Biomedical subjects

M C Michoud

Publications and source records attributed to M C Michoud.

14 recordsLinked to original sources

PubMed1991

Effect of salbutamol on gastroesophageal reflux in healthy volunteers and patients with asthma.

The aim of this work was to establish whether beta-adrenergic agonists promote or increase gastroesophageal reflux in patients with asthma. Ten healthy individuals and eight patients with asthma were studied on 2 different days. One day they received a placebo, and the other day they received 4 mg of salbutamol by mouth. Complete measurements of esophageal manometry were performed before and every 30 minutes for 210 minutes after the administration of the drugs. Esophageal pH was measured continuously for the duration of the experiment. The results demonstrate that (1) salbutamol had no effect on the lower esophageal sphincter pressure gradient, the peak esophageal contraction pressure, or the number and duration of reflux episodes in patients with asthma and normal individuals, and (2) patients with asthma have a resting lower esophageal sphincter pressure higher than healthy subjects. We conclude that the administration of salbutamol does not affect esophageal function.

Adolescent↗

PubMed1989

Release of atrial natriuretic factor (ANF) induced by acute airway obstruction.

The aim of this study was to measure the effects of an increase in negative intrathoracic pressure on the release of ANF. With the subjects seated comfortably, 3 control blood samples were obtained over 30 minutes. Eight subjects then breathed for 30 min. through an inspiratory resistance in such a way that maximal inspiratory pleural pressures were between -30 to -40 cmH2O. Three blood samples were withdrawn after 20, 25, and 30 min., with the subject still breathing against the artificial resistance. Plasma concentrations of ANF were analysed by RIA. They measured: control value 24.6 +/- 3.7 pg ANF/mL (X +/- SE); with resistance 37.1 +/- 8.1 pg/mL (p less than or equal to .05). These results suggest that ANF could be released during an asthma attack.

Adult↗

PubMed1988

Sampling technique and rheology of human tracheobronchial mucus.

The aims of this work were: (1) to establish a technique for the sampling of human tracheobronchial mucus not contaminated by saliva or topical anesthesia, and (2) to measure its viscoelastic properties. After local anesthesia of the hypopharynx by topical application of 4% xylocaine, a double-sleeve microbiology specimen brush was introduced into a flexible bronchoscope placed in the trachea. The brush was left in direct contact with the bronchial mucosa for 20 to 30 s to allow mucus to collect on it. The mucus sample was then scraped from the brush and immediately covered with paraffin oil. Its viscoelastic properties were determined by the magnetic microrheometer technique. Excluding the time to anesthetize, the whole procedure took less than 1 min (thus minimizing the effect of cough) and resulted in sufficient mucus for rheologic analysis in approximately 90% of trials, i.e., 2.1 +/- 1.5 (SD) mg. Mucus specimens were collected from 20 fasting healthy nonsmoking subjects; 17 of them returned for a second collection several days later. Values for mucus mechanical impedance (vector sum of elasticity and viscosity) at 1 rad/s were: Control 1, 141 +/- 41 (SE); Control 2, 155 +/- 58 dyn/cm2. There was a large variation in mucus viscoelasticity, both between subjects (CV, 130%) and within the same subject (CV, 55%) on different days. In 7 subjects, mucus samples were collected 15 min after intravenous injection of 0.6 mg atropine. Viscoelasticity in these samples was 708 +/- 147 dyn/cm2, a value significantly different from Control 1 (p less than 0.05) and Control 2 (p less than 0.05) values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Reflex decrease of histamine-induced bronchoconstriction after laryngeal stimulation in asthmatic patients.

The aim of this work was to determine if the nonadrenergic noncholinergic nervous system can be reflexly activated in asthmatic patients by stimulating the vocal cords. The stimulation was produced by a cytology brush passed through a bronchoscope previously introduced transnasally and positioned just above the epiglottis. The subjects were premedicated with cholinergic blockers, and bronchoconstriction was induced by inhalation of histamine. In 11 experiments performed on six patients, vocal cords stimulation resulted in a decreased RL from 8.4 +/- 1.0 to 6.3 +/- 0.8 cm H2O.L-1.s (mean +/- SE) (p less than 0.01). To assess the possible contribution of circulating catecholamines to this decrease, plasma epinephrine and norepinephrine levels were measured in six experiments, before and 30 s, 1, 3, and 5 min after the stimulation. Pulmonary resistance fell from 10.0 +/- 1.3 to 7.6 +/- 0.9 cm H2O.L-1.s (mean +/- SE) (p less than 0.05) 30 s and to 7.9 +/- 0.9 cm H2O.L-1.s (p less than 0.05) 60 s after stimulation. Epinephrine and norepinephrine levels increased slightly but not significantly throughout the experiment. We conclude that in asthmatic patients, as in normal subjects, stimulation of the vocal cords produces a reflex decrease in histamine-induced bronchoconstriction which is modulated by the nonadrenergic noncholinergic nervous system.

