Bilateral reflex effects on phrenic nerve activity in response to single-shock vagal stimulation

The bilateral reflex actions of vagus nerve afferent signals on phrenic efferent activity have been tested by unilateral graded single shock electrical stimulation. An early excitation (latency 3–5 msec) was more prominent in the phrenic nerve contralateral to the stimulated vagus. Spinal cord hemisection at C₃ eliminated both contralateral and ipsilateral responses: thus, both were mediated via descending tracts in the contralateral cord. A bilaterally symmetrical early inhibition (latency 8–12 msec) followed the early excitation. The electrical thresholds for evoking the early responses and the temperature for blocking these responses during graded vagal cooling were closely similar to the threshold and blocking temperature for pulmonary stretch receptor afferents. Higher stimulus strengths evoked a strong, bilaterally similar, late excitation (latency 12–20 msec) followed by a late inhibition. At very high stimulus strengths a third excitation (latency 25–30 msec) could appear. Sometimes these responses were followed by lowered phrenic activity for the remainder of inspiration. Single shock stimulation of the intact vagus nerve or of the peripheral end of the cut recurrent laryngeal nerve provoked. by the contraction of laryngeal muscles, a strong, short latency (12 msec) inhibition of phrenic activity mediated by superior laryngeal nerve afferents. The implications of these results with respect to the reflex pathways of the different responses and their possible integration in the central respiratory control mechanisms are discussed.     

Morphology and electrophysiology of superior laryngeal nerve afferents and postsynaptic neurons in the medulla oblongata of the cat.

Intra-axonal recordings were made from 24 afferent fibres of the superior laryngeal nerve in and around the nucleus tractus solitarius, in 26 pentobarbitone-anaesthetized cats. Conduction velocity ranged from 15 to 38 m/s. Four afferents were injected with horseradish peroxidase. They showed dense terminal arborization in the region of the ventral and ventrolateral subnuclei of the nucleus tractus solitarius, both rostral and caudal to the obex. Six other intra-axonal recordings were thought to originate from axons of neurons postsynaptic to superior laryngeal afferents; one of these was injected with horseradish peroxidase and showed a similar arborization pattern to that of the afferent axons. In the same region, intracellular recordings were made from 124 neurons which responded to superior laryngeal nerve stimulation with excitatory postsynaptic potentials (mean latency 2.7 +/- 1.0 ms). Ninety-nine of these neurons were thought to receive a monosynaptic input. The stimulation threshold evoking these responses was similar to that which inhibited phrenic nerve discharge. Eleven of the monosynaptically excited neurons were injected with horseradish peroxidase. They had fusiform or stellate somata and simple dendritic trees, radiating mainly in the transverse plane. In one experiment, in which both a superior laryngeal nerve afferent fibre and a neuron were labelled, afferent terminal varicosities were found in close apposition with the postsynaptic membrane of the injected neuron. Four of 14 (29%) tested neurons could be antidromically activated from the C3 spinal segment. The stimulus thresholds and onset latencies of the responses of superior laryngeal nerve afferents and medullary neurons to stimulation of the superior laryngeal nerve are consistent with their involvement in the reflex inhibition of respiratory neurons evoked by superior laryngeal nerve stimulation.     

Extra-segmental reflexes derived from intercostal afferents: phrenic and laryngeal responses

1. Phrenic and recurrent laryngeal efferent responses were evoked by brief tetani or single shocks to the cut external intercostal nerves of anaesthetized cats. The reflexes derived from middle thoracic segments (T5 and 6) were compared with those emanating from caudal thoracic segments (T9 and 10).2. During inspiration, middle intercostal nerve stimulation transiently inhibited the spontaneous discharge in both efferent neurograms, whereas stimulation of caudal intercostal nerves facilitated phrenic discharge and usually inhibited recurrent laryngeal activity.3. During expiration, stimulation at either thoracic level enhanced recurrent laryngeal discharge while provoking little or no phrenic response.4. Superficial lesions of the lateral cervical cord, ipsilateral to the stimulus sites, above or below the phrenic outflow, eliminated all reflex responses except the phrenic response to caudal thoracic stimuli. Similarly, in the spinal animal, middle intercostal afferents could not be shown to decrease phrenic excitability. Caudal intercostal afferents cause phrenic excitation by a spinal reflex.5. Group I afferents of the mid-thoracic segments and group II afferents of the caudal thoracic segments initiate these extra-segmental reflexes.6. The recurrent laryngeal responses manifest, for the most part, changes in the discharge of fibres innervating the posterior cricoarytenoid muscle. The responses fit the overall pattern of response to middle intercostal nerve stimulation, namely, inhibition of inspiratory muscles and excitation of expiratory muscles. Intercostal afferent stimulation also activated the laryngeal adductor muscles.7. The results support the view that intercostal mechanoreceptors initiate an array of extra-segmental respiratory reflexes, including spinal and supraspinal arcs. The simplest way to account for the various responses to stimulation of middle intercostal afferents is to postulate a reflex involving supraspinal respiratory neurones.8. The observed reflexogenic differences correlate with anatomical differences between the middle and caudal ribs. Possible functional implications of this relationship are discussed.     

