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.

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.

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.

Effects of airflow resistance variations on resistive load detection in normal subjects.

The sensitivity to airflow resistance variations produced by externally added resistive loads, with modification of background load, was studied in 15 normal subjects, using "Sensory Decision Theory" (SDT), a psychophysical method that gives an index of accuracy, P(A), unaffected by response bias. In six subjects, asked to detect three increasingly added loads (delta R) at different levels of basal resistance (1.6 and 3.6 cmH2O X 1(-1) X s), inspiratory resistive load detection (RLD) improved with background loading, and a highly significant relationship was found between P(A) and peak mouth pressure (Pm). The relationship between P(A) and the change in Pm, i.e. delta Pm, was less significant. These results suggest that, although tension developed by the respiratory muscles reflected by mouth pressure may be an important stimulus to respiratory RLD, other factors must also be considered. In seven subjects, in whom airway resistance was increased at least 50% by inhalation of carbachol, inconsistent variations in P(A) were found. In seven subjects, in whom airflow resistance was decreased by inhalation of heliox, and in six of seven subjects after salbutamol inhalation, RLD was significantly impaired. The results of this study lead us to the conclusion that Weber's law is not verified for weak internal or external background loading.

Breathing discomfort in asthma: role of adaptation level.

In asthmatic patients, Helson's adaptation level theory was applied to breathing discomfort to investigate the discrepancy between the subjective severity of breathlessness and their objective airflow obstruction. The data from a signal detection methodology show a considerable loss of sensitivity in twelve asthmatic patients with permanent airflow obstruction compared to the high sensitivity of six normal subjects to the same four external resistive loads (range 2.5 to 8.0 cmH2O X l-1 X s). Furthermore, when subjective ratings are examined, the absence of any contrast effect between adjacent load intensities in asthmatics suggests that these subjects evaluate the discomfort induced by the loads with reference to a strong internal comparison (adaptation level) rather than to the experimental stimuli. There was no relationship between physiological parameters and the low sensitivity of asthmatics. Also salbutamol-induced bronchodilation in six asthmatics did not improve sensitivity or induce any contrast effect. These two observations bring out the necessity to consider the role of past experience of breathing discomfort on adaptation level and sensitivity.

[Assessment of the reflex vagal origin of broncho-constrictor effects of hypercapnia in cats (author's transl)]. / Mise en évidence de l'origine vagale réflexe des effets bronchoconstricteurs du CO2 chez le chat.

Breath-by-breath measurements of pulmonary resistance (RL) were used to study the bronchomotor effects produced by the inhalation of a CO2-enriched gas mixture in anaesthetized, spontaneously breathing cats. A significant increase in RL occurred from the second inhalation of the hypercapnic gas mixture. This bronchoconstrictor effect lasted about 18 seconds, then a marked decrease in RL was observed. The secondary bronchodilatation persisted during the entire hypercapnic test (4 min). After surgical suppression of the sensory vagal component at the level of the nodose ganglion (bilateral sensory vagotomy), the early bronchoconstrictor effect of CO2 disappeared, but the secondary bronchodilatation was unchanged. In other experiments, after procaine block of the nervous conduction in non-myelinated vagal fibers, the bronchomotor effects of CO2 were the same as those observed after sensory vagotomy. In contrast, an electrotonic block of both vagus nerves, which abolished nervous conduction in myelinated fibers, did not suppress the bronchoconstrictor response to hypercapnia. Thus, the early increase in RL, which follows inhalation of a hypercapnic gas mixture, seems to be reflexly mediated by vagal afferents, especially by non-myelinated fibers.

[Effects of medullary pyramidal stimulation on myocardial contractility in anesthetized dogs]. / Effets de la stimulation des pyramides bulbaires sur la contractilité myocardique chez le chien narcosé.

In anaesthetized dogs, medullary pyramid stimulation produces a decrease of myocardial contractility. The peak of the first derivative of the left ventricular pressure (dP/dt max) was used to assess myocardial contractility; this index is independent of afterload. Medullary pyramid stimulation produces a decrease of dP/dt max and of the maximal left ventricular pressure (L.V.P. max) also, after bilateral vagotomy. But the same stimulation induces only a decrease of L.V.P. max after inhibiting beta-adrenergic efferences and bilateral vagotomy. Just as corticopyramidal fibres inhibiting alpha-adrenergic vascular tone, one does consider the existence of corticopyramidal fibres inhibiting beta-adrenergic efferences to myocardium.

Suprathreshold resistive load perception in normal and asthmatic subjects.

The perception of external suprathreshold loads (2.5-44 cm H2O.1-1.s) was determined in 5 normal and 16 asthmatic subjects in order to (1) study the role of the wording given to the subject for rating the inspiratory loads, either 'intensity' or breathing 'discomfort', and (2) compare the sensation to low (2.5-8 cm H2O.1-1.s) and to high (17-44 cm H2O.1-1.s) loads. Normal subjects exhibited accurate rating of the loads regardless of the wording; high loads were estimated as more severe than the low ones, in spite of a long time interval between the two experiments. They were able to discriminate between each pair of loads. On the contrary, asthmatics with chronic airway obstruction demonstrated a poor perception in all experimental conditions. The physiological variables of breathing pattern and mouth pressure were modified in the same manner in the two populations and could not account for the differences in perception. In conclusion, the differences in sensitivity observed between normal and asthmatic subjects were verified for suprathreshold load perception whatever the wording and the level of the loads. Therefore, for this kind of experimental study, it is not useful to study the full scale of the loads. Furthermore, the present methodological approach provides an additional support to the assumption that the asthmatics' poor sensitivity is related to psychological factors such as past experience of loaded breathing.

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.