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Biomedical subjects

C Grimaud

Publications and source records attributed to C Grimaud.

At least 19 recordsLinked to original sources

Role of vagal and spinal sensory pathways in diaphragmatic response to resistive loading.

The effects of severe inspiratory (I) or expiratory (E) resistive loads on diaphragmatic activity were studied in two groups of cats anaesthetized with sodium pentobarbital or ethylcarbamate-chloralose. In intact cats, I or E loading never changed the amplitude of integrated diaphragmatic electric myogram (EMG) measured at 1.0 s (Edi 1.0); only I loading, prolonged the duration of diaphragmatic activity (Tdi). After selective procaine block of non-volume related vagal sensory inputs, I or E loading markedly increased Edi 1.0 and changes in Tdi due to I loading persisted. After bivagotomy, which also suppressed volume related vagal feed back, Edi 1.0 increased during I or E loading but change in Tdi disappeared. Initial spinal section at C8 level only reduced changes in Tdi with inspiratory loading. Bivagotomy plus spinal section abolished all load induced changes in diaphragmatic activity. These results suggest that all vagal information from the lungs participate in the mechanism of load compensation but that spinal sensory pathways play a minor role in this response in anaesthetized cats.

Afferent Pathways

Laryngeal afferents activated by phenyldiguanide and their response to cold air or helium-oxygen.

In anesthetized cats, sensory neurons in the superior laryngeal nerves (SLN) were identified with respect to their response to (1) phenyldiguanide (PDG) i.v., (2) mechanical stimulation and (3) lowering temperature in an isolated tracheolaryngeal segment. The activity originating from 107 SLN afferent units activated by PDG was recorded using glass microelectrodes advanced in the nodose ganglion. All tested afferent units increased their discharge rate during direct touching of the airway mucosa. None showed flow or pressure related activity during abrupt changes in constant laryngeal flow or transmural pressure in the isolated segment. Fifteen units were inhibited by cold air. Sixty-two units significantly increased their firing rate when the temperature approached 18 degrees C, reached a peak discharge near 15 degrees C, then their activity decreased or stopped. The response to cold air was compared to cold heliox (79% He-21% O2), which enhanced the respiratory heat loss by conduction. The peak firing rate was significantly higher with heliox (+356% compared to +246% with air), the temperature threshold higher (25 degrees C +/- 1.0 degree C) and the temperature range broader (25-11.5 degrees C). Present results show that a large proportion (58%) of afferent SLN fibres activated by PDG are likely non-proprioceptive units, which are stimulated by cooling the inspired gas. Thermosensitive units in the upper airways may act as sensors of the thermal flux through the airway wall more than as detectors of the absolute value of temperature in the airway lumen.

Action Potentials

The effects of ischemia, lactic acid and hypertonic sodium chloride on phrenic afferent discharge during spontaneous diaphragmatic contraction.

In 9 sodium pentobarbital anaesthetized cats, 50 single-unit phrenic afferent recordings were determined during spontaneous ventilation, retrograde carotid arterial injection of lactic acid (LA, 0.1 N) and NaCl (5%), and a 2-min occlusion of the superior thoracic aorta. Fifty percent of the units had tonic low-frequency spontaneous discharge; 50% had phasic high-frequency discharge. Tonic fiber activity increased significantly with LA, NaCl and occlusion, while phasic fiber activity decreased in all 3 conditions. These results suggest that the diaphragm contains sensory endings sensitive to ischemia and extracellular metabolic changes.

Animals

Cold-induced bronchospasm in normal and sensitized rabbits.

In anesthetized, paralyzed and artificially ventilated rabbits, changes in lung resistance induced by cooling the inspired air were studied under dry air conditions. Airway response to cold was measured in normal animals and in rabbits sensitized to bovine serum albumin. The magnitude of cold-induced bronchospasm was significantly greater in sensitized than in normal rabbits but the time course for recovery of control lung resistance during rewarming was the same in both groups and lasted longer than 4 min. Inhalation of a nebulized aerosol of sodium cromoglycate (SCG) markedly reduced cold-induced bronchospasm and shortened the recovery period, which then lasted only 20 to 30 sec. Vagotomy abolished the airway response to cold air in all cases and this was observed whether the vagus nerves were cut before or after SCG inhalation. SCG or vagotomy exerted the same effect on the response to cold air in normal or sensitized rabbits. Sensitized animals showed an hyperresponsiveness to histamine as well as to cold air. These results suggest that cold-induced bronchospasm results from a vagally mediated reflex whose effects are only enhanced and prolonged by a local release of humoral factors, linked to the reflex path. The increased response to cold air in the sensitized rabbits seems to correspond to non-specific hyperresponsiveness of bronchial smooth muscle rather than to an increased local release of inflammatory mediators.

