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Biomedical subjects

M C Michoud

Publications and source records attributed to M C Michoud.

At least 19 recordsLinked to original sources
PubMed2003

Effects of hypoxia on rat airway smooth muscle cell proliferation.

Although it is well known that hypoxemia induces pulmonary vasoconstriction and vascular remodeling, due to the proliferation of both vascular smooth muscle cells and fibroblasts, the effects of hypoxemia on airway smooth muscle cells are not well characterized. The present study was designed to assess the in vitro effects of hypoxia (1 or 3% O(2)) on rat airway smooth muscle cell growth and response to mitogens (PDGF and 5-HT). Cell growth was assessed by cell counting and cell cycle analysis. Compared with normoxia (21% O(2)), there was a 42.2% increase in the rate of proliferation of cells exposed to 3% O(2) (72 h, P = 0.006), as well as an enhanced response to PDGF (13.9% increase; P = 0.023) and to 5-HT (17.2% increase; P = 0.039). Exposure to 1% O(2) (72 h) decreased cell proliferation by 21.0% (P = 0.017) and reduced the increase in cell proliferation induced by PGDF and 5-HT by 16.2 and 15.7%, respectively (P = 0.019 and P = 0.011). A significant inhibition in hypoxia-induced cell proliferation was observed after the administration of bisindolylmaleimide GF-109203X (a specific PKC inhibitor) or downregulation of PKC with PMA. Pretreatment with GF-109203X decreased proliferation by 21.5% (P = 0.004) and PMA by 31.5% (P = 0.005). These results show that hypoxia induces airway smooth muscle cell proliferation, which is at least partially dependent on PKC activation. They suggest that hypoxia could contribute to airway remodeling in patients suffering from chronic, severe respiratory diseases.

Animals↗
PubMed1999

Mechanisms of the potentiation by adenosine of adenosine triphosphate-induced calcium release in tracheal smooth-muscle cells.

The effects of concomitant P1-receptor stimulation on peak intracellular Ca2+ release by extracellular adenosine 5'-triphosphate (ATP) and 5-hydroxytryptamine (5-HT) were investigated in cultured airway smooth-muscle (ASM) cells. The results show that peak Ca2+ release to ATP is enhanced by preincubation with adenosine (ADO) and with the specific A3 receptor agonist 1-Deoxy-1-(6-([(3-iodophenyl)methyl] amino)-9H-purin-9-yl)-N-methyl-beta-D-ribofuranuronamide (1B-MECA). The response to 5-HT, a smooth-muscle contractile agonist, was also enhanced after preincubation with ADO. Further measurements showed that this enhancement of the response to ATP was dependent on extracellular calcium because it was abolished by the removal of Ca2+ from the extracellular fluid and by incubation with the calcium channel blocker nifedipine. In addition, there was no difference between the levels of total inositol phosphates measured in the presence of ATP alone or of ADO + ATP. AACOCF3, a specific blocker of phospholipase A2, decreased the peak Ca2+ response to ATP and abolished the enhanced response to ATP and 5-HT produced by ADO. We conclude that stimulation of P1 and P2 receptors in ASM cells activates not only phospholipase C but also phospholipase A2. The enhancement of ATP-induced and 5-HT-induced Ca2+ release is due to Ca2+ influx from the extracellular fluid through a Ca2+ channel presumably modulated by arachidonic acid. These data show that endogenous ADO may modulate airway hyperresponsiveness by enhancing the ASM response to contractile agonists.

Adenosine↗
PubMed1997

Effects of purine nucleotides and nucleoside on cytosolic calcium levels in rat tracheal smooth muscle cells.

Extracellular adenosine triphosphate (ATP) has a range of effects on a wide variety of cells through the activation of specific purinoceptors. The aim of this study was to establish whether P2 purinoceptors are present on airway smooth muscle cells. Experiments were conducted on cultured rat tracheal smooth-muscle cells (first through third passage). Intracellular Ca2+ ([Ca2+]i) was measured using Fura-2 and dual-excitation wavelength microfluorometry. The effects of ATP, adenosine diphosphate (ADP), uridine triphosphate (UTP), and adenosine (ADO) were measured in concentrations from 10(-6) to 10(-3) M. At a concentration of 10(-4) M, the peak [Ca2+]i was 502 +/- 92 nM for ATP and 543 +/- 76 nM for UTP (mean +/- standard error of the mean). ADO had no significant effect on Ca2+ release. Peak [Ca2+]i induced by ATP was not dependent on extracellular Ca2+ but was blocked by U-73122, an inhibitor of phospholipase C. Pretreatment with adenosine deaminase and desensitization with alphabeta-MeATP had no effect on ATP-induced Ca2+ release. The effects of ATP (10(-4) M) on peak [Ca2+]i were potentiated by the presence of ADO 10(-5) M (969 +/- 257 nM; P < 0.05). The presence of XAC, a blocker of A1 and A2 ADO receptors did not prevent this effect. In the presence of XAC, ADO 10(-6) M potentiated the effects of ATP (peak [Ca2+]i: 1,300 +/- 229 nM). The addition of 1433U83, a blocker of A3 ADO receptors, blocked the synergistic effect of ADO 10(-6) M on ATP. These data show that P2 purinoceptors, most likely of the P2U subtype, are present on airway smooth muscle cells and that the newly discovered A3 ADO receptor appears to be also present.

