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[The structure of muscle spindles in the intercostal muscles and rectus abdominis of the human fetus].

The structure and innervation of muscle fibres were studied in external intercostal muscles and the streight muscle of the abdomen in 24--26-week human fetuses. The diameter of most spindles was shown to be within the range of 50--70 mkm, while in the streight muscle of the abdomen it could reach 100 mkm. In the external intercostal muscles the spindles, as a rule, were longer (300-500 mkm) than in the streight muscle of the abdomen (100--300 mkm) which was likely due to special functioning of the spindles in rhythmically working muscles. According to sensory innervation all the spindles may be divided into 3 main types: simple, intermediate and complex. In the external intercostal muscles there occur 3 types of spindles, while in the streight muscle of the abdomen there are spindles of a complex type.

Humans

Intercostal muscles are used during rotation of the thorax in humans.

To test the idea that the lateral intercostal muscles may be more suited to aid in rotational than respiratory movements of the thorax, we inserted bipolar fine-wire electrodes in external and internal intercostal muscles in the right midaxillary line in nine sitting subjects and examined the pattern of contraction of these muscles during voluntary axial rotations of the thorax (30-35 degrees), resting breathing, and CO2-induced hyperpnea. The right external intercostal muscles were strongly recruited in rotations to the left but were not active in rotations to the right. In contrast, the right internal intercostal muscles were active in rotations to the right but not in rotations to the left. Rotations completed in 1 or 2 s were associated with an early burst of electromyographic activity, followed by a low plateau that persisted while the rotation was held. Rotations made very gradually over 5-10 s were associated with gradually rising electromyographic activity. The amplitude of activity recorded during 30-35 degrees rotations was equivalent to that measured when minute ventilation was increased by CO2 to 50 l/min. We conclude that the lateral intercostal muscles have a major role in producing axial rotations of the thorax.

Adult

Intercostal muscle action inferred from finite-element analysis.

The external and internal intercostal muscles are important respiratory muscles in humans, but their mechanical actions have been controversial. We used finite-element analysis based on anatomic and mechanical measurements in dogs to assess the action of the intercostal and other rib cage muscles in a model of an isolated canine rib cage. When intercostal muscle forces of either the internal or the external layer were applied in a single interspace, they pulled the adjacent ribs together, consistent with published observations in dogs. However, when the forces were applied in all interspaces, the external layer caused an inspiratory motion and the internal layer caused an expiratory motion, consistent with conventional understanding of intercostal muscle actions. Parasternal intercostal, levator costae, and transversus thoracis (triangularis sterni) muscle actions were also simulated. These muscles caused expected movements of the ribs and sternum. We conclude that the actions of intercostal muscles depend on the spatial extent of their activation. Their actions in a single interspace and in multiple interspaces can be observed and explained with three-dimensional finite-element models.

Animals

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

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.

Animals

The electro-mechanical response of canine inspiratory intercostal muscles to increased resistance: the cranial rib-cage.

1. The effect of graded increases in inspiratory airflow resistance on the electrical activity and the mechanical behaviour of the three groups of inspiratory intercostal muscles (parasternal intercostal, external intercostal, levator costae) situated in the cranial portion of the rib-cage has been studied in ten anaesthetized, spontaneously breathing dogs. The mechanical behaviour of the muscles was determined by measuring the respiratory changes in muscle length and the displacements of the rib. 2. During unloaded inspiration, the three muscles were active, the rib moved in the cranial direction, and the parasternal intercostal and levator costae muscles shortened; in most animals, the external intercostals shortened as well. 3. Graded increases in inspiratory airflow resistance elicited a progressive inhibition of parasternal intercostal activity and a gradual facilitation of external intercostal and levator costae activities. Concomitantly, the parasternal intercostals continued to shorten during inspiration. However, both the external intercostals and the levator costae progressively lengthened, and the rib was gradually displaced in the caudal direction. This pattern persisted after increases in chemical respiratory drive had developed. 4. Sectioning the phrenic nerve roots did not alter the electrical or the mechanical response of the parasternal intercostal muscles to loading, but it markedly affected the response of the external intercostals and levator costae. After phrenicotomy, the external intercostals and levator costae continued to shorten during loaded breaths, the rib continued to be displaced in the cranial direction, and although the rate of inspiratory muscle shortening and of rib motion decreased, the facilitation of external intercostal and levator costae activities was markedly reduced or abolished. 5. Lengthening of the external intercostals and caudal displacement of the rib was reproduced by isolated stimulation of the phrenic nerves. 6. The reflex facilitation of external intercostal and levator costae activities that takes place during inspiratory resistive loading thus results primarily from the collapsing action of the diaphragm on the cranial portion of the rib-cage and the consequent lengthening of these muscles. The mechanical effectiveness of this reflex facilitation, however, appears to be relatively small.

