Bronchial effects of alpha 2-adrenoceptor antagonists in asthma.
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Adrenergic alpha-Antagonists↗
Biomedical subjects
J Regnard
Publications and source records attributed to J Regnard.
Intrathoracic airstream temperatures during acute expansions of thoracic blood volume.
1. To determine the validity of employing intrathoracic heat flux as a reflection of changes in bronchial blood flow, we used a thermal probe to record airstream temperatures within the tracheobronchial tree in five normal and five asthmatic subjects during isocapnic hyperventilation challenges with and without inflation of the lower limb bladders of a pressure suit. 2. During hyperpnoea, airstream temperatures fell progressively in both subject groups. When blood volume was acutely shifted from the legs into the thorax via anti-shock trousers, airstream temperatures within the tracheobronchial tree rose and were significantly higher than the temperature recorded during hyperpnoea alone. In the normal subjects, once hyperpnoea ceased, the rate of airway re-warming was similar whether or not the anti-shock trousers were inflated. In the asthmatic subjects, however, shifting blood into the thorax attenuated the obstructive response to hyperpnoea and slowed the rate of re-warming. 3. These data demonstrate that changes in airway blood volume are reflected in fluctuations in intrathoracic heat exchange and that disruption of the end hyperpnoea thermal gradient attenuates the airway obstruction that follows hyperpnoea. Since the bronchial blood supply is the major source of heat to the airways, this circulation may play an important role in thermally induced asthma.
Asthma↗
Decreased bronchial response to methacholine in IDDM patients with autonomic neuropathy.
This study was designed to evaluate the involvement of airways innervation during diabetic autonomic neuropathy. Bronchial response to methacholine was assessed by inhalation of serially doubling doses in 22 insulin-dependent diabetes mellitus (IDDM) patients and 11 nondiabetic control subjects selected for their nonsmoking habits. Cardiovascular autonomic control was studied by four standardized tests, i.e., blood pressure and heart-rate variations during orthostatism, heart-rate variation during Valsalva maneuver, and deep breathing. Magnitude and time-course of response to methacholine were similar in nondiabetic subjects and IDDM patients without any abnormal result on cardiovascular tests. Conversely, bronchial response to methacholine was markedly reduced in IDDM patients with one or more abnormal results by cardiovascular assessment of autonomic control. In the IDDM patients, bronchial response to methacholine was significantly correlated to indexes of cardiovascular autonomic control. These results suggest that, during diabetic neuropathy, innervation of the airways likewise involves cardiac autonomic control and leads to impairment of defense reflexes of the airways.
Adult↗
[Maximal ventilatory pressure through the mouth in adults: normal values and explanatory variables].
Mouth pressure measured during maximal inspiratory or expiratory efforts depends on the force exerted by ventilatory muscles. Normal values and anthropometric factors accounting for maximal inspiratory and expiratory pressures (MIP, MEP) are not fully agreed upon to date. We measured MIP and MEP in 253 normal subjects (135 females and 118 males, age 15-59 years) using a digital transducer (163 Sibelmed). All subjects had normal forced vital capacity (FVC) and one second forced expiratory volume (FEV1). Sex, age, height and weight were recorded for all subjects and were entered as independent variables in computation of linear multiple regressions with MEP or MIP the dependent variables. MEP and MIP were greater in males than in females (p less than 0.01) with MIP lower than MEP in both sexes (p less than 0.01). In both males and females, FVC and FEV1 depend on age and height (p less than 0.01). In the entire group, we found a correlation of MIP in females and MEP in males with age (p less than 0.01) and of both MIP and MEP in females with weight (p less than 0.01). However, in subjects aged 20-59 years, there was no significant dependence of MIP and MEP on age, and when the weight of subjects was normal (n = 170), MIP and MEP were independent of weight. We conclude that in adults aged 20-59 years and with normal weight, maximal ventilatory pressures depend solely on sex. In this subgroup mean (+/- SD) values of MEP and MIP were 111 +/- 25 cmH2O and 79 +/- 19 cmH2O respectively in females and 192 +/- 42 cmH2O and 117 +/- 25 cmH2O in males.
Adolescent↗
Effects of SK&F 104353, a leukotriene receptor antagonist, on the bronchial responses to histamine in subjects with asthma: a comparative study with terfenadine.