Presynaptic depolarization in myelinated vagal afferent fibres terminating in the nucleus of the tractus solitarius in the cat

The presynaptic influences that act on terminals of slowly adapting lung stretch receptor afferents and aortic baroreceptor afferents within the nucleus of the solitary tract were assessed using intracellular recording and antidromic stimulation techniques.Central respiratory influences on the axcitability of lung stretch receptor terminals were observed in 29% (4 of 14) of measurements. These were confirmed in intracellular recordings where membrane depolarizations in synchrony with phrenic nerve discharge were seen in 17% (4 of 24) of fibres. In three cases membrane depolarization also occurred synchronously with artificial lung inflation.Neither tests of excitability nor intracellular recording revealed any evidence for equivalent presynaptic influences on 16 myelinated aortic baroreceptor terminals.Stimulation of the superior laryngeal nerve evoked depolarizations in 50% (7 of 14) of lung stretch receptor terminals. These took the form of complex waves of depolarization with both short (3–8 ms) and long latency (27–35 ms) components. The amplitude of the long latency response increased during the period of phrenic nerve discharge, i.e. during central inspiration.These effects are discussed in relation to the central respiratory influences on both respiratory and cardiovascular reflexes.     

Responses of ventral respiratory neurones in the rat to vagus stimulation and the functional division of expiration.

In anaesthetized rats, extracellular and intracellular recordings were taken from 106 respiratory neurones in the intermediate region of the nucleus ambiguus. We observed unprovoked shortening of expiratory time accompanied, in all classes of respiratory neurone, by the elimination of the changes in membrane potential that were characteristic of stage II expiration. The demonstration of the elimination of stage II expiration in both the rat and cat strongly supports the functional division of expiration into stage I expiration (post-inspiration) and stage II expiration. In order to identify the neurones in the rat that receive inputs from vagal afferents and modulate the central respiratory rhythm, we examined whether any respiratory neurones responded to stimulation of the vagus nerve. Some post-inspiratory and stage II expiratory neurones responded. The short latency (< 2 ms) of four of the responses indicates that some vagal afferents act on post-inspiratory neurones via a disynaptic pathway. While repetitive stimulation of the vagus nerve could inhibit the phrenic rhythm, it appears that most inspiratory neurones in the intermediate region of the nucleus ambiguous complex are not directly involved in integrating the information from vagal afferents with the central respiratory rhythm.     

Inspiratory on-switch evoked by stimulation of the mesencephalon: Activity of phrenic and laryngeal motoneurones

Summary In anaesthetized cats (chloralose-urethan) the effects of brief tetanic electrical stimulation (50 to 100 ms) of the mesencephalic central gray matter and reticular formation on the inspiratory on-switch were studied during the expiratory (E) phase on the gross and unitary activities of phrenic, laryngeal inspiratory and laryngeal expiratory nerves. On the inspiratory laryngeal and phrenic nerves, stimulation elicited a short latency gross response concomitant with the train: the inspiratory Primary Response (Prim.R.) which is followed by an inspiratory Patterned Response (Patt.R.) of longer duration which corresponded to the inspiratory on-switch. The Patt.R. generally appeared from the Prim.R. within a latent period (Silent Phase: Sil.P.) as long as 100 ms. On the expiratory laryngeal nerve, stimulation elicited a brief activation (expiratory Prim.R.) concomitant with the beginning of the inspiratory laryngeal Prim.R. and which rapidly stopped as the latter continued during the stimulus train. The inspiratory Prim.R. corresponded to a simultaneous activation of both early and late (so defined during their spontaneous discharge) inspiratory motoneurones. The laryngeal motoneurones were more strongly activated than the phrenic ones. During the inspiratory Patt.R. all the phrenic motoneurones presented a recruitment delay earlier, compared with the spontaneous one, whereas the recruitment drastically changed from an inspiratory laryngeal motoneurone to another. Thus, the two pools of motoneurones presented different properties of activation. During the inspiratory Sil.P. no concomitant expiratory laryngeal activation was observed when most of the inspiratory motoneurones were inactive. As some inspiratory laryngeal motoneurones did not stop firing, the existence of some central respiratory neurones exhibiting a similar persistent activity and subserving the inspiratory on-switch mechanisms may be hypothesized.Supported by CNRS (LA 205 and ATP n 4188) and Fondation pour la Recherche Médicale     