Aerosols

Role of vagal and spinal sensory pathways on eupneic diaphragmatic activity.

The interactions between vagal and spinal afferents in the control of eupneic diaphragmatic activity were studied in two groups of cats anesthetized either with pentobarbital sodium (SPB) or with ethyl carbamate-alpha-chloralose (ECC), which enhanced spinal reflexes. Under both conditions of anesthesia two experimental protocols were performed: 1) bilateral cervical vagotomy followed by spinal section at C8 level or 2) spinal section followed by vagotomy. Changes in integrated diaphragmatic activity (Edi) were studied during eupneic ventilation and tracheal occlusion at end expiration. Vagotomy always significantly increased the amplitude of Edi during eupnea (SPB + 30%; ECC + 15%) and prolonged its duration (Tdi) (SPB + 110%; ECC + 75%) but did not modify the overall shape of the Edi vs. time relationship. Spinal section induced reverse changes in the amplitude of Edi, whether vagal afferents were present or suppressed and modified the shape of the Edi wave, but did not significantly modify Tdi. These results indicate that both vagal and spinal afferents may participate in the control of eupneic inspiration but exert different and interdependent influences on the recruitment and firing time of phrenic motoneurons. In addition, Tdi measured during tracheal occlusion (Todi) was markedly prolonged under ECC anesthesia. In this situation spinal section reduced Todi, which became close to the values obtained in intact or spinal cats under SPB anesthesia. Thus the response to tracheal occlusion at end expiration cannot be interpreted as resulting from the sole suppression of volume related vagal information.

Afferent Pathways

Phrenic afferents and their role in inspiratory control.

In anesthetized cats, with vagi cut and the spinal cord severed at the C8 level, phrenic motor and/or sensory discharge was recorded. Small afferent phrenic fibers were identified through their activation by lactic acid, hyperosmotic NaCl solution, or phenyl diguanide. They exhibited a spontaneous but irregular low-frequency discharge. Block of their conduction by procaine had no effect on eupneic motor phrenic activity. Large afferent phrenic fibers showed a spontaneous rhythmic discharge, and cold block (6 degrees C) of these fibers significantly prolonged the phrenic discharge time (Tphr) and total breath duration (TT) during eupnea. The stimulation of all afferent phrenic fibers lowered the impulse frequency of phrenic motoneurons (f impulses) and shortened both Tphr and TT. When the stimulation was performed during cold block all of the effects on phrenic output persisted, but changes in timing were less pronounced. Under procaine block, only the effects of phrenic nerve stimulation on Tphr persisted. These results suggest that both large and small afferent phrenic fibers control the inspiratory activity with a prominent role of small fibers on phrenic motoneuron impulse frequency.

Afferent Pathways

Pulmonary function and electromyographic study of respiratory muscles in myotonic dystrophy.

Ten adult myotonic dystrophy patients underwent measurements of lung function, maximal dynamic and static ventilatory efforts, and respiratory muscle electromyography (EMG). EMG studies were performed during spontaneous breathing or when subjects breathed through high inspiratory or expiratory resistive loads. Present results show that (1) a moderate restriction of lung volumes with hypoxemia plus normocapnia is often observed; (2) patients sustain dynamic ventilatory efforts more easily than static work; and (3) abnormalities in respiratory muscle EMG exist with spontaneous expiratory and inspiratory intercostal activities during quiet breathing and changes in muscular response to resistive loads. Inspiratory loading evokes contraction of expiratory muscles, with a marked decrease in inspiratory activities. Expiratory resistive loads prolong the diaphragmatic contraction throughout the expiratory time, and in some patients, relaxation of the diaphragm does not occur during the loaded run. These EMG data suggest that the reciprocal inhibition among respiratory neurons is enhanced in myotonic dystrophy and that myotonia also occurs in the diaphragm when loads oppose its relaxation.

Adult

Inspiratory and expiratory resistive load detection in normal and asthmatic subjects. A sensory decision theory analysis.