We compared the effects of pretreatment of 800 micrograms of inhaled Smith Kline & French (SK&F) 104353, a leukotriene receptor antagonist, and 120 mg of oral terfenadine on the bronchial responses to inhaled histamine in 12 subjects with asthma. The study took place on 3 different days and was conducted according to a double-blind, crossover, double-dummy, randomized, and placebo-controlled design. There was no difference in baseline and prechallenge FEV1 after placebo, SK&F 104353, and terfenadine administration. The median ratio of the provocative dose causing a 20% fall in FEV1 from baseline (PD20) with terfenadine over PD20 with placebo was 12.36 (range, 3.2 to 30.3; p less than 0.01) and that of PD20 with SK&F 104353 over PD20 with placebo was 1.51 (range, 0.8 to 5.9; not significant). Analysis of individual results demonstrated a shift toward the right of the dose-response curves to histamine with SK&F 104353 compared to that with placebo in three subjects, whereas the active compound did not exhibit any protective effect against histamine in the remaining nine subjects. We conclude that there is a leukotriene component to the bronchial responses to histamine in some, but not all, subjects. This component remains, however, small and does not appear to be clinically important in the population of subjects with asthma that was studied.
Adult↗
Inflation of antishock trousers increases bronchial response to methacholine in healthy subjects.
We studied changes in lung volumes and in bronchial response to methacholine chloride (MC) challenge when antishock trousers (AST) were inflated at venous occlusion pressure in healthy subjects in the standing posture, a maneuver known to shift blood toward lung vessels. On inflation of bladders isolated to lower limbs, lung volumes did not change but bronchial response to MC increased, as evidenced by a greater fall in the forced expiratory volume in 1 s (FEV1) at the highest dose of MC used compared with control without AST inflation (delta FEV1 = 0.94 +/- 0.40 vs. 0.66 +/- 0.46 liter, P less than 0.001). Full inflation of AST, i.e., lower limb and abdominal bladder inflated, significantly reduced vital capacity (P less than 0.001), functional residual capacity (P less than 0.01), and FEV1 (P less than 0.01) and enhanced the bronchial response to MC challenge compared with partial AST inflation (delta FEV1 = 1.28 +/- 0.47 liter, P less than 0.05). Because there was no significant reduction of lung volumes on partial AST inflation, the enhanced bronchial response to MC cannot be explained solely by changes in base-line lung volumes. An alternative explanation might be a congestion and/or edema of the airway wall on AST inflation. Therefore, to investigate further the mechanism of the increased bronchial response to MC, we pretreated the subjects with the inhaled alpha 1-adrenergic agonist methoxamine, which has both direct bronchoconstrictor and bronchial vasoconstrictor effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Bronchial hyperresponsiveness to methacholine in patients with impaired left ventricular function.
To elucidate the pathogenesis of bronchospasm in congestive heart failure, we studied 23 patients with chronic impairment of left ventricular function due to coronary artery disease or dilated cardiomyopathy. In 21 of them we found marked bronchial hyperresponsiveness to methacholine. The mean dose (+/- SD) of methacholine that elicited a 20 percent decrease in the forced expiratory volume in one second (FEV1) was 421 +/- 298 micrograms, nearly the same as in patients with symptomatic asthma. In contrast, there was no bronchial response to methacholine in 9 of 10 patients who had coronary artery disease but normal left ventricular function. Administration of the bronchodilator albuterol led to a partial (43 percent) reversal of the methacholine-induced bronchial obstruction. In 12 patients, pretreatment with the alpha-adrenergic agonist methoxamine (10 mg by inhalation), a potent vasoconstrictor, fully prevented the methacholine-induced decrease in FEV1. The protective effect of methoxamine was blocked by the alpha-adrenergic antagonist phentolamine in all six patients who received this agent. We conclude that bronchial hyperresponsiveness to cholinergic agonists is frequent in patients with impaired left ventricular function and may contribute to the wheezy dyspnea commonly observed in such patients. The bronchoconstriction may be mediated at least in part by dilatation of the bronchial vessels.
Adult↗
Ventilatory response to carbon dioxide during extradural anaesthesia with lignocaine and fentanyl.
Twenty-seven patients undergoing extracorporeal shock-wave lithotripsy or knee arthroscopy received extradural anaesthesia with 2% lignocaine plus adrenaline 1 in 200,000. They were allocated randomly to three groups, one receiving no fentanyl (n = 6), the two others receiving fentanyl 50 micrograms either extradurally (n = 15) or i.v. (n = 6). Three tests of sensitivity to carbon dioxide (Read's method) were performed successively on each patient: before operation and at 1 and 2 h after the extradural injection. Whereas lignocaine and adrenaline alone had no significant effects on basal ventilation and the ventilatory response to carbon dioxide, extradural fentanyl caused a slight reduction in resting ventilatory rate and ventilation at 1 and 2 h with no change in resting end-tidal carbon dioxide concentration. In addition, the slope of the ventilatory response to carbon dioxide was reduced slightly at 1 h and ventilation at end-tidal PCO2 of 7.3 kPa was reduced also at 1 and 2 h. Conversely, the same dose of fentanyl i.v. had lesser and shorter effects on ventilation at rest and during carbon dioxide rebreathing. Our results show that fentanyl 50 micrograms given extradurally caused slight ventilatory depression which is probably clinically unimportant.