Airway Obstruction

Action of intercostal muscles on the lung in dogs.

The action on the lung of interosseous intercostal muscles located in the third and the seventh interspaces was studied in 15 anesthetized-curarized supine dogs. Changes in pleural pressure, airflow rate, and lung volume produced by maximal stimulation of both intercostal muscle layers were measured at and above functional residual capacity (FRC). In five animals measurements were also obtained during isolated stimulation of the internal layer. At FRC, intercostal stimulation in the upper interspaces had invariably an inspiratory effect on the lung but no effect was detectable in the lower interspaces. Qualitatively similar results were obtained during isolated stimulation of the internal layer. Increasing lung volume reduced the inspiratory action of the upper intercostals and conferred an expiratory action to the lower intercostals. These results indicate the following: 1) when contracting in a single interspace, the external and internal intercostals have a qualitatively similar action on the lung; and 2) this action, however, depends critically on their location along the cephalocaudal axis of the rib cage: in the upper portion of the rib cage, both muscle layers have an inspiratory effect at and above FRC; in the lower portion of the rib cage, they have no respiratory action at FRC and act in the expiratory direction at higher lung volumes.

Animals

Comparative electrophysiology and pharmacology of mammalian (including one marsupial) intercostal muscle biopsy preparations.

Characteristics of minature end-plate potentials (MEPP) of isolated external intercostal muscle preparations of 7 mammalian species (dog, cat, pig, horse, cow, and goat) including 1 marsupial (opossum, Didelphis marsupialis) were determined with intracellular microelectrodes. Mean amplitude (+/- standard error of MEPP for all species was 0.60 +/- 0.06 mV, and the range was 0.28 mV (opossum) to 1.07 mV (pig). Amplitude was inversely correlated (P less than 0.01) with muscle fiber diameter which ranged from 93 mum (opossum) to 51 mum (pig). Mean values for rise time, half-decay time, and frequency of MEPP for all species were 0.88 +/- 0.07 msec, 1.89 +/- 0.16 msec, and 0.44 +/- 0.12 MEPP/second, respectively. Species differences among these measurements were not statistically significant. Resting potentials ranged from 64 mV (pig) to 75 mV (cow and opossum). Amplitude of MEPP was reduced significantly by d-turbocurarine (0.06 muM) only in preparations from the dog (P less than 0.01), pig (P less than 0.05), cow (P less than 0.01), and goat (P less than 0.01), suggesting species variations in sensitivity to this neuromuscular blocking agent. Frequency of MEPP decreased in the prescence of d-tubocurarine, but the change was not significant. The techniques utilized in this study and the results obtained will have application in evaluation of intercostal muscle biopsy preparations from these species when affected by myasthenic diseases.

Action Potentials

Hyperthyroid myopathy. Intracellular electrophysiological measurements in biopsied human intercostal muscle.

Morphological and electrophysiological studies were performed on intercostal muscle biopsies from 2 thyrotoxic patients. The diseased fibers had numerous areas of subsarcolemmal glyogen accumulations and abnormal membranous projections. Both Type I and Type II muscle fibers were atrophied. Diseased fibers were substantially depolarized and when artifically hyperpolarized showed earlier inactivation of the sodium conductance as a function of membrane potential, and a critical depolarization potential more depolarized than in normal fibers. When stimulated at 20 pulses/sec, or faster, the diseased fibers could not generate normal action potentials due to membrane depolarization and the appearance of a marked after-hyperpolarization. Muscle weakness associated with hyperthyroidism is attributed to the reduced membrane excitability.

Adult

Differential control of the inspiratory intercostal muscles during airway occlusion in the dog.

1. The effect of airway occlusion on the electrical activity of the three groups of inspiratory intercostal muscles (external intercostal, levator costae, parasternal intercostal) situated in the cranial portion of the rib-cage has been studied in thirty anaesthetized, spontaneously breathing dogs. 2. The three muscles were active during normal inspiration, and their activity was prolonged similarly during airway occlusion. However, a comparison of activity during occluded and unoccluded inspirations indicated that airway occlusion caused a facilitation of external intercostal and levator costae activities but an inhibition of parasternal intercostal activity. 3. The facilitation of external intercostal and levator costae activities was markedly reduced after section of the phrenic nerves and completely suppressed after section of the appropriate thoracic dorsal roots. 4. The inhibition of parasternal intercostal activity was not affected by section of the phrenic nerves or by section of the thoracic dorsal roots. This phenomenon, however, was abolished after bilateral cervical vagotomy. 5. Activation of the external intercostals and levator costae during inspiratory efforts are thus highly dependent on segmental reflexes arising in these muscles. In contrast, activation of the parasternal intercostals resembles that of the diaphragm in the sense that it depends primarily on the central respiratory drive.

