Phrenic Activation Research Articles

Delayed poststimulus decrease of phrenic motoneuron output produced by phrenic nerve afferent stimulation.

The immediate effects of phrenic afferent nerve activation on ventilation have been shown to be both excitatory and inhibitory. Long-lasting inhibitory effects on respiratory motoneuron output have been reported after stimulation of afferent nerves from limb muscles. However, whether respiratory muscle afferent nerves can produce this effect is unknown. We therefore hypothesized that activation of phrenic afferent nerves may produce a prolonged decrease of respiratory motoneuron output. Six alpha-chloralose-anesthetized dogs were studied after vagotomy and bilateral carotid sinus nerve section. The dogs were paralyzed, and end-tidal CO2 was controlled by mechanical ventilation. The proximal end of the cut thoracic phrenic nerve was electrically stimulated for 1 min at intensities that produced activation of thin-fiber afferents. The contralateral efferent phrenic integrated electroneurogram (ENG) was recorded. During stimulation, phrenic ENG activity increased. ENG activity was recorded during recovery and reached a peak decrease compared with control of 19 +/- 11% (SD) 9.0 +/- 6 min after stimulation and returned to control after 30 min. A qualitatively similar response was seen after stimulation of the gastrocnemius nerve. We conclude that activation of thin-fiber afferents in the phrenic nerve can produce a delayed and prolonged decrease of respiratory motoneuron output similar to that of limb muscle afferent nerves.

Effect of phrenic afferent stimulation on pattern of respiratory muscle activation.

Ventilation and electromyogram (EMG) activities of the right hemidiaphragm, parasternal intercostal, triangularis sterni, transversus abdominis, genioglossus, and alae nasi muscles were measured before and during central stimulation of the left thoracic phrenic nerve in 10 alpha-chloralose anesthetized vagotomized dogs. Pressure in the carotid sinuses was fixed to maintain baroreflex activity constant. The nerve was stimulated for 1 min with a frequency of 40 Hz and stimulus duration of 1 ms at voltages of 5, 10, 20, and 30 times twitch threshold (TT). At five times TT, no change in ventilation or EMG activity occurred. At 10 times TT, neither tidal volume nor breathing frequency increased sufficiently to reach statistical significance, although the change in their product (minute ventilation) was significant (P less than 0.05). At 20 and 30 times TT, increases in both breathing frequency and tidal volume were significant. At these stimulus intensities, the increases in ventilation were accompanied by approximately equal increases in the activity of the diaphragm, parasternal, and alae nasi muscles. The increase in genioglossus activity was much greater than that of the other inspiratory muscles. Phrenic nerve stimulation also elicited inhomogeneous activation of the expiratory muscles. The transversus abdominis activity increased significantly at intensities from 10 to 30 times TT, whereas the activity of the triangularis sterni remained unchanged. The high stimulation intensities required suggest that the activation of afferent fiber groups III and IV is involved in the response. We conclude that thin-fiber phrenic afferent activation exerts a nonuniform effect on the upper airway, rib cage, and abdominal muscles and may play a role in the control of respiratory muscle recruitment.

Effect of abdominal compression on diaphragmatic tendon organ activity.

Previous studies suggest that afferents in the diaphragm participate in the reflex reduction in phrenic nerve efferent activation when the length of the diaphragm is increased by abdominal compression. The present study determined the response of tendon organ afferents in the diaphragm to increases in abdominal pressure. Five cats were anesthetized with thiopental sodium (60 mg/kg ip to induce, supplemented intravenously). Extracellular recordings from nine individual tendon organ afferents were made from right cervical dorsal root ganglia 5 and 6. Right crural electromyographic activity was recorded. The right extrathoracic phrenic nerve was isolated and stimulated to identify tendon organs on the basis of conduction velocity and response to twitch. The response to ramp-and-hold stretch of the diaphragm was used as an additional test to differentiate tendon organs from muscle spindles. The mean level of activity of the tendon organs during the 1st s of the inspiratory phase was 47 +/- 10 (SD) Hz. Abdominal compression was associated with a significant increase in the activity of these afferents to 61 +/- 11 Hz. Results indicate that increases in the activity of diaphragmatic tendon organs are associated with moderate increases in abdominal pressure and are likely the result of elevations in the active tension developed by the diaphragm. Combined with results from previous studies, it is possible that diaphragmatic tendon organs may play a role in the attenuation of respiratory muscle activation when abdominal pressure is increased.