Adult↗
[Respiratory depressant effect of fentanyl in a small dose (50 g) by peridural injection].
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Anesthesia, Epidural↗
Pretreatment with an inhaled alpha 1-adrenergic agonist, methoxamine, reduces exercise-induced asthma.
In order to assess the role of the bronchial circulation in the pathogenesis of exercise-induced asthma (EIA), we conducted a double-blind, randomized study of the effects of pretreatment with an inhaled alpha 1-adrenergic agonist, methoxamine (Mx), in nine asthmatic teenagers with known EIA. Exercise consisted of 5 min cycle ergometry at a submaximal, constant work-load, while the subjects breathed dry air at ambient temperature. Forced expiratory volume in one second (FEV1) was measured at baseline, 15 min after pretreatment of either Mx or saline, and serially after exercise. Mx significantly reduced the exercise-induced fall of FEV1 without modifying baseline FEV1 in five of the eight subjects, had little or no effect in three and caused an acute asthmatic attack in the remaining subject. Mx has potent constrictor effects on both bronchial and vascular smooth muscles through stimulation of postjunctional alpha 1-adrenoceptors. Therefore, the protective effect of Mx on EIA may be attributed to vasoconstriction of tracheobronchial vessels opposing the hyperaemia and mucosal airway oedema that may cause, at least in part, the exercise-induced acute bronchial obstruction in EIA. Alternatively, Mx stimulates mucus, water and electrolyte secretion by airway epithelium and may, therefore, oppose the dehydration of airway surface that could be a causative factor of EIA.
Administration, Inhalation↗
Comparative effects of rilmenidine and clonidine on bronchial responses to histamine in asthmatic subjects.
1. The effects of pretreatment with clonidine and rilmenidine, a new alpha 2-adrenoceptor agonist, on the bronchial responses to inhaled histamine were studied on 3 different days in a controlled, double-blind, randomized study in 12 asymptomatic asthmatic subjects. Clonidine and rilmenidine were orally administered as single and equipotent doses of 150 micrograms and 1 mg, respectively. All the subjects were non-smokers with normal lung function tests (forced expiratory volume in one second (FEV1) = 97 +/- 10% predicted FEV1). 2. Histamine (first dose = 543 nmol) was delivered by a breath activated dosimeter (DeVilbiss no. 646 nebulizer) every 5 min; FEV1 was measured in triplicate after each dose and the largest value was analyse. The three dose-response curves were compared by analysis of variance. 3. Both clonidine and rilmenidine decreased arterial blood pressure in all subjects. There was no difference in baseline values and pre-challenge values of FEV1 after placebo, clonidine and rilmenidine on the 3 study days. Compared with placebo, both rilmenidine and clonidine significantly increased the bronchial responses to histamine (P less than 0.05 and P less than 0.01 respectively) an effect which was significantly more marked with clonidine than rilmenidine (P less than 0.05). 4. We suggest that the enhancement of bronchial responsiveness to histamine by clonidine and rilmenidine may result from their effects on both central and peripheral alpha 2-adrenoceptors, and that the lesser aggravation of histamine-induced bronchial obstruction in asthmatic subjects on rilmenidine might be explained by its lesser central and/or greater peripheral effects than clonidine.
Adrenergic alpha-Agonists↗
Nasal mucociliary transport in healthy subjects is slower when breathing dry air.
We assessed the effect of dry air (DA) nasal breathing on nasal clearance rate in healthy nonsmoking subjects. We measured saccharin nasal transit time (SNTT), an index of mucociliary clearance rate, in eleven normal subjects (six males, five females) breathing either room air (RA) or DA through the nose in random order on six different study days. On each study day, the trial was conducted at the same time, in the same nostril, using a patent airway. DA was breathed through a light-weight, tight-fitting, nasal mask (SEFAM, France) for 30 min and SNTT was then measured immediately. Saccharin (250 micrograms) was deposited on the anterior part of the inferior turbinate under visual control and saliva was swallowed every 30 s thereafter. SNTT was the time elapsed between deposition and first perception of saccharin taste. The group-average SNTT on DA was 18.5 +/- 8.6 min which was significantly longer than on RA (11.9 +/- 5.3 min). Our findings suggest that dry air breathing results in excessive water loss by the nasal mucosa, which may in turn reduce nasal mucociliary clearance rate through changes in the rheological properties or adhesiveness of nasal mucus and/or slowing of ciliary beating.