The ability to detect added external inspiratory and expiratory resistive loads was studied in normal and asthmatic subjects using sensory decision theory as a psychophysical method. Performances P(A)/delta R [where P(A) represents the index of sensitivity and delta R the additional resistor] were similar in normal and asthmatic subjects, but when sensitivity was expressed in relation to airway resistance [P(A)/delta R/Raw], asthmatics showed higher inspiratory and expiratory performances than normal subjects. After bronchodilation the relative sensitivity in the asthmatic group was impaired and approached that of normal subjects. Comparing inspiratory and expiratory load detection, normal subjects showed a higher sensitivity for expiratory than for inspiratory loads. In contrast, there was no difference in the asthmatic group. The response bias remained the same across conditions. If one accepts the assumption that the variability of sensitivity presented by asthmatic and normal subjects might be related to the variable state of their pulmonary function, our results can be interpreted as demonstrating a relationship between sensitivity and pulmonary distension or airway obstruction. These results are in agreement with the hypothesis that the site of perception for respiratory load detection is the chest wall.

Adolescent

Ventilatory effects of domperidone, a new dopamine antagonist, in anaesthetized rabbits.

The ventilatory effects of domperidone (DP), a dopamine antagonist that does not cross the blood-brain barrier, were studied on rabbits anaesthetized with pentobarbitone. DP induced hyperventilation (+20%), which was not dose-dependent, without any marked change in arterial blood gases. This effect was abolished by previous transection of both carotid sinus nerves. On an average, steady state hypoxia (PaO2 approximately 45 mmHg for 5 min) doubled ventilation before, and increased itself threefold after DP (0.10 mg kg-1 i.v.). Prazosin (PZ, 0.1 mg kg-1 i.v.), an alpha 1-adrenoceptor antagonist, induced hyperventilation (+16%) but decreased systemic arterial blood pressure. PZ did not modify the ventilatory response to steady state hypoxia. In short, DP has a slight stimulating effect on resting ventilation and potentiates the ventilatory response to steady state hypoxia. This last effect would not depend on additional alpha 1-adrenoceptor antagonism of DP, as PZ does not change the ventilatory response to hypoxia.

Anesthesia

[Influence of chronic smoking on leukocytes].

The authors showed a significant increase in total leukocyte count (2p less than 0.001), neutrophil concentration (2p less than 0.001) and lymphocyte concentration (2p less than 0.01) in 21 chronic smokers compared to 22 non-smokers. However, only the total leukocyte count and the neutrophil count proved to be correlated to carboxyhemoglobin saturation. Slightly different hypotheses are proposed to explain the increase in leukocyte count: the carbon monoxide and/or the carboxyhemoglobin acts directly on peripheral blood leukocytes or indirectly, via the adrenalin secretion. The average leukocyte count in smokers corresponds to the upper borderline in nonsmokers; therefore, it seems pertinent to take into consideration the number of cigarettes smoked per day when assessing a smoker's leukocytosis.

Carboxyhemoglobin

[Equipment of a water spirometer with a view to automation of spirometry].

This work describes the complete automatisation of spirometry, the basic examination when assessing respiratory function. The movements of a water spirometer bell, transformed into electrical signals, are transmitted to a micro-computer, equipped with a digital analogue interface and then analysed. A few seconds after the performance of the examination the complete results are automatically edited in absolute values and as a percentage of predicted values (CECA). They are compared to previous calculations in the same spirometer, using the usual technique. The correlations obtained between the two series of results (145 examinations) show the reliability of the automated technique both for calculating volumes as for the maximal expired flows. In conclusion, while conserving the standard information in spirometry, the automatisation of this exam allows a considerable saving of time.

Computers

Airway response of asthmatics to carbachol and to deep inspiration.

Dose-response curves were established in asthmatics by using graded doses of aerosolized carbachol and specific airway conductance (SGaw) measurements. After carbachol inhalation, we evaluated the influence on SGaw of a deep inspiration to total lung capacity followed by a passive expiration to functional residual capacity. When SGaw had returned to its pre-deep-inspiration value, forced expiratory volume in one second (FEV1) was obtained. Two groups of patients were selected according to the effect of deep inspiration on SGaw: group A (22 patients) with a less than 25% SGaw increase after deep inspiration, and group B (21 patients) with a more than 75% SGaw increase. Both groups were comparable in age and initial SGaw and FEV1 values. Carbachol inhalation induced a similar SGaw decrease in both groups, whereas FEV1 decreased more (p less than 0.05) in group A than in group B. The two groups did not differ significantly regarding the dose of carbachol causing a 25% SGaw decrease and in the slope of the dose-response curve. We conclude that, in asthmatic patients, airway response to an inhaled broncho-constrictor agent is not related to the airway response to deep inspiration. This suggests that previous studies of airway response to bronchoconstrictor agents which have been performed by using only FEV1 measurements, may need to be reassessed.