Effects of stimulation of phrenic afferent fibers on medullary respiratory neurons in cat

The effects of electrical stimulation of both cervical branches (C5 and C6) of the right phrenic nerve on medullary respiratory neuron activity were studied in anesthetized, spontaneously breathing cats. In 14 cats, the stimulation of the thin phrenic afferents had no effect on the inspiratory duration and evoked excitatory or inhibitory responses in only 3/86 inspiratory neurons tested. In 3 cats, the stimulation decreased the inspiratory duration and 26/26 inspiratory neurons showed a shortened discharge without modification of their discharge frequency. Although the effects of the stimulation were not analysed by averaging techniques, it is concluded that phrenic afferents do not exert an important control on the medullary respiratory neuron discharge.     

Pharyngeal motoneurones: respiratory-related activity and responses to laryngeal afferents in the decerebrate cat

Summary In decerebrate, paralyzed and artificially ventilated cats, we recorded the discharge of 64 motor axons supplying the pharyngeal muscles. Filaments containing motor axons, with discharges related to the respiratory cycle (phrenic nerve activity), were teased from the pharyngeal branches of the vagus and glossopharyngeal nerves. Most units (n = 41) fired only during expiration and exhibited a steady, a decreasing or a late augmenting discharge pattern. These units were found only in vagal filaments. Twenty three units discharged during inspiration and exhibited a steady, a late augmenting or a tonic discharge pattern. The inspiratory-related units were present in both the vagus (n=13) and glossopharyngeal (n=10) nerves. Nineteen of 20 pharyngeal inspiratoryrelated units tested were activated at short latency (range 3.4 to 8.0 ms) by stimulation of afferents in the superior laryngeal nerve (SLN). In 13 of these, such stimulation also suppressed their spontaneous activity. SLN stimulation elicited in all 17 pharyngeal expiratory-related units tested a short latency (range 0 to 8 ms) reduction of activity, followed in 7 units by an increase in activity. SLN stimulation occasionally evoked single or rhythmic multifibre bursts in the vagal pharyngeal filaments. These bursts, involving expiratory-related units, likely correspond to the buccopharyngeal stage of swallowing.     

Reflex prolongation of stage I of expiration

Experiments were performed on anesthetized cats to test the theory that the interval between phrenic bursts is comprised of two phases, stage I and stage II of expiration. Evidence that these represent two separate neural phases of the central respiratory rhythm was provided by the extent to which stage duration is controlled individually when tested by superior laryngeal, vagus and carotid sinus nerve stimulation. Membrane potential trajectories of bulbar postinspiratory neurons were used to identify the timing of respiratory phases.Stimulation of the superior laryngeal, vagus and carotid sinus nerves during stage I of expiration prolonged the period of depolarization in postinspiratory neurons without significantly changing the durations of either stage II expiratory or inspiratory inhibition, indicating a fairly selective prolongation of the first stage of expiration. Changes in subglottic pressure, insufflation of smoke into the upper airway, application of water to the larynx or rapid inflation of the lungs produced similar effects. Sustained tetanic stimulation of superior laryngeal and vagus nerves arrested the respiratory rhythm in stage I of expiration. Membrane potentials in postinspiratory, inspiratory and expiratory neurons were indicative of a prolonged postinspiratory period. Thus, such an arrhythmia can be described as a postinspiratory apneic state of the central oscillator. The effects of carotid sinus nerve stimulation reversed when the stimulus was applied during stage II expiration. This was accompanied by corresponding changes in the membrane potential trajectories in postinspiratory neurons.The results manifest a ternary central respiratory cycle with two individually controlled phases occurring between inspiratory bursts.     

