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Biomedical subjects

A Lockhart

Publications and source records attributed to A Lockhart.

At least 109 records · Page 6Linked to original sources
PubMed1989

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↗
PubMed1988

[Exercise-induced asthma].

Exercise-induced asthma only differs from common asthma in its causative factor. It is a typical asthmatic attack which follows a strenuous and continuous physical exercise lasting 5 to 10 minutes, most often in cold and dry weather. The prevalence of exercise-induced asthma has not yet been firmly established; its pathophysiological mechanisms are still debated, and the respective roles of heat and water losses by the airways are not clearly defined. However, the influence of the type of exercise as a precipitating factor of exercise-induced asthma is now well-known. All things being equal, swimming generates less asthma than running and cycling. This enables the subjects to be directed towards the most suitable sports and encouraged to improve their physical fitness. Drug treatment of exercise-induced asthma must preferentially be preventive; it relies on cromoglycate and beta-2 adrenergic agonists, the latter being also capable of treating acute exercise-induced bronchial obstruction. Education of the patients and their family is also important.

Adrenergic beta-Agonists↗
PubMed1988

Effect of theophylline on gastroesophageal reflux in patients with asthma.

A possible role of methylxanthines in the high incidence of gastroesophageal reflux (GER) in patients with asthma has been suggested. Therefore, we used a randomized, double-blind, crossover design to compare the effects of a 1-week conventional theophylline treatment and a 1-week placebo treatment in 16 adult patients with asthma. No oral or parenteral glucocorticoids were administered, but seven patients were taking inhaled corticoids. All patients needed inhaled adrenergic drugs. At the end of each period of theophylline or placebo treatment, the patients were carefully questioned with respect to respiratory and digestive symptoms, forced expiratory flows were measured, and GER was assessed by prolonged nocturnal intraesophageal pH monitoring. Peak expiratory flow was measured three times a day throughout the study. No significant increase in GER was found with theophylline compared to placebo, and forced expiratory flows improved with theophylline (p less than 0.05 for FEV1 and p less than 0.01 for peak expiratory flow rate). There was no correlation between GER, the duration of asthma, and forced expiratory flows. Thus, our study failed to demonstrate any adverse effect of a slow-release theophylline preparation on GER in patients with asthma. These results further suggest that the presence of GER is not a contraindication to the use of a slow-release theophylline in subjects with asthma.

Adrenergic beta-Agonists↗
PubMed1988

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↗
PubMed1988

Role of extracellular calcium in the effects of substance P and neurokinin A on guinea pig trachea and human bronchus.

Whether the influx of calcium through voltage-operated channels is involved in the stimulatory effects of substance P and neurokinin A in airways smooth muscle is not yet firmly established. This question was addressed in the present study using guinea pig trachea and human bronchi suspended in normal or calcium-free Krebs solution and tested with inhibitors of calcium channels. In calcium-free Krebs solution, the myotropic effects of substance P (10(-7) M), neurokinin A (3.10(-8) M), acetylcholine (2.10(-5) M), and histamine (2.10(-5) M) were reduced by 27-57%, while those of potassium chloride and tetraethylammonium were practically abolished. Calcium antagonists such as verapamil or nicardipine, when applied at concentrations of 10(-8)-10(-6) M, inhibited the contractions produced by potassium chloride and tetraethylammonium, whereas higher concentrations (10(-5)-10(-4) M) of both inhibitors were needed to reduce the effects of substance P, neurokinin A, acetylcholine, and histamine. In neither preparation did the calcium agonist Bay K 8644 (10(-6) M) modify the effects of neurokinin A, substance P, acetylcholine, or histamine, but it potentiated potassium chloride's effect on human bronchi. We conclude that transmembrane calcium influx through voltage-operated channels plays a minor role in the stimulatory effects of neurokinins in airways smooth muscle.

Animals↗
PubMed1988

Causes of error of respiratory pressure-volume curves in paralyzed subjects.

