Electrical stimulation of arterial and central chemosensory afferents at different times in the respiratory cycle of the cat: II. Responses of respiratory muscles and their motor nerves

The response patterns of the electrical activity of the respiratory motor nerves and muscles to brief electrical stimulation of the arterial and the intracranial chemosensory afferents were studied in anesthetized cats. Stimulation during inspiration increased the activity of phrenic nerve and the inspiratory muscles (intercostal, diaphragm) with a latency of 15–25 ms, whereas expiratory muscle activity in the following expiration remained almost unaltered. Stimulation during expiration increased the activity of expiratory nerves and muscles (intercostal, abdominal) after a delay of 80–120 ms. The later the stimulation occurred in the insor expiratory period the larger the increase in amplitude and in steepness of rise of the respective integrated activity in respiratory nerves and muscles. Stimulation in early inspiration shortened the discharge period of inspiratory muscles, whereas excitation in early expiration caused an earlier onset and prolonged the activity in the expiratory muscles. Stimulation in the late phase of ins- or expiration prolonged the discharge of the respective nerves and muscles. Both the arterial (carotid sinus nerve, CSN, and aortic nerve, AN) and intracranial chemosensory (VM) afferents stimuli were able to affect both the inspiratory and the expiratory mechanisms. The restriction of the effects to the phase of the stimulus suggests a mechanism by which these afferents, when activated during inspiration, effectively project only to inspiratory neurones, and vice versa for expiration.Supported by the Deutsche Forschungsgemeinschaft, SFB 114 Bionach     

Mechanical effect of muscle spindles in the canine external intercostal muscles

High-frequency mechanical vibration of the ribcage increases afferent activity from external intercostal muscle spindles, but the effect of this procedure on the mechanical behaviour of the respiratory system is unknown. In the present study, we have measured the changes in external intercostal muscle length and the craniocaudal displacement of the ribs during ribcage vibration (40 Hz) in anaesthetized dogs. With vibration, external intercostal inspiratory activity increased by ∼50 %, but the respiratory changes in muscle length and rib displacement were unaltered. A similar response was obtained after the muscles in the caudal segments of the ribcage were sectioned and the caudally oriented force exerted by these muscles on the rib was removed, thus suggesting that activation of external intercostal muscle spindles by vibration generates little tension. Prompted by this observation, we also examined the role played by the external intercostal muscle spindles in determining the respiratory displacement of the ribs during breathing against high inspiratory airflow resistances. Although resistances consistently elicited prominent reflex increases in external intercostal inspiratory activity, the normal inspiratory cranial displacement of the ribs was reversed into an inspiratory caudal displacement. Also, this caudal rib displacement was essentially unchanged after section of the external intercostal muscles, whereas it was clearly enhanced after denervation of the parasternal intercostals. These findings indicate that stretch reflexes in external intercostal muscles confer insufficient tension on the muscles to significantly modify the mechanical behaviour of the respiratory system.     

The output from human inspiratory motoneurone pools

Survival requires adequate pulmonary ventilation which, in turn, depends on adequate contraction of muscles acting on the chest wall in the presence of a patent upper airway. Bulbospinal outputs projecting directly and indirectly to 'obligatory' respiratory motoneurone pools generate the required muscle contractions. Recent studies of the phasic inspiratory output of populations of single motor units to five muscles acting on the chest wall (including the diaphragm) reveal that the time of onset, the progressive recruitment, and the amount of motoneuronal drive (expressed as firing frequency) differ among the muscles. Tonic firing with an inspiratory modulation of firing rate is common in low intercostal spaces of the parasternal and external intercostal muscles but rare in the diaphragm. A new time and frequency plot has been developed to depict the behaviour of the motoneurone populations. The magnitude of inspiratory firing of motor unit populations is linearly correlated to the mechanical advantage of the intercostal muscle region at which the motor unit activity is recorded. This represents a 'neuromechanical' principle by which the CNS controls motoneuronal output according to mechanical advantage, presumably in addition to the Henneman's size principle of motoneurone recruitment. Studies of the genioglossus, an obligatory upper airway muscle that helps maintain airway patency, reveal that it receives simultaneous inspiratory, expiratory and tonic drives even during quiet breathing. There is much to be learned about the neural drive to pools of human inspiratory and expiratory muscles, not only during respiratory tasks but also in automatic and volitional tasks, and in diseases that alter the required drive.     

