model of allergic asthma to investigate the temporal relationship between the in vivo synthesis of peptidoleukotrienes (peptido-LTs) and the late response. Brown Norway rats that had been sensitized by injection of ovalbumin 2 to 3 wk prior to the commencement of the experiment were subjected to bile duct cannulation and tracheal intubation. The rats were challenged 2 h later by intratracheal instillation of ovalbumin. Lung resistance was measured before and at frequent intervals after antigen challenge. Biliary peptido-LTs (LTC4, LTD4, LTE4, and N-acetyl-LTE4) were measured by a combination of high pressure liquid chromatography and radioimmunoassay in bile samples collected for a period of 1 h before instillation of ovalbumin, and between zero and 1 h, 1 and 4 h, 4 and 6 h, and 6 and 8 h, subsequently. All of the 10 rats subjected to antigen challenge developed early responses. Of these, six also developed late responses, whereas two died about 1 h after challenge. The levels of peptido-LTs excreted in bile between 4 and 8 h after antigen challenge (corresponding in time to the late responses) were about four times higher in the ovalbumin-instilled rats that developed late responses (n = 6) than in the ovalbumin-sensitized control rats that had been subjected to instillation of saline (n = 6; p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

PubMed1993

Inflammatory cell populations in the airways and parenchyma after antigen challenge in the rat.

We examined the effects of sensitization and antigen challenge on the cellular populations retrieved from the large airways (LA) (generations zero to 5 approximately) and small airways and parenchyma (S/P) of the rat. Male Brown-Norway rats, 7 to 8 wk of age, were either actively sensitized to ovalbumin (n = 24) or sham-sensitized to saline (n = 9), and, 14 days later, they were anesthetized with urethane, intubated endotracheally, and challenged. Aerosols of ovalbumin (5% wt/vol in saline for 5 min) or saline were administered to 12 and six rats, respectively, and measurements of pulmonary resistance (RL) were made for 8 h. The early airway response (ER) was calculated as the highest value of RL in the first hour after challenge, and the late response (LR) was calculated as an increase in RL to greater than 200% of the baseline value in the 4- to 8-h period after challenge. Rats were killed by exsanguination, LA were separated from S/P, and cells were isolated after tissue mincing and digestion with collagenase. Total and differential cell counts and lymphocyte subsets were determined. Antigen challenge significantly increased the cellular yield (mostly neutrophils) from the LA and S/P. Animals with a LR had a lower total cellular yield from the LA and S/P than did animals without a LR. The animals with a LR also had a lower yield of eosinophils and lymphocytes from the S/P than did animals challenged with saline alone. Cellular yields were not lower in the animals with an isolated ER after antigen challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

PubMed1993

Role of leukotriene D4 in allergen-induced increases in airway smooth muscle in the rat.

The purpose of the study was to investigate whether allergen-induced hyperresponsiveness to methacholine and an increase in airway smooth muscle (ASM) in Brown Norway (BN) rats could be mediated by LTD4, an important mediator of allergic airway responses. Male BN rats, 8 to 12 wk of age, were sensitized with ovalbumin (OA). Rats were exposed 2 wk later to aerosols of saline (n = 6), OA (n = 8), or OA after pretreatment with the LTD4 antagonist MK-571 (2 mg/kg intraperitoneally, n = 9), on six occasions at 5-day intervals. Airway responsiveness to methacholine (the concentration required to double pulmonary resistance, EC200 RL) was measured immediately before the first aerosol exposure and 2 days after the last exposure. ASM was quantitated by morphometry, and areas were standardized for size using the epithelial basement membrane length (BM). Following OA challenges EC200 RL decreased from 6.5 to 3.1 mg/ml (p < 0.05) but did not change significantly after saline or OA exposures in MK-571-pretreated animals. ASM/BM2 in the large airways was significantly greater, 3.41 +/- 0.19 x 10(-3), after OA compared with 2.35 +/- 0.22 x 10(-3) for saline exposures (p < 0.01). The ASM/BM2 after OA exposures but with MK-571 pretreatment (2.75 +/- 0.25 x 10(-3)) was intermediate in value. The results indicate that both the increase in airway responsiveness and the increase in ASM following repeated antigen exposures appear to be mediated predominantly by LTD4.

