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Biomedical subjects

M Aubier

Publications and source records attributed to M Aubier.

At least 19 recordsLinked to original sources
PubMed1992

[Drugs for asthmatic crisis].

The drugs used in asthmatic attacks must act on the two major mechanisms of the disease: bronchial obstruction and inflammation of the airways. Two main classes of drugs are available to reach these targets: bronchodilators, headed by beta 2-stimulants, and anti-inflammatory drugs of the corticosteroid family. Bronchodilatation obtained with beta 2-stimulants is the first and most effective treatment of the attack. These drugs are usually administered by inhalation: metered-dose aerosols with or without inhalation chambers, or nebulization for severe attacks. Very high doses can be used without fear of side-effects, the principal objective of this treatment being to relieve bronchial obstruction. In the absence of rapid and lasting improvement bronchodilators must always be combined with corticosteroids. In all cases medical supervision immediately after the attacks is necessary and the patient should subsequently be put under care of pneumologists.

Anti-Inflammatory Agents↗
PubMed1992

Does a subparalysing dose of vecuronium enhance diaphragm fatigue?

We have examined, in six healthy volunteers, the effect of a subparalysing dose of vecuronium on the development of diaphragm fatigue. Vecuronium was given as a 0.5-mg bolus i.v. followed by 0.5 mg infused over 30 min; as a control, saline was given in random order. Diaphragm strength was assessed by measuring transdiaphragm pressure and by electromyography. Diaphragm fatigue was induced by breathing against an inspiratory resistance. The plasma concentration of vecuronium varied between 15 and 30 ng ml-1 15 min after administration of vecuronium was started. Peripheral neuromuscular block was not detected in any subject. Diaphragm fatigue developed within the same period in both groups: mean 334 (SD 166) s after saline and 345 (190) s after vecuronium. The electromyographic pattern of diaphragm fatigue and the time constant of relaxation of transdiaphragm pressure after fatigue were similar in both groups. We conclude that, at low plasma concentrations of vecuronium, similar to those present in the postoperative period, there was no predisposition to diaphragm fatigue.

Adult↗
PubMed1992

Penetration of cefpodoxime proxetil in lung parenchyma and epithelial lining fluid of noninfected patients.

The pulmonary disposition of cefpodoxime was studied in 12 patients with pulmonary opacities after a single oral dose of 260 mg of cefpodoxime-proxetil, which is equivalent to 200 mg of cefpodoxime. Blood and lung tissue samples were collected during surgery, and bronchoalveolar lavage was carried out 3 h (group A) or 6 h (group B) after drug administration. Urea was used as an endogenous marker for measurement of the volume of epithelial lining fluid (ELF). Concentrations were measured by using a microbiological assay. The mean concentrations of cefpodoxime in plasma, ELF, and lung tissue were, respectively, 1.85 +/- 0.82 mg/liter, 0.22 +/- 0.13 mg/liter, and 0.89 +/- 0.80 mg/kg of body weight in group A and 1.40 +/- 1.25 mg/liter, 0.12 +/- 0.14 mg/liter, and 0.84 +/- 0.61 mg/kg in group B. Concentrations in lung parenchyma 6 h after dosing were at least equal to or above the MICs for 90% of the strains of most organisms commonly found in respiratory tract infections, whereas data for ELF suggest levels of drug insufficient to inhibit bacteria.

Administration, Oral↗
PubMed1992

Effects of endotoxic shock on diaphragmatic function in mechanically ventilated rats.