Respiratory pressure-volume (PV) curves are commonly obtained in paralyzed patients by relating airway pressure to volume changes of a syringe (Vsyr). This is based on the implicit assumption that changes in thoracic volume (Vtho) and Vsyr are equal. We undertook to verify this assumption through simultaneous measurements of Vtho by respiratory inductive plethysmography and Vsyr in six comatose, paralyzed, intubated patients. At any constant Vsyr, Vtho fell and was smaller on deflation than on inflation during inflation-deflation (ID) cycle. The rate of fall was 110 +/- 64 (SD) ml/min. During ID cycles lasting 76 +/- 7 s, thoracic PV curves showed less hysteresis and a larger compliance on deflation than PVsyr curves (12 +/- 2 vs. 18 +/- 6% and 73 +/- 13 vs. 67 +/- 12 ml/cmH2O, P less than 0.05). With PVsyr curves, hysteresis increased and compliance on deflation decreased with increasing rate of fall of Vtho. We submit that the difference between changes in Vsyr and Vtho is best explained by gas exchange and should be taken into account when performing PV curves with a syringe in paralyzed patients.

Adult↗
PubMed1988

Breathing dry air causes acute epithelial damage and inflammation of the guinea pig trachea.

Drying and cooling of the airways mucosa caused by respiratory water loss may be responsible for exercise- and hyperventilation-induced asthma. Therefore we designed this study to investigate whether breathing dry air is capable of causing structural changes of the airways mucosa. Anesthetized guinea pigs breathed spontaneously through a tracheostomy either dry (n = 15) or water-saturated (n = 12) air at approximately 38 degrees C for 30 or 60 min, during which time total pulmonary resistance (TPR) was measured. Immediately afterward, the animals were killed and the lungs and airways were prepared for histological examination (light microscopy, transmission electron microscopy, and scanning electron microscopy). With dry as well as humid air, there was no change in TPR or in the structure of the main bronchi and lung parenchyma. With humid air the tracheal mucosa was normal in six guinea pigs and exhibited minor changes of the ciliae in eight and localized epithelial damage on light microscopy in the remaining animal. With dry air we found widespread loss of the ciliae on scanning electron microscopy in 10 of 12 animals, associated with detachment or sloughing of the epithelium, subepithelial vascular congestion, edema, and cellular infiltration on light microscopy. Our data demonstrate that a short exposure of the trachea to dry air causes marked epithelial lesions and local inflammation.

Air↗
PubMed1988

Local cellular and humoral responses to antigenic and distilled water challenge in subjects with allergic rhinitis.

We studied nasal responses to allergen, saline, and distilled water aerosol in 7 subjects with allergic rhinitis to determine whether they caused a similar release of mediators and influx of inflammatory cells into the nasal lumen. The subjects were challenged first with allergen and then with aerosols of distilled water and of normal saline in random order on separate days. We measured nasal airway resistance (Rn) by posterior rhinomanometry, measured the concentrations of protein, histamine, leukotrienes (LT) B4, C4, and D4, and platelet-activating factor (PAF-acether) and performed total and differential cell counts in nasal lavage fluid obtained before and after each challenge. Allergen challenge provoked a 2-fold or greater increase in nasal airway resistance in all subjects (mean increase = 12.2-fold). This response was associated with significant increases in protein, histamine, LTB4, and sulfidopeptide leukotrienes. 2-lyso-PAF-acether increased significantly, indicating activation of phospholipase A2, but PAF-acether was detected in only one subject. The total cell count increased from 55 +/- 44 x 10(3)/ml to 200 +/- 168 x 10(3)/ml; polymorphonuclear neutrophils increased from 11 +/- 22 x 10(3)/ml to 108 +/- 96 x 10(3)/ml, and eosinophils increased from 1.3 +/- 1.8 x 10(3)/ml to 10.6 +/- 15.3 x 10(3)/ml (p less than 0.05). Saline insufflation provoked insignificant changes in mean Rn, in the levels of protein and all inflammatory mediators, and in the number and types of cells in nasal lavage fluid. Distilled water insufflation also provoked an insignificant increase in mean Rn, but there was a 14-fold increase in one subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Variability of the pulmonary vascular response to acute hypoxia in chronic bronchitis.