Anatomical model of the human trunk for analysis of respiratory muscles mechanics

A realistic two-dimensional (2D) model of the human trunk was developed for quantitative analysis of the relative contribution to breathing mechanics of seven groups of respiratory muscles. Along with noninvasive measurements of electromyography (EMG) signals from respiratory muscles near the skin surface, it provides predictions for the forces generated by inner respiratory muscles as well as the instantaneous work of each muscle. The results revealed that inspiratory muscles reach their maximal force towards the end of inspiration, while expiratory muscles reach their maximal force at mid-expiration. Inspiratory muscles contributed to the work of breathing even at low efforts, while that of the expiratory muscles was observed only at relatively high efforts. The study clearly showed that the diaphragm muscle generates forces, which are of the same order as those generated by other inspiratory muscles, but performed 60-80% of the inspiratory work. The contribution of the external intercostal muscle to inspiration was not negligible, especially at high breathing efforts.     

Are the external and internal intercostal muscles synergist or antagonist in the cat?

The electrical activity of the external and internal intercostal muscles was recorded in decerebrated cats during eupnea and in the course of dyspnoea artificially induced to reinforce the inspiratory or expiratory central drive. In the cephalic part of the thorax (1st-5th ribs) the lateral part of the external and internal intercostal muscles are synergist and inspiratory. In the caudal part of the thorax (9th-13th ribs) these muscles are also synergist but expiratory. In the intermediate part (5th-9th ribs) the intercostal muscles are antagonist, the external ones are inspiratory and the internal ones are expiratory.     

Influences of lung mechanoreceptors and carotid chemoreceptors on the response of respiratory muscle activity to tracheal occlusion

We examined the responses of respiratory muscle electromyograms (EMGs) from internal (IIC) and external intercostal (EIC) muscles and diaphragm (DIAP) to three successive occluded breaths in anesthetized spontaneously breathing rabbits. Both inspiratory and expiratory muscle EMGs progressively increased in the course of tracheal occlusion. An increase in these muscle EMGs was still observed after release of tracheal occlusion, but those effects were short-lasting. In a separate series of experiments, for assessment of possible reflex effects involved, the responses of slowly adapting pulmonary stretch receptor (SAR), rapidly adapting pulmonary stretch receptor (RAR), and carotid chemoreceptor activities to tracheal occlusion lasting for three respiratory efforts were also examined. The inspiratory discharge of SARs decreased but the expiratory discharge of SARs increased during tracheal occlusion. Although carotid chemoreceptors increased their activity in the latency of 3-6s after the onset of tracheal occlusion, the activity of RARs was greatly reduced throughout the period of tracheal occlusion. A transient increase in both carotid chemoreceptors and RARs was still observed after release of tracheal occlusion. These results suggest that alterations of inspiratory and expiratory muscle EMGs produced by tracheal occlusion would appear to be mediated by the afferent inputs from lung mechanoreceptors and carotid chemoreceptors.     

Effect of stimulation of the medial and lateral zones of the respiratory center on electrical activity of the diaphragm,intercostal muscles,and phrenic neurons

Experiments on cats showed that the nucleus of the tractus solitarius contains zones during stimulation of which electrical activity of the phrenic neurons and diaphragm is selectively stimulated or inhibited. Stimulation of inspiratory and expiratory zones of the nucleus ambiguus influences the electrical activity of the external intercostal muscles. During stimulation of the corresponding zones in the gigantocellular nucleus electrical activity is changed in both groups of inspiratory muscles simultaneously. It is postulated that the action of stimulation of the zones of the gigantocellular nucleus on both groups of inspiratory muscles is indirect in its mechanism, through neurons of the nucleus of the tractus solitarius and nucleus ambiguus.Academy of Medical Sciences of the USSR Group, Kuibyshev Medical Institute. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 4, pp. 392–395, April, 1978.     