Diaphragmatic function was investigated in mechanically ventilated rats during endotoxic shock (group E, n = 18) and after saline solution injection (group C, n = 8). Endotoxic shock was produced by a 1-min injection of Escherichia coli endotoxin (10 mg/kg iv) suspended in saline. Diaphragmatic strength was assessed before (T0) and 15 (T15) and 60 (T60) min after injection by measuring transdiaphragmatic pressure (Pdi) generated during bilateral phrenic stimulation at 0.5, 10, 20, 30, 50, and 100 Hz. Diaphragmatic neuromuscular transmission was assessed by measuring the integrated electrical activity of the diaphragm. Diaphragmatic endurance was assessed 75 min after injection from the rate of Pdi decline after a 30-s continuous 10-Hz phrenic stimulation. In 16 additional animals, diaphragmatic glycogen content was determined 60 min after inoculation with endotoxin (n = 8) or 0.9% sodium chloride solution (n = 8). Diaphragmatic resting membrane potential (Em) was measured in 16 additional animals 60 min after endotoxin (n = 8) or saline injection (n = 8). Mean blood pressure decreased from 74 +/- 3 to 53 +/- 6 mmHg at T60 in group E, whereas it was maintained in group C. At T60 Pdi was decreased in group E for frequencies of 50 and 100 Hz and was associated with a decreased diaphragmatic electromyographic activity of 25.3 +/- 2.5 and 26.5 +/- 5.2% for 50- and 100-Hz stimulations, respectively, in comparison with T0 values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

In vivo effects of Escherichia coli endotoxemia on diaphragmatic microcirculation in rats.

We investigated the effects of Escherichia coli endotoxin administration on diaphragmatic microcirculation in rats by in vivo videomicroscopy. Rats were allocated into three groups: 1) intravenous inoculation of 10 mg/kg of E. col endotoxin (group E, n = 25), 2) intravenous inoculation of sterile 0.9% NaCl (group C, n = 20), and 3) induction of a controlled hemorrhage by reducing the vascular volume via an arterial catheter (group H, n = 15). Mean blood pressure (BP) and arteriolar diameters were measured at 15-min intervals and capillary perfusion pattern at 30-min intervals for 1 h. BP decreased similarly in groups E and H, whereas it was maintained in group C. Arterioles were classified as second (A2, n = 46), third (A3, n = 22), and fourth (A4, n = 21) order, according to their relative localization in the network. Basal diameters were the same in the three groups: 38.16, 17.33, and 6.80 microns in group C; 38.17, 17.41, and 7.04 microns in group E; and 37.82, 19.19, and 6.99 microns in group H for A2, A3, and A4, respectively. During the observation period, a significant and similar vasoconstriction of A2 arterioles was observed in groups E and H but not in group C. By contrast, in the three groups, no significant changes in diameter were found for the A3 and A4 arterioles. Capillary perfusion was markedly impaired in group E: at 60 min the percentage of non-perfused capillaries was 40.92 +/- 6.65% in group E compared with 21.17 +/- 5.45% in group C (P less than 0.05) and 18.18 +/- 8.11% in group H (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Diaphragmatic microcirculation during halothane and isoflurane exposure in pentobarbital-anesthetized rats.

We investigated the effects of halothane and isoflurane on diaphragmatic microcirculation in pentobarbital-anesthetized rats by in vivo video microscopy. After a baseline period, rats were randomly allocated into three groups according to administration of 0.5, 0.75, and 1 minimal alveolar concentration (MAC) of either halothane (group Hal, n = 16), isoflurane (group Iso, n = 14), or no halogenated agent (group C, n = 20) in three succeeding steps of 15 min. Mean arterial blood pressure (MAP), arteriolar diameters, and functional capillary density were analyzed in the last 3 min of each step. MAP remained unchanged in group C but decreased in a dose-dependent manner in both halogenated receiving groups. MAP was significantly lower in rats breathing Hal compared with those breathing Iso. Arterioles were classified in second (A2, n = 39), third (A3, n = 24), and fourth (A4, n = 30) order according to their relative location in the network. No changes in A2 and A3 diameters were noted in either group. A4 diameters remained unchanged in groups C and Iso, whereas a significant reduction was found in group Hal at 0.75 and 1 MAC exposure (P < 0.05 compared with baseline and with groups C and Iso, respectively). During Iso exposure, functional capillary density was not significantly different when compared with baseline and group C, whereas in group Hal it decreased significantly at 0.5, 0.75, and 1 MAC, amounting to 61.1 +/- 9, 30.7 +/- 10.3, and 22.8 +/- 6.3%, respectively, of baseline (P < 0.01 vs. baseline and P < 0.05 vs. groups Iso and C for 0.75 and 1 MAC).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1992

Different effects of nasal and bronchial glucocorticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis.