Airway Resistance↗

PubMed1993

Effect of dexamethasone on airway inflammation and responsiveness after antigen challenge of the rat.

The purpose of this study was to examine the effects of dexamethasone on airway responsiveness and lung inflammation of rats at 8 h, 32 h, and 7 d after allergen challenge. Brown-Norway male rats, 7 to 8 wk old, were actively sensitized to ovalbumin (OA) and challenged 14 d later. The rats were divided into a control group (n = 31) and a test group (n = 34) that received dexamethasone (DEXA) (0.3 mg/kg intraperitoneally) 14 h and 2 h before saline or OA challenge. For challenge, rats were anesthetized with pentobarbital and intubated endotracheally. Aerosols of OA (5% wt/vol in saline) were administered for 5 min. Responsiveness to inhaled aerosols of methacholine and the total and differential leukocyte counts in the large airways (generations 0 to 5), small airways, and parenchyma isolated by tissue mincing and digestion were measured at 8 h, 32 h, and 7 d after OA challenge. The cellular influx into the airways and parenchyma was highest at 8 h and decreased progressively over 7 d. DEXA significantly inhibited the cellular influx after allergen challenge. At 8 h, cellular return from the large airways was 3.61 +/- 0.5 x 10(6) (controls) versus 1.0 +/- 0.2 x 10(6) (DEXA), and from the small airways and parenchyma was 31.7 +/- 2.8 x 10(6) (controls) versus 21.9 +/- 2.9 x 10(6) (DEXA) (p < 0.05). The differences were attributable mostly to decreases in neutrophils in DEXA-treated animals. In control animals, neutrophil yield fell between 8 and 32 h, whereas eosinophils and 32 h, whereas eosinophil and lymphocyte counts increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

PubMed1993

Depletion of OX-8 lymphocytes from the blood and airways using monoclonal antibodies enhances the late airway response in rats.

Recent evidence supports a role for T lymphocytes in allergic airway responses. We hypothesized that reducing blood T suppressor cells (Ts) might increase the late airway response (LR). Sprague-Dawley (SD) rats were sensitized with ovalbumin (OA). On days 8, 10, and 12, post-sensitization test SD (n = 14) received monoclonal antibody intravenously (OX-8; 1 mg) specific to rat Ts. Controls received saline (n = 7) or mouse ascites IgG (n = 7). On day 14, animals were challenged with OA aerosol (5% wt/vol) for 5 min, lung resistance was recorded for 8 h (n = 18) and bronchoalveolar lavage was performed. The LR was determined from the area under the lung resistance vs time curve from 75 to 480 min after challenge. In the remaining 10 rats, airway lymphocyte subsets were measured 8 h after OA aerosol challenge in minced and digested lungs. A decrease in percentage of blood and airway Ts, respectively, in test animals was observed vs controls (blood: 6.27 +/- 0.84 vs 32.95 +/- 1.94, P < 0.001); (airway: 5.05 +/- 0.66 vs 24.5 +/- 3.05, P < 0.02). Blood and airway helper T lymphocytes did not differ between test and control animals. The LR was significantly increased in test (22.89 +/- 3.92) vs controls (4.22 +/- 2.18, P < 0.001). Bronchoalveolar lavage macrophages, neutrophils and lymphocytes, and serum OA-specific IgE were also significantly elevated (P < 0.05) in test animals. We conclude that Ts play an important role in attenuating the LR in SD rats.

Aerosols↗

PubMed1992

Effect of negative pressure ventilation in severe chronic obstructive pulmonary disease.

The hypothesis that patients with chronic obstructive pulmonary disease (COPD) have chronic inspiratory muscle fatigue was tested in an effectiveness trial in which negative pressure ventilation (NPV) was used to produce inspiratory muscle rest. In a double-blind study 184 patients with severe COPD were randomly allocated active or sham NPV treatment for a 12-week period of home use. The distance walked in a 6 min walk test was the primary outcome variable. Secondary outcome measures were cycle exercise endurance time, severity of dyspnoea, quality of life, arterial blood gas tensions, and respiratory muscle strength. The percentage reduction in amplitude of the diaphragmatic electromyographic signal multiplied by hours of NPV was used to reflect the dose of NPV so we could examine dose-response relations. Analysis was based on intention to treat. We found no evidence of a clinically or statistically significant difference in any outcome measure between active and sham groups. No dose-response relation was observed. Moreover, the intervention was poorly accepted despite substantial clinical support. We conclude that NPV as used in this study is difficult to apply and ineffective when used with the aim of resting the respiratory muscles in patients with stable COPD.