Synaptic interactions between respiratory neurons during inspiratory on-switching evoked by vagal stimulation in decerebrate cats

To elucidate neuronal mechanisms underlying phase-switching from expiration to inspiration, or inspiratory on-switching (IonS), postsynaptic potentials (PSPs) of bulbar respiratory neurons together with phrenic nerve discharges were recorded during IonS evoked by vagal stimulation in decerebrate and vagotomized cats. A single shock stimulation of the vagus nerve applied at late-expiration developed an inspiratory discharge in the phrenic neurogram after a latency of 79+/-11 ms (n = 11). Preceding this evoked inspiratory discharge, a triphasic response was induced, consisting of an early silence (phase 1 silence), a transient burst discharge (phase 2 discharge) and a late pause (phase 3 pause). During phase 1 silence, IPSPs occurred in augmenting inspiratory (aug-I) and expiratory (E2) neurons, and EPSPs in postinspiratory (PI) neurons. During phase 2 discharge, EPSPs arose in aug-I neurons and IPSPs in PI and E2 neurons. These initial biphasic PSPs were comparable with those during inspiratory off-switching evoked by the same stimulation applied at late-inspiration. In both on- and off-switching, phase-transition in respiratory neuronal activities started to arise concomitantly with the phrenic phase 3 pause. These results suggest that vagal inputs initially produce a non-specific, biphasic response in bulbar respiratory neurons, which consecutively activates a more specific process connected to IonS.     

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.     

Augmentation of muscle nociceptive respiratory reflex facilitation by vagal afferents

Vagal influence on the facilitation of phrenic neural activity during respiratory phase-locked, gastrocnemius muscle nerve nociceptive electrical stimulation was examined in anesthetized, glomectomized, paralyzed, and artificially ventilated cats. (1) In the vagi-intact state, respiratory reflex facilitation was characterized by a sharp rise in peak amplitude, maximum rate of rise or slope, and mean rate of rise of integrated phrenic nerve activity. This was greater during inspiratory phase-locked (T1-locked) muscle nerve electrical stimulation than during expiratory phase-locked (TE-locked) muscle nerve electrical stimulation. "Evoked post-inspiratory phrenic activity" during the early expiratory phase was also observed during TE-locked muscle nerve electrical stimulation. (2) Bilateral vagotomy significantly attenuated the respiratory facilitation during both T1- and TE-locked muscle nerve electrical stimulation. In particular, the "evoked post-inspiratory phrenic activity" during TE-locked muscle nerve electrical stimulation was also attenuated or almost completely abolished. (3) Conditioning electrical stimulation of the vagus nerve revealed facilitatory reflexes which co-exist with inspiratory inhibitory reflexes. (4) The "evoked post-inspiratory phrenic activity" during TE-locked muscle nerve electrical stimulation, which was attenuated or abolished after vagotomy, was restored after vagal T1-locked conditioning stimuli combined with TE-locked muscle nerve electrical stimulation. The results suggest that vagal facilitatory reflexes augment the respiratory reflex facilitation during muscle nociceptive stimulation.     

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     

Activity of dorsal respiratory group inspiratory neurons during laryngeal-induced fictive coughing and swallowing in decerebrate cats

Membrane potential changes and/or discharges from 36 inspiratory neurons were recorded intracellularly in the dorsal respiratory group (DRG; i.e., the ventrolateral subdivision of the nucleus tractus solitarii) in decerebrate, paralyzed, and ventilated cats. Electrical activities were recorded from both somata (n=10) and axons (n=26). Activities during quiet breathing were compared with those observed during fictive coughing and swallowing evoked by repetitive electrical stimulation of afferent fibers of the superior laryngeal nerve (SLN). These nonrespiratory behaviors were evident in paralyzed animals as characteristic discharge patterns of the phrenic, abdominal, and hypoglossal nerves. Twenty-six neurons exhibiting antidromic action potentials in response to electrical stimuli applied to the cervical (C3–5) spinal cord were classified as inspiratory bulbospinal neurons (IBSNs). These neurons were considered as premotoneurons. The remaining 10 inspiratory neurons (INAA) were not antidromically activated by electrical stimuli applied to either cervical spinal cord or ipsilateral cervical vagus. These neurons are thought to be propriobulbar neurons. We recorded the activity of 31 DRG inspiratory neurons (24 IBSNs and 7 I-NAA) during coughing. All but one (a late-recruited IBSN) discharged a burst of action potentials during the coughing-related phrenic nerve activity. Typically, ramp-like membrane depolarization trajectories and discharge frequencies during coughing were similar to those observed during inspiration. We recorded the activity of 33 DRG inspiratory neurons (23 IBSNs and 10 I-NAA) during swallowing. Most (28/33) neurons were briefly activated, i.e., discharged a burst of action potentials during swallowing, but peak discharge frequency decreased compared with that measured during inspiration. The membrane potentials of nine somata exhibited a brief bell-shaped depolarization during swallowing, the amplitude of which was similar to that observed during inspiration. These results suggest that some inspiratory premotoneurons and propriobulbar neurons of the DRG might be involved in nonrespiratory motor activities, even if clearly antagonistic to breathing (e.g., swallowing). We postulate the existence in the medulla oblongata of adult mammals of neurons exhibiting a functional flexibility.     