Disorders of the upper respiratory tract, particularly allergic rhinitis, are commonly associated with bronchial hyperresponsiveness. The latter may be due to postnasal drip or to mediator or chemotactic factors into the lower airways that either directly alter airway reactivity or cause airway inflammation. The aim of this study was to compare the effect of an identical dose of nasal or bronchial corticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis. Eleven patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves, and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol that decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. Control measurements were repeated at 1-wk intervals to ensure that PD35 was stable in all the patients. Then the patients received for 2 wk, in a double-blind randomized crossover fashion, a topical administration of either an aerosol of 400 micrograms of beclamethasone dipropionate (B) into the nose (100 micrograms four times per day) or into the bronchi. During each trial period, identical sprays of placebo were used, the latter being administered into the nose when B was administered into the bronchi and vice versa. Measurements were then performed after 2 wk of intranasal administration and after 2 wk of intrabronchial administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Effect of steroids on diaphragm of newborn, weanling adolescent, and adult rats.

The purpose of this study was to compare the effects of dexamethasone on the rat diaphragm during the postnatal period and into adulthood. Groups of 48 newborn, 60 weanling adolescent, and 60 adult rats were either (1) treated with DXM (ST, steroid-treated animals) or (2) untreated and pair-fed (C, control animals). After birth, 24 newborn rats were kept with their mother, which received a daily intramuscular injection of 0.5 mg/kg body weight of dexamethasone for 2 wk. Groups of thirty weanling adolescent and 30 adult rats were treated with 1 mg/kg/day of dexamethasone given intramuscularly for 2 wk. Diaphragm performance was compared between ST animals and age-matched C animals. Weights of the body, the diaphragm, the extensor digitorum longus (EDL), and the soleus were obtained. Diaphragm strips were studied in an in vitro preparation to assess contractile and endurance properties. In all the ST animals, body and total diaphragm weights were reduced compared with age-matched C animals (p less than 0.001). In newborn and weanling adolescent ST animals, loss in diaphragm weight was slightly less than in limb muscles, in contrast to adult animals (p less than 0.05). However, diaphragms from adult and weanling adolescent ST animals showed unaffected twitch characteristics, normalized force-frequency curves, and endurance capacity. In the meantime, in newborn ST animals, diaphragm atrophy was associated with significantly decreased force normalized for fiber cross-sectional area and muscle weight (p less than 0.01) and decreased endurance capacity (p less than 0.05). We conclude that the effects of DXM on the diaphragm depend on the developmental status of the muscle at the time of drug administration.

Age Factors↗
PubMed1992

Effects of N-acetylcysteine on diaphragmatic function and malondialdehyde content in Escherichia coli endotoxemic rats.

We evaluated the effects of sublethal Escherichia coli endotoxemia with or without concomitant administration of N-acetylcysteine, an antioxidant agent, on diaphragmatic strength, endurance, and malondialdehyde (MDA) content in rats. One hundred ninety rats were inoculated subcutaneously on 2 successive days with 0.6 and 1.2 mg/100 g body weight of E. coli lipopolysaccharide respectively (E animals, n = 100) or saline (C group, n = 90). E and C animals were divided into two groups based on administration of endotoxin or saline alone (E group, n = 55; C group, n = 47, respectively) or endotoxin or saline plus N-acetylcysteine (1 g/kg body weight/day intraperitoneally) (E-NAC group, n = 45; C-NAC group, n = 43, respectively). Diaphragmatic strength was assessed in vivo 48 h after the first endotoxin or saline administration by measuring the transdiaphragmatic pressure (Pdl) generated during electrical stimulation of the phrenic nerves at 0.5, 10, 20, 30, 50, and 100 Hz. Endurance index was calculated as the percent ratio of Pdl generated after 30 s of phrenic stimulation at 10 Hz divided by the initial force. Diaphragmatic MDA (fluorometric technique) was measured 0, 6, 18, 30, 42, and 48 h after the first dose of endotoxin or saline. Pdl for 50 and 100 Hz was significantly reduced in Group E as compared with group C. This phenomenon was associated with a reduced endurance performance as assessed by a lower diaphragmatic endurance index in E as compared with C animals (90.9 +/- 4.2 versus 114.3 +/- 4.1 respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1992

In vitro functions of the rat diaphragm during postnatal development.