Aged↗

PubMed1992

Effects of ketotifen on airway responses to allergen challenge in the actively sensitized brown Norway rat.

The purpose of the study was to examine the effect of ketotifen on the airway responses and the recruitment of the inflammatory cells into the airways of sensitized rats after antigen challenge. Twenty-five Brown Norway rats, 7-9 weeks old, were actively sensitized to ovalbumin (OA) (1 mg s.c.) and Bordetella pertussis vaccine (10(9) bacilli i.p.). At 14 days after sensitization rats were anesthetized with urethane (1.1 g/kg i.p.) and intubated endotracheally. Aerosols of OA (5% W/V in saline for 5 min) were administered to control rats (Group A; n = 9), to a low-dose ketotifen group (Group B; 1 mg/kg PO; n = 8) and a high-dose ketotifen group (Group C; 10 mg/kg; PO for 10 days; n = 9). Pulmonary resistance (RL) was measured at baseline, and every 15 min for up to 8 h after OA. The magnitude of the early response was 241 +/- 51% in A (% baseline RL; mean +/- SE), and significantly less in B(119 +/- 7%) and C(131 +/- 16%) (p < 0.01). The late response was significantly lower in C than A but not B. The total cell number in bronchoalveolar lavage at 8 h after OA challenge was significantly higher in A than B and C (p < 0.01). The lymphocyte and eosinophil counts were reduced in B and C compared to A (p < 0.05). A positive correlation was found between the late response and total number of cells recovered in the BAL (r = 0.78) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

PubMed1992

Effects of prostaglandin E2 on ganglionic transmission in the guinea pig trachea.

We studied the effects of prostaglandin E2 (PGE2) on the contractile responses of in vitro guinea pig tracheal preparations with intact vagal innervation. The preparation was stimulated either through the vagal nerves (NS) or with an electrical field (EFS) and trachealis response was assessed from the pressure change inside the tracheal tube. Ganglionic blockade by hexamethonium inhibited responses to NS but did not affect EFS while both responses to NS and EFS were abolished by atropine or tetrodotoxin. This indicates that responses to both stimulation modalities were mediated by cholinergic nerves but that NS involved a ganglionic relay whereas EFS did not. Within the frequency range of 0.1-20 Hz, there was a gradual increase in the pressure generated by the trachealis muscle with increasing frequency of stimulation. The frequency-response relationship was similar for NS and EFS. Thus, the ganglion does not appear to play an important filtering or amplifying role under those conditions. PGE2 (1-50 mM) produced a concentration-dependent inhibition of NS and EFS without affecting responses to exogenous acetylcholine (ACh). This suggests that the main action of PGE2 is to reduce ACh release from post-ganglionic nerve terminals. PGE2 inhibited EFS to a larger extent than NS; we postulate a possible excitatory effect of PGE2 on neurotransmission in the airway ganglia.

Animals↗

PubMed1992

The relationship between late asthmatic responses and antigen-specific immunoglobulin.

The aim of this study was to examine the relationships between allergen-induced early and late airway responses and antigen-specific IgE, IgG, and lymphocyte subsets in blood and bronchoalveolar lavage (BAL). Brown Norway rats were sensitized at 7 weeks of age with ovalbumin (1 mg s.c.) with use of Bordetella pertussis as an adjuvant. Three weeks after sensitization, animals were anesthetized and challenged with an aerosol of ovalbumin (5% wt/vol in saline) for 5 minutes. Each animal was studied for 8 hours with repeated measurements of lung resistance. Blood was obtained at 0, 1, 2, and 3 weeks before ovalbumin challenge. Ovalbumin-specific IgE and IgG were determined by ELISA. No specific antibody was detectable before sensitization. Ovalbumin-specific IgE and IgG rose between 1 to 2 weeks after sensitization and peaked at 3 weeks. The IgE level did not correlate with the magnitude of either the early or the late responses. In a similar manner no correlation existed between the magnitude of specific IgG and the late response. However, a significant inverse correlation (r = -0.73; p < 0.01) occurred between specific IgG and the early response. No correlation occurred between the ratio of helper (W3/25 +) to suppressor (OX-8 +) lymphocytes in blood and BAL and airway responses to allergen. The size of the early and late responses were correlated, suggesting a common stimulus. Despite the blunting of the early response by repeated sensitization the late response was unaffected, suggesting that the factors that determine the physiologic expression of the early and late responses are different.