Maximal activation of the human diaphragm but not inspiratory intercostal muscles during static inspiratory efforts

It is widely held that transdiaphragmatic pressure is a reliable index of the extent of central activation of the diaphragm but the maximal voluntary transdiaphragmatic pressure is lower during inspiratory than expulsive efforts. To determine whether the diaphragm is fully activated during the two manoeuvres supramaximal stimuli were delivered to both phrenic nerves during maximal efforts. No discernible twitch was evoked during 30-55% of attempted maximal efforts with either voluntary manoeuvre. Thus the difference in maximal transdiaphragmatic pressure between the manoeuvres must reflect changes in chest-wall geometry or mechanics rather than in the phrenic motor outflow. Inspiratory intercostal muscle activity was consistently submaximal during maximal inspiratory efforts.     

The role of the fusimotor system with respect to the contribution of the diaphragm and the intercostal muscles to the respiratory tidal volume

Summary The efferent electrical activity in the phrenic nerve can be quantified in such a way that it gives a good correlation to tidal volume. After administration of the drug benzoctamine this relationship changes: more phrenic nerve activity is needed for the same tidal volume. No changes were found in the neuro-muscular transmission from the phrenic nerve to the diaphragm. There was no alteration in dynamic compliance of the lungs or in airway resistance. The afferent phrenic nerve activity from proprioceptors in the diaphragm did not change. It seems unlikely that respiratory neurons in the brainstem were affected since the sensitivity of the respiratory system to CO₂ did not change.It is known that the tonic fusimotoneuron activity is suppressed at a supraspinal level by benzoctamine. Since intercostal muscles have muscle spindles and the diaphragm hardly has any, the intercostal muscle activity will be affected more than diaphragmatic activity by benzoctamine. This could actually be shown by quantifying the electromyogram of inspiratory external intercostal muscles.The tidal volume regulation is controlled by the vagal feedback loop. In order to reach a certain tidal volume after administration of benzoctamine, the contribution of the diaphragm has to increase because the activity of the intercostal muscles is diminished.     

Effects of sleep on the tonic drive to respiratory muscle and the threshold for rhythm generation in the dog.

1. The present study was designed to determine the effect of sleep on the tonic output to respiratory muscle and on the level of chemical respiratory stimulation required to produce rhythmic respiratory output. 2. Chronically implanted electrodes recorded expiratory (triangularis sterni) and inspiratory (diaphragm and parasternal intercostal) electromyographic (EMG) activities in three trained dogs during wakefulness and sleep. The dogs were mechanically hyperventilated via an endotracheal tube inserted into a permanent tracheostomy. During the studies, a cold block of the cervical vagus nerves was maintained to avoid the complicating effects of vagal inputs on respiratory drive and rhythm. 3. During wakefulness, steady-state hypocapnia (partial pressure of CO2, PCO2 = 30 mmHg) abolished inspiratory EMG activity, resulting in apnoea, but the expiratory muscle became tonically active. Compared to wakefulness, the level of the tonic expiratory EMG activity was decreased in non-REM (non-rapid eye movement) sleep (median decrease = 34%, P = 0.005) and was further decreased in REM sleep (median decrease = 78%, P < 0.0001). During REM sleep, the tonic expiratory EMG activity was highly variable (mean coefficient of variation = 39% compared to 7% awake, P < 0.0001) and in some periods of REM, bursts of inspiratory EMG activity and active breathing movements were observed despite the presence of hypocapnia. 4. During constant mechanical hyperventilation, progressive increases in arterial PCO2 (in hyperoxia) were produced by rebreathing. Measurement of the CO2 threshold for the onset of spontaneous breathing showed that this threshold was not different between wakefulness and non-REM sleep (mean difference = 0.1 mmHg from paired observations, 95% confidence interval for the difference = -1.0 to +1.1 mmHg, P = 0.898). 5. The results show that sleep reduces the tonic output to respiratory muscles but does not increase the CO2 threshold for the generation of rhythmic respiratory output. These observations suggest that changes in the tonic drives to the respiratory motoneurones may be a principal mechanism by which changes in sleep-wake states produce changes in respiratory output.     