This study was designed to determine the developmental changes in the functional characteristics of the rat diaphragm. A total of 150 animals were studied at 1, 3, 5, 7 and 9 weeks of postnatal age. Body and diaphragm muscle weights were measured. Diaphragm strips were studied in an in vitro preparation to assess muscle contractile and endurance properties. Total diaphragm weight increased considerably, by a factor of 23 over the 9 week-period of study and was highly correlated with body weight (r = 0.93, P less than 0.01). However, the ratio of diaphragm-to-body weight decreased progressively with age. In comparison with those from older animals, diaphragms from 1 and 3 weeks old animals: (1) generated similar force normalized for muscle weight but a lower force normalized for fibre cross-sectional area (P less than 0.05), (2) had longer time-to-peak tension and one-half relaxation times (P less than 0.01) and (3) were more resistant to fatigue (P less than 0.01). The mechanisms underlying the diaphragm functional development were discussed.

Age Factors↗
PubMed1991

[Effects of halothane on the electrical activity of respiratory muscles in rats].

This study was designed to investigate the effects of halothane on the electrical activity of the respiratory muscles in rats. Indeed, halothane is known to reduce end-expiratory lung volume, both in man and in animal; this may be due to altered activity in the respiratory muscles. The electrical activity of the diaphragm, parasternal, intercostal and abdominal muscles were recorded using intramuscular electrodes in ten rats weighing between 400 and 450 g each. The rats were prepared under light halothane anaesthesia (tracheostomy, laparotomy, electrode positioning, plaster of Paris cast to impede leg movements). They were placed prone in a 20 1 plexiglass chamber, and allowed to awake. Thereafter halothane was vaporized in this chamber at a known concentration, until the animals no longer reacted to tail pinching. The measurements were carried out during the awake state, and under 2 vol % halothane. Muscle tone was assessed by the thickness of baseline inspiratory muscle activity at the end of expiration (maximally amplified raw electromyographic signals). The measurement of phasic electrical activity was carried out using peak inspiratory integrated electromyographic signals. Under halothane, phasic activity of the diaphragm was slightly reduced (p less than 0.05), whereas tonic activity remained unchanged. Parasternal intercostal muscle activity, both tonic and phasic, was also decreased during halothane anaesthesia (p less than 0.001). No phasic activity occurred in the abdominal muscles, but muscle tone was reduced during halothane administration (p less than 0.01). In rats, the decrease in intercostal muscle tone under halothane anaesthesia could play a major part in the fall in functional residual capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Multiple effects of BAY K 8644 and nifedipine on isolated diaphragmatic fibers in vitro.

The dose-response effects of BAY K 8644 and nifedipine on diaphragmatic contractility were assessed in vitro. Isolated diaphragmatic fibers were obtained from rats and placed in an open-topped channel of a Plexiglas tissue chamber perfused with continuously flowing Krebs solution heated to 37 degrees C. Isometric twitch force, generated in response to 1-Hz supramaximal electrical stimulation (4 times/min), was measured with a highly sensitive photoelectric force transducer. Low doses of BAY K 8644 or nifedipine (10(-7) M) were without effect on twitch tension. For 10(-6) M, twitch tension increased by 10 +/- 1% (P less than 0.005) for both drugs. For 10(-5) M, twitch tension increased by 12 +/- 1% (P less than 0.05), and maximal contractures were observed (BAY K 8644 and nifedipine). Simultaneous drug administration did not reveal mutual antagonism as expected; instead the effects were additive, with twitch tension increasing by 30 +/- 2% (P less than 0.001) for 10(-5) M BAY K 8644 + nifedipine. Both BAY K 8644 and nifedipine altered twitch characteristics. In low-calcium media (0.5 mM) twitch potentiation produced by the two drugs was further enhanced (increasing 60% for 10(-5) M BAY K 8644 or nifedipine). Contractures, by contrast, were abolished. From these results it is difficult to reconcile a unique action of these drugs on calcium channels as is conventionally accepted.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Protective effect of theophylline on bronchial hyperresponsiveness in patients with allergic rhinitis.