Animals↗
PubMed1995

Maternal asthma and idiopathic preterm labor.

Previous studies suggest that women with asthma are at increased risk of preterm birth. Moreover, drugs (especially beta-agonists) used to treat asthma are also used to treat preterm labor. The authors carried out a case-control study of 555 women from three hospital centers with idiopathic preterm labor (< 37 weeks), including two overlapping (i.e., non-mutually exclusive) subsamples: cases with early idiopathic preterm labor (< 34 weeks) and cases with idiopathic recurrent preterm labor (< 37 weeks plus a previous history of preterm delivery or second-trimester miscarriage). Controls were matched to cases according to race and smoking history prior to and during pregnancy. All subjects responded in person to questions about atopic, respiratory, obstetric, and sociodemographic histories. Subjects in the early and recurrent preterm labor subsamples were also asked to undergo spirometric testing with methacholine challenge 6-12 weeks after delivery. Cases were significantly more likely to report histories of asthma symptoms and physician-diagnosed asthma (matched odds ratios of 2-3) than controls, particularly those cases with recurrent preterm labor. No significant associations were observed, however, with methacholine responsiveness. These results could not be explained by residual confounding by smoking or other variables, nor by selective recall of asthma symptoms and histories by cases. Women with asthma are at increased risk of idiopathic preterm labor. The fact that no such association was seen with methacholine responsiveness suggests that nonatopic, noncholinergic mechanisms may link bronchial and uterine smooth muscle lability.

Adult↗
PubMed1995

Maternal anthropometry and idiopathic preterm labor.

OBJECTIVE: To assess the etiologic role of maternal short stature, low pre-pregnancy body mass index (BMI), and low rate of gestational weight gain in idiopathic preterm labor. METHODS: We carried out a three-center case-control study of 555 women with idiopathic onset of preterm labor (before 37 completed weeks), including two overlapping (ie, nonmutually exclusive) subsamples: cases with early preterm labor (before 34 completed weeks) and cases with recurrent preterm labor (before 37 completed weeks plus a history of prior preterm delivery or second-trimester miscarriage). Controls were matched to cases by race and smoking history. All subjects responded in person to questions about height, pre-pregnancy weight, gestational weight gain, and obstetric and sociodemographic histories. RESULTS: Maternal height, pre-pregnancy weight, and gestational weight gain demonstrated excellent test-retest reliability, with intra-class correlation coefficients of 0.97, 0.99, and 0.91, respectively. Based on matched analyses, women with a height of 157.5 cm or less had an increased risk of idiopathic preterm labor (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.25-2.74), as did those with a pre-pregnancy BMI less than 19.8 kg/m2 (OR 1.63, 95% CI 1.09-2.44) or a gestational weight gain rate less than 0.27 kg/week (OR 1.74, 95% CI 1.16-2.62). Conditional logistic regression models containing all three anthropometric variables and controlling for parity, marital status, language, age, and education yielded virtually identical point estimates and CIs. CONCLUSION: Maternal short stature, low pre-pregnancy BMI, and low rate of gestational weight gain may lead to shortened gestation by increasing the risk of idiopathic preterm labor.

Anthropometry↗
PubMed1995

Plasma atrial natriuretic peptide during spontaneous bronchoconstriction in asthmatics.

The aim of this work was to establish the role of endogeneous ANP during a spontaneous asthma attack. Forced expiratory lung volume in 1 s (FEV1), cardiovascular parameters, and plasma ANP, cAMP, and cGMP were measured for 60 min before and 10 min after treatment with a bronchodilator in 10 asthmatics. The results show that in the presence of moderate bronchoconstriction, FEV1 was 54 +/- 3% (+/-SE); ANP levels initially were slightly elevated at 47 +/- 10 pg/ml and decreased to 26 +/- 3 pg/ml (p < 0.05) over 60 min, with no change in FEV1. Following salbutamol inhalation, FEV1 increased to 77 +/- 4% with no change in ANP. We conclude that endogenous ANP does not act as a bronchodilator in asthmatics with moderate bronchospasm.

Acute Disease↗
PubMed1995

Plasma concentrations and effects of salbutamol administered orally to patients with cystic fibrosis.