Hypoxic pulmonary vasoconstriction is considered as one of the factors leading to pulmonary hypertension in patients with chronic bronchitis, but the magnitude and the variability of the pulmonary vascular response to hypoxia in these patients have not been well established. We investigated the pulmonary hemodynamic changes induced by breathing two hypoxic mixtures (FIO2 = 0.15 and 0.13) in 26 patients with chronic bronchitis with airway obstruction (FEV1/VC = 49 +/- 14 percent). Results show that there is a wide variability of the pulmonary vascular response to acute hypoxia in chronic bronchitis patients, but it is not possible to say whether such differences play a role in the natural history of the disease.

Blood Pressure↗
PubMed1988

Nasal response to substance P and methacholine in subjects with and without allergic rhinitis.

We compared the rise in nasal airway resistance (NAR) provoked by topical application of substance P (SP) and of methacholine (MCH) in seventeen patients suffering from rhinitis and fourteen control subjects. Challenges with SP or MCH were separated by a week or more. NAR was measured by posterior rhinomanometry before and 10 min after intranasal administration of SP (10-40 nmol) or MCH (3-12 mumol). The two groups of subjects had similar baseline levels of NAR and similar small responses to buffered saline. Substance P but not MCH provoked cutaneous flushing in all subjects. Both SP and MCH provoked a significantly greater increase in NAR in patients suffering from rhinitis than in control subjects. The increase in NAR was dose-dependent, and on a molar basis, SP was 375-500-fold more potent than MCH. Pretreatment with 200 micrograms of a topically active anticholinergic agent, oxytropium bromide, prevented the rise in NAR caused by 12 mumol of MCH but not that caused by 40 nmol of SP in six patients suffering from rhinitis. We conclude that SP is absorbed across the nasal mucosa and causes cutaneous vasodilation, that MCH and SP cause a greater rise in NAR in patients suffering from rhinitis than in control subjects, that SP is about 500-fold more potent than MCH in increasing NAR, and that the rise in NAR caused by SP is not mediated by postganglionic parasympathetic mechanisms.

Administration, Intranasal↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

[Bronchial provocation tests using hyperventilation].

The appearance of an asthmatic crisis in the minutes following physical exercise is common in symptomatic asthma. Exercise induced asthma (EIA) is linked to hyperventilation; voluntary isocapnic hyperventilation is capable of triggering a crisis. It is well established at present that EIA and post-hyperventilation asthma (HIA) are triggered by a rise in heat and water loss by the airways, which is inherent in hyperventilation. The respective role of water loss and cooling the airways are uncertain but one tends to think at the present time that the primary stimulus is the variation in osmolality of the liquid lining the epithelium. However, a relationship between the quantity of energy dissipated in the airways and the severity of EIA or HIA exists, although it is less tight than was once thought. This is perhaps not surprising, as the intermediary mechanisms connecting the stimulus to the response of the airways are poorly understood. All in all physical exercise and isocapnic hyperventilation of dry air and possibly cold air are useful and equivalent non-specific bronchial provocation tests, if only the ventilation and physical properties of the inhaled air are the same. Hyperventilation lends itself better than exercise to establishing dose-effect curves linking bronchial response to minute ventilation. Recommendations concerning the interruption of drugs, the measurement of the response and the assessment of the results are the same as with other non specific bronchial provocation tests with irritant substances or pharmacological agents.

Asthma, Exercise-Induced↗
PubMed1986

Comparison of effects of fentanyl and alfentanil on intra-ocular pressure. A double-blind controlled trial.

The effects of fentanyl and alfentanil on intra-ocular pressure during anaesthesia were investigated in 50 consecutive patients in a double-blind controlled trial. Both drugs produced a significant reduction in intraocular pressure (p less than 0.01). Alfentanil produced significantly greater reduction (48.5 percent) than fentanyl (28.6 percent) (p less than 0.01). A small but statistically significant reduction in arterial pressure (15 percent approximately) and heart rate (18 percent approximately), were observed with both agents, but no significant differences between them were noted. It is suggested that alfentanil may be a suitable alternative to fentanyl in ophthalmic anaesthesia.

Adjuvants, Anesthesia↗
PubMed1986

A single orally administered dose of almitrine improves pulmonary gas exchange during exercise in patients with chronic air-flow obstruction.