Airway Obstruction

The electro-mechanical response of canine inspiratory intercostal muscles to increased resistance: the caudal rib-cage.

1. The effect of graded increases in inspiratory airflow resistance and airway occlusion on the electrical activity and the mechanical behaviour of the levator costae and external intercostal muscles situated in the caudal interspaces (zone of apposition of the diaphragm to the rib-cage) has been studied in spontaneously breathing dogs. 2. The external intercostal and levator costae muscles in the cranial interspaces were invariably active during unloaded inspiration and showed progressive facilitation of activity with increases in inspiratory resistance. In contrast, whether in the supine or in the prone position, the levator costae muscles of the caudal interspaces did not show any facilitation of activity, and the caudal external intercostal muscles never showed any inspiratory electrical activity, including during airway occlusion. 3. With graded increases in inspiratory airflow resistance, the cranial external intercostals demonstrated a gradual inspiratory lengthening and the cranial ribs were progressively displaced in the caudal direction. The caudal ribs, however, were invariably displaced in the cranial direction. As a result, the caudal external intercostals showed a progressive inspiratory shortening. 4. Shortening of the caudal external intercostals and cranial displacement of the caudal ribs were reproduced by isolated stimulation of the phrenic nerves. Thus, as inspiratory resistance increases, contraction of the diaphragm causes unloading, rather than loading, of the spindles present in the caudal external intercostal muscles. 5. After the phrenic nerves were sectioned, however, the caudal external intercostals invariably lengthened a substantial amount during inspiration, but they still did not show any inspiratory electrical activity. Accentuating the inspiratory lengthening of these muscles by external rib fixation and increasing the chemical respiratory drive did not elicit any inspiratory electrical activity either. The alpha-motoneurones of the external intercostal muscles in the caudal interspaces thus have very small central respiratory drive potentials with respect to their critical firing threshold.

Airway Obstruction

Rostrocaudal variation of fiber type composition in rat intercostal muscles.

We used the histochemical stain for ATPase to compare the fiber-type composition of rat internal and external intercostal muscles from thoracic (T) segments 2-5, 8, and 11. At each level, type II fibers were more numerous than type I fibers, type II B fibers were more numerous than II A fibers, and type I fibers were more numerous in external than in internal intercostals. However, fiber type composition varied from segment to segment. For example, the proportion of type II A fibers increased in a rostrocaudal gradient in internal but not external intercostals, and type I fibers were more prevalent at rostral and caudal than at intermediate levels in both internal and external intercostals. These results provide a basis for interpreting previous physiological and molecular studies which have compared intercostal muscles from different segmental levels.

Adenosine Triphosphatases

Intercostal muscle biopsy in human neuromuscular disease. Histochemical and electron microscopic studies.

External intercostal muscle biopsies were examined histochemically and by electron microscopy. The use of this muscle allowed correlation with physiological and pharmacological studies on the same specimens. Changes observed in musclar dystrophy and motor neurone disease resembled those previously described in biopsied limb muscle and underline the particular usefulness of this preparation in the study of human neuromuscular disease.

Adenosine Triphosphatases

Spike trains from single motor units in human parasternal intercostal muscles.

Recordings of single motor unit activity were obtained from parasternal intercostal muscles of normal humans during quiet breathing. Spike trains from 52 individual motor units were analyzed. All these units were low threshold ones, recruited at low inspired volumes and therefore at low tension thresholds. Mean frequency of firing at onset was 7.8 Hz and mean increase in frequency through the breath was 3.6 Hz. Onset and peak frequencies were positively correlated with inspiratory flow rate. Alternation of interspike intervals between long and short was found in the spike trains of 6 of 13 units tested and this occurred at frequencies of 6-12/s. Doublet discharges at the beginnings of spike trains were seen during voluntary neck flexion but never in quiet breathing or voluntary deep breaths. The pattern of activity in these human intercostal motor units was similar to that reported for low threshold, slow twitch units in other mammalian skeletal muscles, including respiratory muscles.

Action Potentials

Na+ current densities and voltage dependence in human intercostal muscle fibres.

1. Voltage-clamp Na+ currents (INa) were studied in human intercostal muscle fibres using the loose-patch-clamp technique. 2. The fibres could be divided into two groups based upon the properties of INa. The two groups of fibres were called type 1 and type 2. 3. Both type 1 and type 2 fibres demonstrated fast and slow inactivation of INa. 4. Type 1 fibres had lower INa on the endplate border and extrajunctional membrane than type 2 fibres and required larger membrane depolarizations to inactivate Na+ channels by fast or slow inactivation of INa. 5. Type 2 fibres had a higher ratio of INa at the endplate border compared to extrajunctional membrane than Type 1 fibres. 6. Measurement of membrane capacitance suggested that the increase in INa at the endplate border was due to increased Na+ channel density. 7. Histochemical staining of some fibres suggested that type 1 fibres were slow twitch and type 2 fibres were fast twitch. 8. Differences in the properties of Na+ channels between fast- and slow-twitch fibres may contribute to the ability of fast-twitch fibres to operate at high firing frequencies and slow-twitch fibres to be tonically active.