1. To test whether cystic fibrosis (CF) altered the kinetics and dynamics of oral salbutamol, 11 patients with CF (19-33 years old; five females; FEV1: 37 +/- 12% of predicted value) and 10 healthy volunteers (20-41 years old; five females; FEV1: 99 +/- 14% of predicted value) received orally 4 mg salbutamol. 2. The estimated pharmacokinetic parameters of salbutamol in patients with CF were identical to those in healthy subjects. For instance, peak plasma concentrations of salbutamol were 10.5 +/- 2.6 (mean +/- s.d.) and 10.2 +/- 2.9 ng ml-1 (NS), and the area under salbutamol plasma concentrations as a function of time (AUC (0, 7 h)) was 43.0 +/- 9.3 ng ml-1 h and 43.3 +/- 12.7 ng ml-1 h (NS) in CF patients and in healthy subjects, respectively. Since on a mg kg-1 dose basis, CF patients received a dose 28% greater than healthy subjects, this lack of differences implies a decrease in the amount of salbutamol absorbed, or alternatively, an increase in both clearance and volume of distribution of salbutamol. 3. Salbutamol did not elicit bronchodilation in CF patients, but increased heart rate from 77 +/- 2 to 103 +/- 3 beats min-1 (P < 0.05). 4. Salbutamol decreased plasma potassium concentrations from 4.5 +/- 0.1 to 3.8 +/- 0.1 mmol l-1 in the CF group (P < 0.05) and from 4.1 +/- 0.2 to 3.4 +/- 0.1 mmol l-1 in the controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Effect of intravenous atrial natriuretic peptide on gas exchange in humans.

The aim of this work was to establish whether a physiological increase in atrial natriuretic peptide (ANP) plasma levels affects pulmonary gas exchange in humans. Ten volunteers received an infusion of either ANP (4 pmol.kg-1.min-1) or physiological saline, for 60 min. Baseline measures of the alveolar-arterial PO2 difference and of the physiological dead space were within normal limits and remained stable during and after the infusion of ANP or saline, although plasma ANP and cGMP rose significantly (p < 0.01) (mean +/- SEM: ANP: 13.4 +/- 3.9 to 56.0 +/- 10.4 pmol/l; cyclic GMP: 3.8 +/- 0.3 to 17.0 +/- 3.8 nmol/l). We conclude that a physiological increase in plasma ANP does not affect pulmonary gas exchange significantly in humans.

Adult↗
PubMed1994

[Bronchial hyperreactivity: neurogenic factors].

Over the last fifty years, the role of neurogenic factors in asthma and bronchial hyperreactivity has been intensively investigated. The roles of the cholinergic and adrenergic nervous systems have been clarified and several sub-types of muscarinic receptors identified. The localisation and functions of both muscarinic and adrenergic receptors have been further specified. It has also been shown that afferent nerve fibers as well as sympathetic and parasympathetic nerve fibers secrete various neuropeptides. The physiological role of these peptides is not yet known but it appears that they have a powerful effect on bronchial smooth muscle tone, microvascular permeability, mucus secretion and secretion of mediators by inflammatory cells. The results of numerous studies suggest that there are several abnormalities in the adrenergic and cholinergic nervous systems of asthmatic patients, but that these abnormalities are not themselves the cause of bronchial hyperreactivity. They may however contribute to enhance it. The role of the various newly identified neuropeptides in the genesis and maintenance of bronchial hyperreactivity remains to be determined.

Adrenergic Fibers↗
PubMed1993

Muscarinic effect of atrial natriuretic peptide on rabbit airways.

1. The aim of the present work was to investigate under which circumstances atrial natriuretic peptide (ANP) modulates airway resistance. 2. Of the six groups of rabbits (n = 5) studied, three received an infusion of ANP (80 ng min-1 kg-1 i.v.) for a period of 100 min, while the other three were infused with the vehicle. Before receiving the infusion of ANP or the vehicle, the animals were pretreated with atropine (0.5 mg kg-1 i.v.), propranolol (2 mg kg-1 i.v.) or not pretreated. After 75 min of infusion of ANP, bronchoconstriction was induced by inhalation of histamine. Respiratory resistance (Rrs) was measured before and 3, 5, 10, 15 and 20 min post-histamine challenge. 3. Following 75 min of ANP infusion, plasma ANP concentration increased from 153 +/- 52 (mean +/- s.e.mean) to 1441 +/- 203 pg ml-1 (P < 0.05) without affecting baseline Rrs. Control Rrs values (12.5-20.4 cmH2O l-1 s) were significantly increased following the inhalation of histamine (P < 0.001). By themselves, atropine, propranolol or ANP did not modify the histamine-induced increase in Rrs. However, when the animals were pretreated with atropine, ANP infusion significantly reduced the increase in Rrs induced by histamine (30 +/- 2 vs 51 +/- 6 cmH2O l-1 s; P < 0.05). 4. These data suggest that ANP has an indirect modulating effect on the airway smooth muscle and will decrease Rrs when muscarinic receptors are blocked.

Airway Resistance↗
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↗
PubMed1984

Dopamine effect on bronchomotor tone in vivo.

The effect of increasing doses of dopamine (inhaled or infused) on pulmonary resistance (RL) was measured in 4 normal and in 4 asthmatic subjects. Dopamine, in doses sufficient to raise systolic blood pressure 25 mmHg, did not change RL. However, dopamine, inhaled and infused, significantly decreased histamine-induced bronchoconstriction both in normal and in asthmatic subjects. Thus, we conclude that if dopamine is released by the adrenal medulla during an asthmatic attack, it should have a beneficial rather than a deleterious effect.

Adult↗