To verify if the improvement in gas exchange observed at rest with almitrine in patients with chronic air-flow obstruction is maintained at exercise, we studied 10 patients on a randomized, crossover, double-blind exercise protocol. After assessment of steady state of their disease, patients with FEV 1 less than 1.5 L.s-1 and PaCO2 less than 70 mmHg cycled 8 to 11 min at 80% of their previously determined maximal O2 uptake. Blood gases, arterial lactate (La), expired ventilation, (VE), O2 uptake (Vo2), Co2 production (VCO2), heart rate (HR), and arterial blood pressure (BP) were measured at rest, at mid-exercise, at end-exercise, and at 2, 14, 15, and 35 min of recovery. We found that at all stages of the study PaO2 was significantly higher in those who had received almitrine than in those who had received placebo; the mean increment was 11.9 torr at rest, 8.9 at end-exercise, and 13.7 at 15 min of recovery. Changes in PaCO2 and arterial (H+) were the opposite of those in PaO2; at end-exercise PaCO2 was 5.9 torr lower in those who had received almitrine, and pH was 7.36 versus 7.32 in those who had received placebo. No significant difference was found at all stages of the study between drug and placebo with respect to VE, VO2, VCO2, HR, and BP. But the ventilatory equivalent for oxygen, VE/VO2, was slightly higher in those who had received almitrine than in those who had received placebo during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1985

Effects of nifedipine on responses to exercise in normal subjects.

The responses to sublingual nifedipine (20 mg) and placebo were compared in normal subjects during two studies on cycle ergometer [progressive exercise and constant work-load exercise at approximately 60% of maximal O2 consumption (VO2max)]. The use of nifedipine did not modify maximal power, ventilation (VE), VO2, and heart rate (HR) at the end of the multistage progressive exercise (30-W increments every 3 min). Over the 45 min of the constant-load exercise and the ensuing 30-min recovery we observed with nifedipine compared with placebo 1) no differences in VO2, VE, respiratory exchange ratio, and systolic arterial blood pressure; 2) a higher HR (P less than 0.001) and lower diastolic arterial blood pressure (P less than 0.01); 3) a greater and more prolonged rise in norepinephrine (P less than 0.01) and growth hormone (P less than 0.001); 4) no significant differences in epinephrine and insulin and a lesser increase in glucagon during recovery (P less than 0.01); and 5) a lesser fall in blood glucose (P less than 0.01) and greater increase in acetoacetate (P less than 0.001), beta-hydroxybutyrate (P less than 0.05), and blood lactate (P less than 0.001). Our data do not support the hypothesis that nifedipine reduces hormonal secretions in vivo and are best explained by an enhanced secretion of catecholamines compensating for the primary vasodilator effect of nifedipine.

3-Hydroxybutyric Acid↗
PubMed1985

[The autonomous nervous system and pulmonary circulation. Stimulation of chemoreceptors and ventilation/perfusion ratios].

The existence of neurogenic pulmonary vasomotrocity and of vasomotor reflexes elicited by stimulation of peripheral chemoreceptors has been demonstrated in different animal species. There are efferent noradrenergic and cholinergic nerve endings in the walls of musculo-pulmonary arteries. Stimulation of sympathetic efferents and exogenous noradrenaline cause vasoconstriction of pulmonary arteries when initial vasomotor tone is normal. There are also beta-adrenergic and cholinergic vasodilation pathways whose effects oppose the above mentioned vasoconstrictor ones, are blocked by the corresponding inhibitors, and can be demonstrated when initial vasomotor tone is high. The role of pulmonary vasomotor tone in the distribution of ventilation perfusion ratios is unknown. The stimulation of peripheral chemoreceptors causes a rise in pulmonary vascular resistance. Inversely, the stimulation of peripheral chemoreceptors by hypoxia prevents the local vasoconstrictor effect of localised alveolar hypoxia in sheep. There are thus theoretical reasons to think that the effect on regional pulmonary resistance of nervous stimulation may differ in cases of inhomogeneous lung disease, according to the local state of the pulmonary vessels. Consequently, it is not possible to anticipate the effect of stimulating chemoreceptors on the distribution of ventilation/perfusion ratios.

Animals↗