Descriptive ventilatory mechanics from noninvasive analog display of ribcage and abdominal flow

A rapidly responding analog display of ventilatory flow at the mouth, ribcage and abdomen allows interpretation of the relative activity of the diaphragm, accessory inspiratory muscles and abdominal expiratory muscles. These relative movements are exaggerated by having volunteers perform the ventilatory maneuvers of sniff, rapid exhalation and cough. Activity and regional lung flow can change in time periods in the tens of milliseconds. These rapid (within an inspiratory or expiratory time) relational changes in respiratory muscle activity and regional lung flow have not previously been demonstrated with a simple noninvasive measurement.     

Respiratory muscle strength and cough capacity in patients with Duchenne muscular dystrophy

The function of inspiratory muscles is crucial for effective cough as well as expiratory muscles in patients with Duchenne muscular dystrophy (DMD). However, there is no report on the correlation between cough and inspiratory muscle strength. To investigate the relationships of voluntary cough capacity, assisted cough techniques, and inspiratory muscle strength as well as expiratory muscle strength in patients with DMD (n= 32). The vital capacity (VC), maximum insufflation capacity (MIC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were measured. Unassisted peak cough flow (UPCF) and three different techniques of assisted PCF were evaluated. The mean value of MICs (1918 +/- 586 mL) was higher than that of VCs (1474 +/- 632 mL) (p < 0.001). All three assisted cough methods showed significantly higher value than unassisted method (212 +/- 52 L/min) (F = 66.13, p < 0.001). Combined assisted cough technique (both manual and volume assisted PCF; 286 +/- 41 L/min) significantly exceeded manual assisted PCF (MPCF; 246 +/- 49 L/ min) and volume assisted PCF (VPCF; 252 +/- 45 L/min) (F = 66.13, p < 0.001). MIP (34 +/- 13 cmH2O) correlated significantly with both UPCF and all three assisted PCFs as well as MEP (27 +/- 10 cmH2O) (p < 0.001). Both MEP and MIP, which are the markers of respiratory muscle weakness, should be taken into account in the study of cough effectiveness.     

Electrical activity of the respiratory muscles in man during breath holding

Summary A study was made of the dynamics of electrical activity in the inspiratory and expiratory muscles during voluntary and involuntary breath holding in 4 persons. However it appeared on the pneumogram, voluntary apnea was biphasic. During the first phase the electrical activity was completely suppressed in both the inspiratory and expiratory muscles and action potentials were absent. In some persons investigated the second phase of voluntary apnea was attended by restoration of the rhythmic electrical activity in both the inspiratory and expiratory muscles and involuntary muscular movements appeared. Other persons, investigated during the second phase of apnea, presented disturbed rhythmic automatism of the respiratory center. Its increasing excitation was transmitted simultaneously to the inspiratory and expiratory muscles, being manifested in their static tension.In involuntary apnea, against the background of marked hypocapnia the disturbed rhythmical activity of the respiratory center continuously gave rise to intensified electrical activity in the respiratory muscles. This indicates that during involuntary apnea the respiratory center is under constant excitation.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 57, No. 4, pp. 27–33, April, 1964     

Restoration of respiratory muscle function following spinal cord injury. Review of electrical and magnetic stimulation techniques

Respiratory complications are a leading cause of morbidity and mortality in patients with spinal cord injury. Several techniques, currently available or in development, have the capacity to restore respiratory muscle function allowing these patients to live more normal lives and hopefully reduce the incidence of respiratory complications. Bilateral phrenic nerve pacing, a clinically accepted technique to restore inspiratory muscle function, allows patients with ventilator dependent tetraplegia complete freedom from mechanical ventilation. Compared to mechanical ventilation, phrenic nerve pacing provides patients with increased mobility, improved speech, improved comfort level and reduction in health care costs. The results of clinical trials of laparoscopically placed intramuscular diaphragm electrodes suggest that diaphragm pacing can also be achieved without the need for a thoracotomy and associated long hospital stay, and without manipulation of the phrenic nerve which carries a risk of phrenic nerve injury. Other clinical trials are being performed to restore inspiratory intercostal function. In patients with only unilateral phrenic nerve function who are not candidates for phrenic nerve pacing, combined intercostal and unilateral diaphragm pacing appears to provide benefits similar to that of bilateral diaphragm pacing. Clinical trials are also underway to restore expiratory muscle function. Magnetic stimulation, surface stimulation and spinal cord stimulation of the expiratory muscles are promising techniques to restore an effective cough mechanism in this patient population. These techniques hold promise to reduce the incidence of respiratory tract infections, atelectasis and respiratory failure in patients with spinal cord injury and reduce the morbidity and mortality associated with these complications.     