Administration, Inhalation↗

PubMed1987

Reflex decrease of histamine-induced bronchoconstriction after laryngeal stimulation in humans.

The aim of this work was to determine whether the nonadrenergic, noncholinergic, inhibitory nervous system can be reflexly activated in humans by laryngeal stimulation. The stimulation was achieved with a cytology brush passed through a bronchoscope previously introduced transnasally and positioned just above the epiglottis. In one series of experiments, subjects were premedicated with beta-adrenergic and cholinergic blockers, and bronchoconstriction was induced by histamine inhalation. The results showed that mechanical irritation of the vocal cords with the cytology brush produced a sharp, short-lasting (less than 1 min) decrease in RL from (mean +/- SE) 6.8 +/- 2.1 to 4.8 +/- 1.5 cm H2O.L-1.s, and in the absence of parasympathetic blockade, laryngeal irritation produced a fall in RL from (mean +/- SE) 9.0 +/- 3.7 to 5.4 +/- 2.0 cm H2O.L-1.s (p less than 0.0001) (ANOVA). This decrease in RL was independent of the slight cough produced by laryngeal stimulation and reflects a change in lower and not upper airway resistance. Adequacy of the beta-adrenergic and cholinergic blockade was checked with an intravenous infusion of isoproterenol and inhaled methacholine, respectively. In 2 subjects, the fall in RL was abolished by a block of the superior laryngeal nerves and direct local anesthesia of the vocal cords. We conclude that mechanical irritation of the larynx produces a partial reversal of histamine-induced bronchoconstriction that is mediated through nervous pathways that are neither beta-adrenergic nor cholinergic in origin. We suggest that this decrease in bronchoconstriction is modulated by the nonadrenergic, noncholinergic, inhibitory nervous system.

Adult↗

PubMed1986

Prolonged hyporesponsiveness of airway smooth muscle to histamine following general anesthesia.

The prolonged effect of barbiturates and inhalation anesthesia on airway response to histamine was studied in five groups of dogs. Group B (n = 10), H24 (n = 5), and H72 (n = 5) were anesthetized with sodium thiamylal (B) or halothane and N2O (H24, H72) for 3 h, during which a dose-response curve to histamine was obtained. The animals were then allowed to recover; 24 h (B and H24) or 72 h later, the animals were killed and an in vitro dose-response curve to histamine was obtained on a tracheal smooth muscle (TSM) specimen. Group C (n = 5), the control group, had no prolonged exposure to anesthesia. The dogs were immediately killed and the in vitro histamine response of the TSM was measured. The results (mean +/- SE) showed that the smooth muscle contractile properties (i.e., the maximum contraction to electrical field stimulation) were comparable in all four groups: 111 +/- 12 g (B); 168 +/- 23 g (H24); 106 +/- 32 g (H72); and 107 +/- 31 g (C). The maximum response (mean +/- SE) to histamine (as % of maximum electrical contraction) was: 15 +/- 6% (B), 30 +/- 9% (H24), 32 +/- 12% (H72), and 50 +/- 8% (C). Statistical analysis of the data showed that the histamine response of Group B and Group H24 was significantly decreased compared to Group C (P less than 0.01 and less than 0.05, respectively); in Group H72 the results were not significantly different from Group C (0.1 greater than P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

PubMed1979

The pathophysiology of asthma.