Adhesiveness↗
Effects of clonidine on bronchial responses to histamine in normal and asthmatic subjects.
Our aim was to examine the effects of clonidine (C), an agonist of central and peripheral alpha-2 adrenoceptors, on bronchomotor responsiveness to histamine (H). In a double-blind study, we compared on two different days the effects of pretreatment with placebo (P) and with 200 micrograms or 150 micrograms of C given orally, in ten normal (NS) and eight asymptomatic asthmatic subjects (AS) respectively, the response to inhalation of serially increasing doses of H. On each day, five doubling doses of H (first dose = 3.5 and 1.1 mumol in NS and AS, respectively) were administered every 5 min; forced expiratory volume in one second (FEV1) was measured after each dose. The dose-response curves were compared by an analysis of variance. Clonidine caused hypotension with bradycardia in all subjects. Baseline values and pre-challenge values of FEV1 after P and C were identical on the two study days. Compared to P, C did not modify the response to H in NS but significantly increased it in AS (p less than 0.01). Our results suggest that the neural control of the airways differs in AS compared to NS and could be explained either by a decrease in sympathetic inhibitory activity or a greater responsiveness of the airways to parasympathetic stimulation and/or a higher parasympathetic tone in AS.
Asthma↗
The physical characteristics of the members during the International Biomedical Expedition to the Antarctic.
Twelve male medical scientists formed the International Biomedical Expedition to the Antarctic (IBEA). Their physical characteristics and maximum oxygen uptakes (VO2max) were measured in association with three series of thermal tolerance tests in Sydney, twice before and once after going to the Antarctic. In the Antarctic they lived in tents and spent 15 days travelling by motor toboggan. Their body mass (BM) and skinfold thickness (SFT) were measured four times during the 69 days the expedition spent in the field. The characteristics of the group were (ranges): age 26-52 years, height 1680-1889 mm, BM 58.5-103.4 kg, fatness 16-34% BM and VO2max 33-49 ml X kg-1 X min-1. In the Antarctic 9 men lost between 0.7 and 5.5 kg (mean 2.7 kg) of BM with a decrease in SFT, whilst 2 men increased BM by 1.2 and 1.9 kg without change in SFT. One man retired early from the expedition. BM and SFT were regained and physical fitness lost during the return voyage to Australia. Consequently there was no difference in average SFT between the pre- and post-Antarctic laboratory tests, but BM was greater after the Antarctic implying gains in fat free mass. VO2max was lower in the final laboratory tests than in the tests before Antarctica.
Acclimatization↗
Electrophysiological parameters in the male Wistar rat.
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Animals↗
[Measurement of PACO2 in children by capnography and mass spectrometry (author's transl)].
The present study examines the errors of measurement under working conditions using a capnograph and suggests a methodology to obtain optimal results in a given clinical situation. The authors compare the PCO2 measured with the aid of capnograph using CO2 absorption by infrared, with simultaneous measurements of PCO2 using a mass spectrometer as the reference. The observations measured included static and dynamic responses to a step variation of 5% CO2 and also the PACO2 in normal 9 to 12 year old children. The results show that the errors using a capnograph may reach 45 per cent at the highest respiratory frequencies. The influence of the dimensions of the sampling apparatus and the output of the sampling pump on the measurement of PACO2 are discussed. The static and dynamic calibration allow optimal operating conditions for the requirements of a patient in bed. (In this study children aged 9 to 12, with a respiratory frequency of less than 40/min). The errors after achieving optimal conditions is independent of respiratory frequency and always remained less than 5 per cent. A few simple rules are suggested to avoid the errors we have seen and if proper precautions are taken capnography can be considered as a good method for measuring PACO2 in children.
Breath Tests↗
Letter: Indole-negative Escherichia coli strains.
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Escherichia coli↗
Renal transplantation and viral infections. II. Results of follow-up studies.
13 renal transplant recipeints were submitted to virological survey over a period of about 10 months following transplantation. They were compared to a group of individuals who underwent no transplantation : 7 patients on chronic hemodialysis and 10 healthy blood donors. The renal transplant recipients, showed rises in titer of antibodies against various viral antigens. Nevertheless, no other viral elimination but that of cytomegalovirus and herpes simplex virus was detected in them. Renal trnasplant recipients show significantly more often rises in virus antibody titers than the other individuals, when time of survey is taken into account. Some of these rises appeared to be simultaneous. Their mechanism is under debate : analysis of special cases and observation of associated immunohematological abnormalities are strongly suggesting that in some situations, rises in titer of viral antibodies may occur without infection.
Adult↗