Animals↗

PubMed1992

Ice Nucleation Activity in Fusarium acuminatum and Fusarium avenaceum.

Twenty fungal genera, including 14 Fusarium species, were examined for ice nucleation activity at -5.0 degrees C, and this activity was found only in Fusarium acuminatum and Fusarium avenaceum. This characteristic is unique to these two species. Ice nucleation activity of F. avenaceum was compared with ice nucleation activity of a Pseudomonas sp. strain. Cumulative nucleus spectra are similar for both microorganisms, while the maximum temperatures of ice nucleation were -2.5 degrees C for F. avenaceum and -1.0 degrees C for the bacteria. Ice nucleation activity of F. avenaceum was stable at pH levels from 1 to 13 and tolerated temperature treatments up to 60 degrees C, suggesting that these ice nuclei are more similar to lichen ice nuclei than to bacterial ones. Ice nuclei of F. avenaceum, unlike bacterial ice nuclei, pass through a 0.22-mum-pore-size filter. Fusarial nuclei share some characteristics with the so-called leaf-derived nuclei with which they might be identified: they are cell free and stable up to 60 degrees C, and they are found in the same kinds of environment. Highly stable ice nuclei produced by fast-growing microorganisms have potential applications in biotechnology. This is the first report of ice nucleation activity in free-living fungi.

Journal Article↗

PubMed1992

Induction of sleep apnoea with negative pressure ventilation in patients with chronic obstructive lung disease.

BACKGROUND: Negative pressure ventilation provides intermittent non-invasive ventilatory assistance for patients with advanced chronic obstructive lung disease. Upper airway obstruction during sleep, a reported complication of the technique, may, however, limit its clinical applicability. METHODS: The effects of nocturnal negative pressure ventilation on ventilation and on indices of sleep quality were investigated in five patients with severe chronic obstructive lung disease (mean (SE) FEV1 31% (3%) predicted) who had completed three months of nightly negative pressure ventilation. Subjects underwent overnight polysomnography on consecutive nights, the first night serving as a control and negative pressure ventilation being provided on the second night. Ventilators were adjusted to result in maximum suppression of the peak phasic electromyogram signal from the diaphragm. RESULTS: Negative pressure ventilation resulted in substantial increases in episodes of obstructive apnoea and hypopnoea (mean (SE)/h 59.3 (19.8) v 3.2 (1.3) on control nights). Most obstructive events, however, were associated with under 3% oxygen desaturation, and the lowest recorded values for overnight oxygen saturation were similar on the two study nights. Negative pressure ventilation was also associated with significant increases in the frequencies of movement arousals and changes in sleep stage. CONCLUSIONS: Negative pressure ventilation applied during sleep to patients with advanced chronic obstructive lung disease may result in the development of recurrent episodes of apnoea and hypopnoea as well as altered sleep quality, which could limit its clinical applicability.

Aged↗

PubMed1992

In vivo airway reactivity: predictive value of morphological estimates of airway smooth muscle.