Role of the diaphragm in trunk rotation in humans

The objectives of the present study were to test the hypothesis that the costal diaphragm contracts during ipsilateral rotation of the trunk and that such trunk rotation increases the motor output of the muscle during inspiration. Monopolar electrodes were inserted in the right costal hemidiaphragm in six subjects, and electromyographic (EMG) recordings were made during isometric rotation efforts of the trunk to the right ("ipsilateral rotation") and to the left ("contralateral rotation"). EMG activity was simultaneously recorded from the parasternal intercostal muscles on the right side. The parasternal intercostals were consistently active during ipsilateral rotation but silent during contralateral rotation. In contrast, the diaphragm was silent in the majority of rotations in either direction, and whenever diaphragm activity was recorded, it involved very few motor units. In addition, whereas parasternal inspiratory activity substantially increased during ipsilateral rotation and decreased during contralateral rotation, inspiratory activity in the diaphragm was essentially unaltered and the discharge frequency of single motor units in the muscle remained at 13-14 Hz in the different postures. It is concluded that 1) the diaphragm makes no significant contribution to trunk rotation and 2) even though the diaphragm and parasternal intercostals contract in a coordinated manner during resting breathing, the inspiratory output of the two muscles is affected differently by voluntary drive during trunk rotation.     

Synchronization of presynaptic input to motor units of tongue, inspiratory intercostal, and diaphragm muscles

The respiratory central pattern generator distributes rhythmic excitatory input to phrenic, intercostal, and hypoglossal premotor neurons. The degree to which this input shapes motor neuron activity can vary across respiratory muscles and motor neuron pools. We evaluated the extent to which respiratory drive synchronizes the activation of motor unit pairs in tongue (genioglossus, hyoglossus) and chest-wall (diaphragm, external intercostals) muscles using coherence analysis. This is a frequency domain technique, which characterizes the frequency and relative strength of neural inputs that are common to each of the recorded motor units. We also examined coherence across the two tongue muscles, as our previous work shows that, despite being antagonists, they are strongly coactivated during the inspiratory phase, suggesting that excitatory input from the premotor neurons is distributed broadly throughout the hypoglossal motoneuron pool. All motor unit pairs showed highly correlated activity in the low-frequency range (1-8 Hz), reflecting the fundamental respiratory frequency and its harmonics. Coherence of motor unit pairs recorded either within or across the tongue muscles was similar, consistent with broadly distributed premotor input to the hypoglossal motoneuron pool. Interestingly, motor units from diaphragm and external intercostal muscles showed significantly higher coherence across the 10-20-Hz bandwidth than tongue-muscle units. We propose that the lower coherence in tongue-muscle motor units over this range reflects a larger constellation of presynaptic inputs, which collectively lead to a reduction in the coherence between hypoglossal motoneurons in this frequency band. This, in turn, may reflect the relative simplicity of the respiratory drive to the diaphragm and intercostal muscles, compared with the greater diversity of functions fulfilled by muscles of the tongue.     