Reflex modulation of phrenic activity through hindlimb passive motion in decorticate and spinal rabbit preparation

The neurogenic effect of passive hindlimb movement on phrenic nerve discharge was compared in decorticate unanaesthetized and curarized rabbit preparations prior to and after spinal transection. The question of how and where sensory information has access to the central respiratory network was addressed in each case. All passive motions, performed using a mechanical device, were of constant amplitude in a given preparation. The results clearly differed in decorticate and spinal preparations. In the decorticate vagotomized preparation, periodic passive motions led to an immediate shortening of the respiratory period which lasted throughout the periodic stimulation and stopped with its cessation; it did not depend on the frequency of the natural stimulation and was entirely due to a 20% shortening of the expiration time. Maintained full flexion or full extension both induced the same expiration time shortening, but limited to the first two to three respiratory cycles after onset and interruption of stimulation. After spinal transection at the C2 level and moderate activation with DOPA, no phrenic activity developed in the absence of proprioceptive stimulation. Periodic hindlimb movements evoked simultaneous large bursts in both phrenic nerves during each extension; a 1:1 coordination of phrenic activity with the external imposed period ( P) was observed for various P values. A strong phrenic activation could also be elicited through maintained full hindlimb extension but not through full flexion: this activation appeared as rhythmic discharge as long as extension was maintained. It is concluded that proprioceptive inputs act upon the medullary respiration generator and reset its own rhythm whereas, at the spinal level, they elicit an amplitude modulation at phrenic motoneuronal level without acting upon the rate of the spinal “respiration” generator itself; on the same phrenic motoneurons, a subthreshold central activation added to a subthreshold proprioceptive activation probably accounts for the phrenic bursting during maintained extension. Finally, the proprioceptive control from the hindlimb on phrenic activity is processed at different sites of the central respiratory network at medullary and at spinal level and may depend on different input signals.

Ventilatory effects of stimulation of phrenic afferents.

The diaphragm, a ventilatory muscle, has abundant sensory innervation. The effects of phrenic afferent activation on ventilation have been varied. In this study the proximal end of the phrenic nerve was electrically stimulated, and the effects on ventilation were measured in supine dogs anesthetized with either alpha-chloralose or pentobarbital sodium. We found a maximum increase in ventilation of 45 +/- 4% in the alpha-chloralose group and an increase in mean arterial blood pressure of 18 +/- 4%. This response was obtained at high stimulus intensities (60 times twitch threshold). Stimulation of the proximal end of the gastrocnemius nerve produced a similar ventilatory response (61 +/- 10%) but at lower stimulus intensities. During pentobarbital sodium anesthesia both the hyperventilation and the pressor response were produced; however, ventilation was increased by an increase in respiratory frequency. The reflex was abolished by sectioning of the cervical dorsal roots (C4-C7). Proximal cold blockade of the nerve abolished the response at a perineural temperature of 1.35 +/- 0.64 degrees C. The main effect of activation of phrenic afferents was an increase in ventilation and blood pressure that was mediated by unmyelinated fibers and possibly thin myelinated fibers. This response is similar to skeletal muscle afferent activation and may play a role in ventilatory drive during such conditions as exercise and respiratory muscle fatigue.

Comparison of phrenic motoneuron activity during eupnea and gasping.

Single-fiber phrenic nerve action potentials were recorded together with activity of contralateral whole phrenic nerve rootlets during eupnea and gasping in decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats. Gasping was reversibly produced by cooling a fork thermode positioned through the pontomedullary junction. In eupnea, phrenic motoneurons were distributed into "early" and "late" populations relative to their onset of activity during inspiration. During gasping, however, both fiber types typically commenced activity at the beginning of the phrenic nerve burst. Moreover, late fibers, but not early units, exhibited an augmentation of discharge frequency with the onset of gasping. The concentration of activity of all phrenic motoneurons at the beginning of inspiration and the increase in late-unit discharge frequency account for the faster rise of the gasp as compared with the eupneic breath. It is concluded that the pattern of phrenic nerve activation during gasping differs fundamentally from that during eupnea. These results support the concept that mechanisms underlying the neurogenesis of gasping and eupnea may not be identical.

Function of the isolated paced diaphragm and the cervical accessory muscles in C1 quadriplegics.

Function studies of the electrically paced diaphragm and of the sternomastoid and trapezius muscles acting alone were carried out in 3 young C1 quadriplegic men. Phrenic pacing offers the unique advantages of allowing one to examine the function of the diaphragm acting alone, keeping the degree of phrenic activation constant while examining its mechanical responses to other variables. Changes in anteroposterior and lateral diameters of both rib cage and abdomen were measured with magnetometers; changes in pressure and volume were recorded together with thoracoabdominal motion as indices of inspiratory muscle effectiveness as lung volume and body position were changed. Isolated paced diaphragmatic contraction caused both abdominal diameters and the lateral diameter of the lower rib cage to increase. The anteroposterior and lateral diameters of the upper rib cage, however, decreased. Isolated contraction of the trapezii and sternocleidomastoids caused decreases in all diameters except for the anteroposterio...

Coordinated rhythmic bursting in respiratory and locomotor muscle nerves in the spinal rabbit

In unanaesthetized, curarized spinal rabbits (C2 level) treated with Niamide and DOPA, rhythmic activities were recorded from the phrenic nerves; close coordination was observed between the phrenic bursts and the locomotor bursts which developed in hindlimb muscle nerves. The frequency of phrenic bursts was reduced after a second spinal transection at the Th12 level, while rhythms in the hindlimb remained unchanged. It thus appears that in the spinal preparation and under certain pharmacological conditions, phrenic bursts generated by the cervico-thoracic spinal cord can be driven by the lumbar generators of locomotion; spinal links thus exist between these hindlimb locomotion generators and spinal interneuronal networks involved in phrenic motoneuronal activation, may be via hindlimb forelimb driving.