Airway responsiveness to methacholine and other bronchoconstrictors is highly variable within and among species. The aim of the experiments in this report was to evaluate the importance of the quantity of airway smooth muscle as a determinant of intra- and inter-species variability in airway responsiveness. To do this we established concentration-response curves to methacholine in a sample of normal guinea pigs as well as in rat, rabbit, and dog. After challenge we excised the lungs for the quantitation of smooth muscle by morphometry. Animals were anesthetized with pentobarbital and mechanically ventilated using a Harvard ventilator. Aerosols of methacholine were administered in progressively doubling concentrations from 0.0625 to 256 mg/mL for a period of 30 s for each concentration. The maximal response, determined from pulmonary resistance (RL), and the concentration of methacholine required to effect 50% of the maximal RL were determined. After provocation testing the lungs were removed and fixed with 10% Formalin. Midsagittal sections and parahilar sections were stained with hematoxylin-phloxine-saffron for microscopic examination of smooth muscle. The images of all airways in the sections were traced using a camera lucida side-arm attachment and digitized using commercial software. The area of the airway wall occupied by smooth muscle was determined and standardized for airway size by dividing it by the square of the epithelial basement membrane length. The variability in airway smooth muscle in the intraparenchymal airways was significantly greater between than within individual guinea pigs (n = 13). This was not true of extraparenchymal airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Low-frequency pulmonary impedance in rabbits and its response to inhaled methacholine.

We assessed pulmonary mechanics in six open-chest rabbits (3 young and 3 adult) by the forced oscillation technique between 0.16 and 10.64 Hz. Under control conditions, pulmonary resistance (RL) decreased markedly between 0.16 and 4 Hz, after which it became reasonably constant. Measurements of alveolar pressure from two alveolar capsules in each rabbit showed that the large decrease of RL with increasing frequency below 4 Hz was due to lung tissue rheology and that tissue resistance was close to zero above 4 Hz. Estimates of resistance and elastance, also obtained by fitting tidal ventilation data at 1 Hz to the equation of the linear single-compartment model, gave values for RL motion that were slightly higher than those obtained by forced oscillations at the same frequency, presumably because of the flow dependence of airways resistance. After treatment with increasing doses of aerosolized methacholine, RL and pulmonary elastance between 0.16 and 1.34 Hz progressively increased, as did the point at which the pulmonary reactance crossed zero (the resonant frequency). The alveolar pressure measurements showed the lung to become increasingly inhomogeneously ventilated in all six animals, whereas in the three younger rabbits lobar atelectasis developed at high methacholine concentrations and the alveolar capsules ceased to communicate with the central airways. We conclude that the low-frequency pulmonary impedance of rabbits exhibits the same qualitative features observed in other species and that it is a sensitive indicator of the changes in pulmonary mechanics occurring during bronchoconstriction.

Administration, Inhalation↗

PubMed1992

A peptidergic component to vagally induced tracheal vasodilation in the dog.

The purpose of the study was to determine the extent that peptidergic afferent and efferent pathways contribute to vagally induced vasodilation in the trachea of the dog. The change in vascular resistance of the tracheal branch of the cranial thyroid artery and the trachealis responses were determined in 28 anesthetized, paralyzed, and mechanically ventilated dogs. After propranolol (2 mg/kg) and phentolamine (1.5 mg/kg), stimulation of the superior laryngeal nerves (NS; 15 Hz, 7 V, 2 ms, 30 s) caused a decrease in vascular resistance of 11.7 +/- 0.8% and a tracheal contraction of 5.2 +/- 4.7 cmH2O. Atropine (1.5 mg/kg) reduced the fall in vascular resistance to 4.7 +/- 0.8% (P less than 0.01), whereas tracheal contraction was abolished. Thiorphan (1.5 mg), a neutral endopeptidase inhibitor, augmented the decrease in vascular resistance (8.8 +/- 0.6%; P less than 0.01) to NS. After hexamethonium (0.5 mg/kg), NS still caused a small decrease in TVR (2.9 +/- 0.9%; P less than 0.05), which was abolished by capsaicin. In atropinized dogs, capsaicin reduced the fall in vascular resistance after NS; the residual vasodilation was virtually abolished by hexamethonium. Acetylcholine (10(-3) mg/kg) decreased vascular resistance (15.7 +/- 3.0%), and the effect was abolished by atropine. We conclude that there is noncholinergic nonadrenergic vagally induced tracheal vasodilation that is peptidergic. The peptidergic vasodilation appears to be mediated by both afferent and efferent pathways.

Acetylcholine↗

PubMed1992

Comparison of upper and lower airway responses of two sensitized rat strains to inhaled antigen.