Because postmortem studies of humans provide little information on the initial pathophysiologic events in asthma, animal models have been developed. Recently the Ascaris-allergic rhesus monkey has provided an opportunity to examine the onset of pathophysiologic changes following challenge and to correlate them with airway structure. These studies have suggested that the initial interaction between antigen and mast cells may occur in the bronchial lumen or in the epithelium superficial to the tight junctions, where a small but significant percentage of airway mast cells exist. It also appears that this initial antigen-antibody interaction results in the release of mediators that both stimulate the rapidly adapting stretch receptors in the mucosa and alter the mucosal barrier so that proteins of large molecular weight can penetrate. The fact that antigen challenge results in hyperresponsiveness to a subsequent dose of inhaled histamine and increased systemic absorption of histamine suggests that the airway hyperresponsiveness could be related to increased penetration of histamine into the bronchial wall. These observations suggest that the initial event in an acute asthmatic attack is the release of mediators from superficial mast cells, and that this amplifies the allergic response by altering the mucosal permeability so that more antigen reaches the submucosal mast cells. This altered permeability may also help explain the hyperreactivity of the airways to nonspecific airway stimulants in persons with asthma.

Airway Resistance↗

PubMed1979

Pulmonary effects of acute and chronic antigen exposure of immunized guinea pigs.

Subdivisions of lung volume and pressure-volume (PV) curves of the lung and chest wall were measured in guinea pigs immunized to ovalbumin before and after acute (group 1) and chronic (group 2) antigen exposure. The histopathology produced in chronically exposed animals was also assessed. Animals were anesthetized with pentobarbital sodium and studied in a pressure-sensitive body plethysmograph, using a fluid-filled esophageal catheter to measure transpulmonary pressure (PL). Functional residual capacity (FRC) was determined by the Boyle's law technique; total lung capacity (TLC) was defined as the lung volume at a PL of 30 cmH20, and residual volume (RV) was defined as the lung volume at a transrespiratory pressure of -50 cmH2O. Acute antigen challenge of group 1 animals resulted in a decrease in TLC (22%), and increases in FRC (20%) and RV (110%), suggesting combined bronchoconstriction and alveolar duct constriction. Chronic antigen exposure of group 2 animals resulted in minimal changes in subdivisions of lung volume and PV curves, and produced a histological lesion resembling allergic alveolitis rather than asthma.

Aerosols↗

PubMed1979

The number and distribution of mast cells in monkey lungs.

We estimated the number of mast cells in monkey lungs by both quantitative histologic examination and measurement of total lung histamine, and showed that monkey lungs contain between 10(7) and 10(8) mast cells, with approximately 83% of these being located in conducting airways, and 17% in the parenchyma. The number of mast cells found in each airway generation increased from approximately 60,000 in the trachea to 8 million in the terminal bronchioles. In airways from different generations the number of mast cells superficial to the basement membrane in the epithelium and lumen (EMC) was compared to the number of mast cells found in the submucosa between basement membrane and cartilage and to the number of those found outside the cartilage. The number of EMC varied between animals and ranged from 0-0.4% of the total number of mast cells in the trachea, to 0-27% of the total in the terminal bronchioles. On the average, EMC accounted for 12% of the total number of mast cells in conducting airways, where we calculate that there is approximately one EMC for every 100,000 epithelial cells. Eosinophils were distributed in close relation to mast cells in the mucosa and submucosa, but were rare outside the cartilage. We conclude that the number of mast cells increases from central to peripheral airways and that this may account for the marked peripheral airway response observed after antigen challenge.

Animals↗

PubMed1979

Airway sensitivity to slow-reacting substance of anaphylaxis, histamine, and antigen in Ascaris sensitive monkeys.

The effects of Ascaris suum antigen, histamine, and slow-reacting substance of anaphylaxis (SRS-A) on the respiratory system were compared in 3 anesthetized rhesus monkeys. The agents were administered by instillation into the trachea, and the animals were studied in a volume displacement body plethysmograph. Two of the animals showed skin and bronchial sensitivity to Ascaris suum antigen and responded to it with increased pulmonary resistance and decreased dynamic compliance. A similar response was seen in all 3 animals after instillation of histamine, but SRS-A at 2 concentrations produced a predominant effect of decreased dynamic compliance with lesser alterations in pulmonary resistance. The effects of SRS-A were slow in onset and prolonged, as compared to the abrupt and short-lived effects of Ascaris suum antigen and histamine. The predominant effect of SRS-A on dynamic compliance suggests a more peripheral site of action of this mediator. In 5 monkeys allergic to Ascaris, no SRS-A could be detected in the blood at one and 5 min after antigen challenge, using the bioassay techniques.