Disorders of the upper respiratory tract, particularly allergic rhinitis are commonly associated with bronchial hyperresponsiveness. The latter may be responsible for chronic cough, a common symptom in patients with allergic rhinitis, which, as previously shown, can be the sole presenting manifestation of bronchial hyperresponsiveness. Theophylline is widely used in patients with asthma for its bronchodilator effect, whereas its action on bronchial reactivity is controversial. The aim of this study was to determine the effect of theophylline administration on bronchial hyperresponsiveness in patients with allergic rhinitis complaining of chronic cough. Fourteen patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol, which decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. After control measurements patients received in a randomized, double-blind crossover fashion either theophylline 10 mg/kg/day orally or placebo for 30 days. Measurements were then redone. After a washout period of 8 days the measurements were repeated, and patients received theophylline or placebo for a second period of 30 days. Measurements were again performed at the end of this last study period. During control all patients had normal baseline lung function data and showed marked bronchial hyperresponsiveness, PD35 amounting to 26 +/- 7 micrograms of carbachol (normal value greater than 160 micrograms). No significant changes in PD35 were noted after placebo and washout when compared with control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Reimplantation of a non-functioning lung. Report of a case].

The authors present the case of a patient with a carcinoid tumor of the left main bronchus. Conservative surgery by sleeve resection without pulmonary resection was performed. The underlying lung which was considered to be nonfunctioning during pre-operative evaluations, completely recovered within a year following surgery.

Anastomosis, Surgical↗
PubMed1991

[The control of respiration in pulmonary fibrosis. The effect of O2 and CO2].

We have studied the mode of ventilation and chemosentivity in 10 patients suffering from pulmonary fibrosis. The total lung capacity was on average 63.5 +/- 8% of the predicted. Their static compliance was 0.078 +/- 0.05 l.cm of water. The patients were studied in the prone position breathing ambient air then on hyperoxia. The response to CO2 was assessed according to the rebreathing method of Read. The results of these patients were compared with those of 11 normal subjects. The ventilation at rest was normal, with a shortened respiratory time and a Ti/Ttot ratio which was lowered. The occlusion pressure (P0.1) was very much higher than that in normal subjects. This rise was correlated with an increase in pulmonary elastance and a reduction in vital capacity. The correction of hypoxia was without effect on the respiratory parameters. In relation to normal subjects the ventilatory response to carbon dioxide in fibrotics was decreased whilst the response of the P0.1 was increased expressing central hyperactivity. In conclusion, fibrotic patients have normal ventilation in spite of an increase in inspiratory work. This normal ventilation results from hyperactivity of the respiratory centre, as in the hyperventilation induced by carbon dioxide when at rest.

Adult↗
PubMed1990

A preparation for in vivo study of the diaphragmatic microcirculation in the rat.

A new preparation is described for the study of the microcirculation of the rat diaphragm by in vivo microscopy. After midline laparotomy, the abdominal site of the diaphragm muscle was exposed. The rat was mechanically ventilated and placed in the Trendelenburg position, thus allowing a microscope placed on a three-dimensional articulated system to be set up perpendicular to the diaphragm. The diaphragm was then transilluminated by inserting fiberoptic microprobes into the thorax cavity by thoracotomy in the fifth intercostal space. This preparation allowed us to describe the morphological characteristics of the arteriolar network in vivo. As regards the venular network, two parts were distinguished: one part collects the blood of the external half of the diaphragm, runs roughly parallel to the arterioles, and converges toward the internal mammary and intercostal veins; the other part collects the blood of the central half of the diaphragm and converges on the central venous arcade along its central tendon. Anastomotic channels between these two parts were observed, as well as spontaneous inversion of the direction of the blood flow, indicating the presence of unsteady pressure gradients in some branches of the venular network. Capillary density was also studied by measuring intercapillary distance, whose mean value was 21.43 +/- 0.67 microns. No differences in intercapillary distance were found between the external and central parts of the diaphragm. In conclusion, we describe a preparation which allowed us to study the diaphragmatic microcirculation for at least 2 hr under good hemodynamic conditions. The study of this specific microcirculation is important because the diaphragm's metabolism and functions are specific and because it is essential to life that its perfusion should be adapted to its specific metabolic requirements.

Animals↗