The purpose of the study was to investigate the relationships between upper airways responses and pulmonary responses of two strains of highly inbred rats to inhaled antigen. To do this we measured the upper and lower airways resistance for 60 min after challenge of Brown-Norway rats (BN; n = 13) and an inbred rat strain (MF; n = 11), derived from Sprague-Dawley, with aerosolized ovalbumin (OA). Rats were actively sensitized with OA (1 mg sc) using Bordetella pertussis as an adjuvant. Two weeks later the animals were anesthetized and challenged. Tracheal pressure, esophageal pressure, and airflow were measured, from which total pulmonary resistance was partitioned into upper airway and lower pulmonary resistance (RL). The peak upper airway response to inhaled OA was similar in BN (1.89 +/- 0.66 cmH2O.ml-1.s; n = 7) and MF (2.85 +/- 0.68 cmH2O.ml-1.s; n = 6). The lower airway response to OA challenge was substantially greater in BN, and RL changed from 0.07 +/- 0.01 to 0.34 +/- 0.13 (n = 6; P < 0.05). The MF did not have any significant increase in RL after challenge; the baseline RL was 0.12 +/- 0.02 and only reached a peak value of 0.15 +/- 0.05 (n = 5; P = NS). Lower airway responsiveness of BN (n = 10) to serotonin, an important mediator early allergic airway responses, was similar to MF (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1992

Effect of body posture on concentration-response curves to inhaled methacholine.

Lung volume has been shown to be a major determinant of the bronchoconstrictor response to inhaled methacholine (MCh). Because a change in body posture from sitting to supine is associated with a reduction in lung volume, we hypothesized that airway responsiveness to inhaled MCh should be affected by body posture. Responsiveness to MCh was assessed in both sitting and supine postures on separate days in 10 subjects aged 24 to 42 yr. Subjects inhaled aerosols of saline and MCh in progressively doubling concentration (0.125 to 256 mg/ml). Responses were assessed by measuring partial and complete forced expiratory flow-volume curves (PEFV and MEFV, respectively). As indices of airway responsiveness, we took the MCh concentration ([MCh]) at which the FEV1 fell by 10% relative to postsaline (PC10), the maximal percentage fall in FEV1 (MR), the [MCh] at which FEV1 reached 50% of MR (EC50), and the [MCh] at which the flow at 20% vital capacity on PEFV curves fell by 20% relative to postsaline (FP20). Responsiveness to MCh was increased in the supine compared with the sitting posture. In the sitting posture, the geometric mean values of MR, PC10, and FP20 were 16.3%, 16.3 mg/ml, and 2.0 mg/ml; supine they were 29.9% (p less than 0.009), 3.0 mg/ml (p less than 0.02), and 0.6 mg/ml (NS), respectively. EC50 did not change with posture. These results are consistent with the notion that airway responsiveness is influenced by airway-parenchymal interdependence and indicate that the results of bronchial provocation testing in the supine posture cannot be directly compared with those in the upright posture.

Adult↗

PubMed1992

Effect of interleukin-2 on the airway response to antigen in the rat.

To evaluate the hypothesis that lymphocyte stimulation can modify the bronchoconstrictive response to inhalational challenge with an allergen, we administered interleukin-2 (IL-2), an important lymphokine in lymphocyte activation and proliferation, to actively sensitized rats. Brown Norway rats received either human recombinant IL-2 (n = 8) or its vehicle (n = 7) twice a day from the ninth to the fourteenth day after active sensitization to ovalbumin (OA) and were challenged with an aerosol of OA. Lung resistance (RL) during the early response increased to a maximum of 698 +/- 230% and 180 +/- 26% of baseline values in the animals receiving IL-2 and vehicle, respectively (p less than 0.025). The late response was threefold greater in IL-2-treated than in vehicle-treated animals (p = 0.01). IL-2 increased OA-specific IgG levels in the serum, but it did not significantly affect total or specific IgE levels. IL-2 caused an inflammatory infiltrate around the airways with significant increases in eosinophils, lymphocytes, and mast cells prior to antigen challenge. Our results indicate that stimulation of cell-mediated immunity can affect airway responsiveness to antigen.

Animals↗