Experimental evaluation of the optimal tidal volume for simultaneous pacing of the diaphragm and respiratory muscles

Because of problems with pacing devices, surgical procedures, and diaphragm fatigue in pacing therapy of the phrenic nerve, we performed simultaneous pacing of the diaphragm alone and of multiple respiratory muscles in dogs and evaluated the optimal tidal volume. After intravenously anesthetizing 20 dogs with an average weight of 11kg, their tidal volume was measured with a spirometer to obtain control values. In the first 4 dogs, electrodes were sutured to the diaphragm and the optimal voltage, pulse width, and output to maximize tidal volume were determined. In the remaining 16 dogs, we stimulated individual canine respiratory muscles, i.e., the diaphragm, the rectus thoracis, and intercostal muscles 3-5 and simultaneously stimulated the diaphragm and the rectus thoracis; the diaphragm and intercostal muscles; the rectus thoracis and the intercostal muscles; or the diaphragm, rectus thoracis, and intercostal muscles. We compared a group in which a counterelectrode was positioned in each muscle group (group A) with a group in which no counterelectrode was used (group B). The best tidal volume was obtained at 10V, 50Hz, and a pulse width of 1.0ms. All the respiratory muscle pacings yielded better tidal volumes in group B than in group A. The greatest tidal volume was obtained with the rectus thoracis and intercostal muscle combination, suggesting the possibility of being able to reduce diaphragm fatigue by alternate pacing of these muscles and the diaphragm.     

Analysis of activity of motor units in the biceps brachii muscle after intercostal-musculocutaneous nerve transfer

We examined respiratory activity of motor units (MUs) in the internal intercostal nerves (IICNs)-transferred biceps brachii muscle (IC-biceps) in cats. MUs of IC-biceps showed respiratory discharges in inspiratory and expiratory phases, and these were enhanced by CO2 inhalation. Narrowing the airway also enhanced inspiratory and expiratory MUs activity. A mechanical load to the thorax immediately enhanced inspiratory MUs activity and weakened expiratory MUs activity. We analyzed the cross-correlation of MUs activity in interchondral muscle and IC-biceps to characterize the respiratory spinal descending inputs to motoneurons. We confirmed the short-term synchronization from interchondral muscles indicating divergence of a single respiratory presynaptic axon to thoracic motoneurons, but could not find synchronization from IC-biceps. The motor axonal conduction velocity (axonal CV) of IC-biceps MUs was lower than that of interchondral muscles. There was no correlation between the respiratory recruitment order of IC-biceps MUs and their axonal CV. These results indicate that IC-biceps shows the respiratory activities and afferent inputs from intercostal muscle spindles in the neighboring segments remain influential on activity of IC-biceps. In addition, the short-term synchronization from IC-biceps could not be found, suggesting that the intercostal nerve transfer alters the respiratory spinal descending inputs to thoracic motoneurons.     

Respiratory electromyograms during resistance to breathing before and after vagal section

Summary Electrical activity of the respiratory muscles, including diaphragm, intercartilaginous part of the internal intercostal and internal oblique abdominal muscles, was recorded from electrodes chronically implanted in dogs. The disturbed coordination of the respiratory muscles which followed vagotomy was indicated by a sharp arrest of the increased electrical activity at the end of inspiration, and its failure to occur during expiration; in addition there was no longer any overlap between the activities in the inspiratory and expiratory phases. These alterations are attributed to functional changes occurring in the respiratory center and caused by the partial deafferentation through vagotomy. The functional changes in the respiratory musculature caused by introducing resistance to breathing depend on the excitation of the respiratory center, which in turn is determined by its afferentation.(Presented by Active Member AMN SSSR V. N. Chernigovskii) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 50, No. 10, pp. 34–40, October, 1960     

Activation of respiratory afferents by resistive loaded breathing modifies somatosensory evoked potentials to median nerve stimulation in humans

The cortical projections of respiratory afferents (vagus and respiratory muscle nerves) are well documented in humans. It is also shown that their activation during loaded breathing modifies the perception of tactile sensation as well as the motor drive to skeletal muscles. The effects of expiratory or inspiratory loaded breathing on somatosensory evoked potentials (SEPs) elicited by median nerve stimulation were studied in eight healthy subjects. No significant changes occurred in latencies of N20, N30 and P40 throughout the expiratory loading period, except for a significant lengthening in P1 latency compared with unloaded breathing. However, inspiratory loading induced a significant increase in peak latency of N20, N30 and P40 components. We suggest that projections of inspiratory afferents from the diaphragm and the intercostal muscles, activated by inspiratory loading, could be responsible for the lengthened latency of median nerve SEP components. Thus, respiratory afferents very likely interact with pathways of the somatosensory system.