Administration, Topical↗

PubMed1978

Static lung mechanics of intact and excised rhesus monkey lungs and lobes.

Subdivisions of lung volume and pressure-volume (PV) curves of the lung and chest wall (CW) were measured in 12 rhesus monkeys (Macacca mulatta) under pentobarbital anesthesia. In addition, volumes and PV curves were obtained on the excised lungs and lobes of 12 cynomolgus monkeys (M. fasicularis). Boyle's law was used to determine functional residual capacity (FRC) in the intact animals and water displacement to determine minimal volume (MV) in the excised lungs. Total lung capacity (TLC = lung volume at a transpulmonary pressure of 30 cmH2O) was similar in vivo and in vitro (90 + 83 ml/kg) but residual volume (RV = volume at airway pressure of -50 cmH2O) and MV differed markedly (16.5 + 5.9 ml/kg). In the intact animals a very stiff CW appeared to determine RV, whereas airway closure determined MV in excised lungs. PV curves of upper and lower lobes were not different when expressed as %TLC but when expressed as milliliters of gas per gram of lung, the upper lobes contained significantly more gas per unit weight.

Animals↗

PubMed1978

Airway responses to histamine and methocholine in Ascaris suum-allergic rhesus monkeys.

We performed dose-response curves to inhaled histamine (H) and methacholine (MC) in a group of eight rhesus monkeys, with and without natural allergy to Ascaris suum antigen (AA). The animals were anesthetized with pentobarbital sodium, 25 mg/kg im and studied in a volume-displacement body plethysmograph. The dose of H or MC producing a 50% increase in pulmonary resistance (RL) was used to determine sensitivity to these agents and the increase in RL at a given dose was employed as a measure of reactivity. Sensitivity and reactivity to H and MC were then compared with AA responsiveness. A wide range of responses was observed but allergic animals were not more sensitive or reactive to H or MC than nonallergic animals. In addition, we studied the changes in breathing pattern that occurred during the inhalation of AA, H, and MC in four AA-sensitive animals. AA and H produced rapid shallow breathing within 30 s of starting inhalation, but MC, despite causing an equal degree of bronchoconstriction, did not produce alterations in breathing pattern.

Aerosols↗

PubMed1976

Effect of indomethacin and atropine in experimental asthma in conscious guinea pigs.

Pulmonary mechanics were measured in unanesthetized guinea pigs sensitized to horseradish peroxidase (HRP) before and during two aerosolized challenges of this antigen. During the first challenge the pulmonary resistance increased in all animals. Prior to second challenge the animals received either atropine (0.2 mg/kg) or indomethacin (10 mg/kg) intraperitoneally. We found that during the second challenge the indomethacin group had an increase in pulmonary resistance slightly greater or similar to that during the first exposure to the antigen, while the animals treated with atropine had a significantly diminished response (P less than 0.05). In five guinea pigs sensitized to HRP but challenged with a nonspecific aerosal made up of rabbit albumin, we found that pulmonary resistance increased in some animals and that this increase could be partially blocked by atropine. These results show that indomethacin has no effect on this model of allergic airways disease. They also confirm the importance of the vagus nerves in allergic bronchoconstriction and in addition show that nonspecific hyperirritability can be induced in some animals by immunization.

Aerosols↗

PubMedDate not supplied

The effect of dopamine on tracheal smooth muscle.

Dose-response curves to dopamine were obtained on guinea-pig, dog and human tracheal smooth muscle. Dopamine produced a relaxation of the guinea-pig tracheal chain, and this relaxation was completely blocked by propranolol. The potency of dopamine as a beta-agonist was 1/10 000 that of isoprenaline, 1/250 that of adrenaline and 1/50 that of noradrenaline. In human and dog tracheal smooth muscle, dopamine induced a contraction which could be entirely abolished by alpha-adrenoceptor antagonists. As an alpha-agonist, the potency of dopamine was 1/20 that of adrenaline and noradrenaline. Our data also show that a dopamine induced contraction is greatly potentiated if the smooth muscle specimen has been previously slightly contracted with histamine. We conclude that there are few, if any, specific dopaminergic receptors in the airways. Dopamine acts on both alpha- and beta-adrenoceptors, but in humans and dogs, its effect is predominantly on alpha-adrenoceptors.

Animals↗