Patterns of spontaneous and reflexly-induced activity in phrenic and intercostal motoneurons

Summary The discharge frequencies of 35 single phrenic and 13 inspiratory intercostal motoneurons were recorded in anaesthetised paralysed cats. Chemical stimulation by asphyxia or hypercapnia increased the discharge frequency and number of motoneurons active within each inspiratory discharge without altering the general pattern of respiratory activity, but mechanical stimulation of the epipharynx and electrical stimulation of the pharyngeal branch of the glossopharyngeal nerve caused repetitive bursts of very high frequency (up to 400 impulses/ sec) in inspiratory motoneurons, with disruption of their normal phasic activity. The latency of the motoneuron response to electrical stimulation of the glossopharyngeal nerve ranged from 15–30 msec and varied with respiratory phase, being shorter during spontaneous inspiratory activity.Phrenic motoneurons were divided according to their order of recruitment during inspiratory activity, and the later recruited (high-threshold) units had significantly larger spike amplitudes than motoneurons which discharged throughout inspiration. High-threshold motoneurons also achieved higher maximum discharge frequencies in response to electrical stimulation of the glossopharyngeal nerve, and it is suggested that these properties are important in increasing the tension developed by respiratory muscles near the end of inspiration when there is greater elastic resistance to lung inflation.     

Anatomical basis of the risk of injury to the right laryngeal recurrent nerve during thoracic surgery

Purpose

Despite the intrathoracic part being short, the right laryngeal recurrent nerve is often injured during thoracic surgery. The aim of this cadaver study was to understand the mechanisms of right laryngeal recurrent nerve injuries during thoracic surgery and to describe anatomical landmarks for its preservation.

Methods

Dissections were performed on 10 fresh human cadavers. A right anterolateral thoracic wall segment was removed, preserving the first rib. Dissections were carried out to identify the following structures: first rib, esophagus, trachea, right main bronchus, right brachiocephalic and subclavian vessels, azygos vein, phrenic nerve, vagus nerve, and right laryngeal recurrent nerve.

Results

The distance between the origin of the right laryngeal recurrent nerve and its adjacent structures was assessed. Moderate traction of the thoracic part of the vagus nerve resulted in a downward translation of the right laryngeal recurrent nerve’s origin. In such conditions, the right laryngeal recurrent nerve’s origin was distant of 14.8?mm (±2.89?mm) from the subclavian artery.

Conclusions

Intraoperative incidence of right laryngeal recurrent nerve direct injury could be decreased by understanding the detailed course of its intrathoracic part. Moreover, traction on the intrathoracic part of the right vagus nerve may result in indirect lesions of the right laryngeal recurrent nerve: stretch induced lesions and nerve vasculature’s lesions.     

Peripheral chemoreceptor inputs to medullary inspiratory and postinspiratory neurons of cats

The effect of peripheral chemoreceptor activation on inspiratory and postinspiratory medullary neurons was investigated using intracellular recording techniques. Peripheral chemoreceptors were activated by injecting CO₂ saturated 1 N bicarbonate solution into the lingual artery or by electrically stimulating the carotid sinus nerve. Injections of 20–300 l bicarbonate solution evoked changes in respiratory frequency and in peak phrenic nerve discharge. The membrane potential of inspiratory alpha neurons, whether bulbospinal or not and independent of their anatomic location, was decreased during inspiration. A sequence of compound excitatory and inhibitory effects were observed when the stimulus was given during the postinspiratory and expiratory phases of the respiratory cycle. Inspiratory beta- and late-inspiratory neurons, however, were inhibited by peripheral chemoreceptor activation. Postinspiratory neurons were strongly activated during postinspiration. Neither class of respiratory neurons were shown to receive direct synaptic inputs from the peripheral chemoreceptors as tested by electrical stimulation of the carotid sinus nerve and signal averaging of the respiratory neuron membrane potential. The experiments revealed differential influences of afferent chemoreceptor activity on various components of the respiratory network. We conclude that chemoreceptor afferents activate non-respiratory modulated medullary neurons which, in turn, activate or inhibit various neurons of the medullary respiratory control network. The responses of each type of respiratory neuron to chemoreceptors afferents may then be considered in the context of this direct interaction as well as the network interactions of the various cells.     