Electric Stimulation

The response to stretch of human intercostal muscle spindles studied in vitro.

1. The discharge properties of human muscle spindles have been studied in vitro in a preparation based on the biopsied external intercostal muscle. 2. The static and dynamic responsiveness of thirty-six endings in twenty visualized and histologically identified spindles have been investigated using amplitudes and velocities of stretch likely to encompass those occurring in vivo. 3. The dynamic index, measured at a stretch velocity of 3 mm/sec, ranged from 3 to 40 impulses/sec and was distributed bimodally, consitent with the presence of primary and secondary endings. 4. The relationship between the dynamic index and the velocity of stretch was approximately linear both for primary and secondary endings up to the maximum velocity tested (10 mm/sec). 5. The frequency/extension relationship was approximately linear for both primary and secondary endings. The mean values of the slope for primary and secondary endings were 16-1 +/- 8-3 S.D. of the observation and 12-1 +/- 6-5 impulses/sec per five per cent extension. 6. The slopes of the frequency/extension relationship for endings lying in the same spindle were positively correlated, significant at the 10% level. 7. It was estimated from the results in vitro that the position sensitivity of human intercostal spindles in vivo ranges from 2 to 21 impulses/sec per millimetre.

Action Potentials

Electrophysiologic properties of intercostal muscle fibers in human neuromuscular diseases.

Electrophysiologic properties of biopsied normal and diseased intercostal muscle fibers were examined using intracellular microelectrode techniques. The resting potentials of all diseased muscle fibers were found to be depolarized. Those from Duchenne dystrophy patients showed the largest depolarization, followed by those from patients with myotonic muscular dystrophy, myotonia congenita, and motor neuron disease. All of the diseased fibers except those from myotonia congenita patients demonstrated an imparied ability to generate action potentials. In the latter fibers, the higher-than-normal membrane resistance was associated with hyperexcitability. When the membrane was hyperpolarized to the normal range, however, action potential characteristics in all fibers were near normal, except in motor neuron disease. All action potentials were blocked by tetrodotoxin. These findings--i.e., that all fibers were capable of generating action potentials when hyperpolarized, and that all action potentials were blocked by tetrodotoxin--suggest the relative intactness, in the disease studied here of the regenerative sodium conductance mechanism.

Action Potentials

Relationship between parasternal and external intercostal muscle length and load compensatory responses in dogs.

1. The effects of tracheal occlusion on peak parasternal (PA) and external intercostal (EI) (3rd interspace) EMG activities were examined at different end-expiratory lung volumes both above and below functional reserve capacity (FCR) in anaesthetized, vagotomized and spontaneously breathing dogs. 2. Parasternal (PA) and external intercostal (EI) muscle lengths were monitored in situ. The difference in peak EMG activity between free and occluded breaths (test breaths) was related to the coincident peak change in intercostal muscle length (delta L) for each muscle, respectively. 3. At FRC, tracheal occlusion resulted in compensatory augmentation of peak EI, but little change in peak PA EMG activities. At lung volumes below FRC, airway occlusion resulted in augmentation of both PA and EI activities. Responses to airway occlusion at lung volumes above FRC were variable. The magnitude and duration of these changes in EMG, however, could be linearly related to the value of delta L. With delta L = 0, there was no change in peak EI or PA EMG; for values of delta L less than 0, there was attenuation of EI and PA EMG; for delta L greater than 0, there was enhancement of EI and PA EMG activation. 4. The magnitude of the changes in EMG activity in response to tracheal occlusion was more prominent for the EI muscle compared to the PA, the latter of which are known to have much fewer muscle spindles than EI muscle. 5. Our results suggest that a difference in end-inspiratory muscle length between the control and occluded breaths is a stimulus for the intercostal response to applied loads implicating muscle spindles as the predominant receptor moderating these responses. We hypothesize that when delta L = 0, no change in EMG occurs since the spindles sense no change in muscle length. When delta L less than 0 (i.e. peak muscle length during the occluded breath is shorter than control) muscle spindles would be disengaged, resulting in a disfacilitation of EMG activity. Where delta L greater than 0 (i.e. peak muscle length during the occluded breath is longer than control), muscle spindles are stimulated, resulting in enhancement of EMG activity. 6. Additional doses of Nembutal (20 mg), which produced significant changes in breathing pattern, did not affect the magnitude of the load compensatory responses.

Animals