Adult

Changes in activity of vagal bronchopulmonary C fibres by chemical and physical stimuli in the cat.

1. In eighteen anaesthetized cats, action potentials in non-myelinated vagal afferent neurones were recorded in the nodose ganglion by means of extracellular micro-electrodes. 2. The pulmonary or bronchial origin of these C fibres was assessed in closed chest preparations by injecting phenyl diguanide into either the right atrium or the ascending aorta (bronchial circulation). This was confirmed in two animals by local mechanical stimulation. 3. Eighty per cent of bronchopulmonary C fibres increased their discharge frequency when the end-tidal CO2 concentration (FA,CO2) increased from 0.02 to 0.10. Most of these C endings showed a maximal response when FA,CO2 reached 0.04. For the others a further increase in discharge occurred when CO2 concentration reached 0.08-0.10. Continuous measurement of C fibre discharge frequency indicated that they detected preferentially changes in the inspired CO2 content, but adapted when a high CO2 level was maintained. Their activation by hypercapnia was followed by an increase in lung resistance. 4. Lowering the O2 content of the inspired gas had no effect on the spontaneous activity of bronchopulmonary C endings. 5. When the stroke volume of the pump was doubled, the spontaneous activity of bronchopulmonary C fibres decreased in intact chest preparations. Inflation of the lungs had the opposite effect after the chest was opened. In both cases hyperdeflation was a potent stimulus to these receptors. 6. In tracheotomized cats, the tracheal temperature was 28-29 degrees C. When normal thermal conditions were restored in the tracheal lumen (33-34 degrees C) the spontaneous discharge frequency of some bronchial C fibres was greatly increased. 7. It is concluded that the spontaneous activity of most of the bronchial or pulmonary C fibres was maximal when chemical and physical physiological conditions were restored in the lungs. It appears that changes in alveolar CO2 concentration constitute the usual stimulus for these fibres.

Action Potentials

Ventilatory responses to muscular vibrations in healthy humans.

In healthy humans, we studied the effect of high-frequency mechanical vibrations applied unilaterally to the tendon of the biceps or triceps brachialis on ventilation and the breathing pattern. This stimulus preferentially activates the muscle spindle afferents. Increase of respiratory frequency and changes in the ventilatory timing started at the first or second inspiration during tendon stimulation, and no adaptation occurred as long as the vibrations continued. The tidal volume and mean inspiratory flow rate were only enhanced in individuals having high-frequency breathing during eupnea. The changes in ventilatory variables were observed when the motor response to vibrations was tested under isometric or isotonic conditions. Various experimental procedures enabled us to induce a tonic reflex contraction in either the vibrated muscle or the antagonist of no reflex contraction in either group of muscles. In all cases the increase in minute ventilation was identical. These changes in breathing pattern was not associated with a significant decrease in alveolar CO2 pressure and did not seem to be responsible for important variations in respiratory gas exchanges. The response to high-frequency vibrations was also studied after ventilation was increased with added dead space. The magnitude of hyperventilation an the pattern of ventilatory response produced by tendon stimulation did not change with increased ventilation. In conclusion, the stimulation of muscle spindles in human induces changes in ventilation and pattern of breathing , and the occurrence of a reflex muscular contraction does not seem necessary in order to obtain such effects.

Adult

Influence of anxiolytic drugs (Prazepam and Diazepam) on respiratory center output and CO2 chemosensitivity in patients with lung diseases.

Occlusion pressure at 0.1 s (P0.1) and its evolution during progressive hyperoxic hypercapnia (CO2 chemosensitivity) were measured in 40 patients. Most of them (26) were affected by asthma and /or chronic bronchitis and had mild obstruction and hypoxemia. Measurements were made after 2 days of oral prazepam, diazepam or a placebo (single-blind study). Diazepam induced a significant decrease in P0.1 without affecting CO2 chemosensitivity. In contrast, prazepam did not significantly modify P0.1 or CO2 chemosensitivity. However, P0.1 decreased in 5/18 individual cases. 1 week of treatment by prazepam has advantages over diazepam by not depressing respiratory center output.

Asthma