Modification by chemical stimuli of temporal difference in the onset of inspiratory activity between vagal (superior laryngeal) or hypoglossal and phrenic nerves of the rat

Temporal differences in the onset of inspiratory activities between the efferent vagal (superior laryngeal, Xsl) or hypoglossal (XII) and phrenic (Phr) nerves were measured at various levels of chemical stimuli in the halothane-anesthetized, vagotomized, and artificially ventilated rat. The onset of Xsl (XII) inspiratory activities always preceded the abrupt start of the Phr discharge. Hyperoxic hypocapnia due to hyperventilation delayed the start of inspiratory activity (reduction in respiratory frequency) and shortened the difference in onset time between the cranial (Xsl, XII) and Phr nerve discharges (Td). During respiratory stimulation due to asphyxia (progressive hypoxia and hypercapnia), the start of Xsl (XII) inspiratory activity became progressively earlier than that of Phr discharge, which extremely prolonged the Td. Severe asphyxia, however, retarded the start of inspiratory activities with accompanying long Td and slow respiratory frequency. The early but gradually augmenting inspiratory activity of the Xsl (XII) nerve was always followed by large bursts synchronized with Phr discharges during altered chemical stimuli. The termination of inspiratory activity, which occurred simultaneously in the three respiratory nerves, was not significantly affected by changes in chemical stimuli except for extreme hypocapnia. The results indicate that changes in chemical stimuli not only alter the start of inspiratory activity but also influence the transition from the initial slow onset to the final synchronized inspiratory activity in the Xsl (XII) nerve. The apparent dissociation of the onset time between the Xsl (XII) and Phr nerve discharges shows that the temporal aspect of the brain stem process(es) for starting inspiratory activities may not be determined from the trajectory of Phr discharges only.     

Respiratory modulation of the cutaneous somatosympathetic reflex in normotensive (WKY) and in spontaneously hypertensive rats (SHR): species and strain-dependent patterns

In 6 normotensive Wistar-Kyoto (WKY) and 6 spontaneously hypertensive rats (SHRs) anesthetized with urethane and chloralose, paralyzed, artificially ventilated, vagotomized with carotid sinus nerves bilaterally cut, somatosympathetic reflex discharges were recorded in cervical and renal nerves by stimulating group II and III cutaneous afferents in the sural nerve. Only a long-circuited, late supraspinal component reflex discharge could be elicited. After averaging the responses evoked by random stimulation, the latency of the reflex discharge was significantly longer in the renal than in the cervical sympathetic nerve, equally in the WKY rat and in SHR. In WKY rats the peak of sympathetic discharge corresponded to early expiration, whereas in SHRs--to late inspiratory phase. The duration of the reflex discharge elicited in inspiration was greater in SHR than in WKY rats. In WKY rats stimuli applied during phrenic discharge produced a reflex response of longer latency and of reduced amplitude than those applied in expiration. In SHRs the latency of the reflex response in the sympathetic cervical nerve was shorter during inspiration than in expiratory phase. The timing of the sympathetic reflex responsiveness within respiratory cycle in SHR and in WKY rats corresponded to strain-dependent opposite respiratory synchronization pattern of the spontaneous sympathetic activity characterizing each strain. No respiratory modulation of the somatosympathetic reflex was observed in the renal nerve of SHR. It is concluded that both spontaneous and evoked sympathetic activity is synchronized differently in SHR and in WKY rats and this difference is both species- and strain-dependent.     

Roles of vagal afferents on discharge patterns and CO2-responsiveness of efferent superior laryngeal, hypoglossal, and phrenic respiratory activities in anesthetized rats

Discharge patterns and CO2-responsiveness of the efferent respiratory activities in the superior laryngeal (Xsl), hypoglossal (XII), and phrenic (Phr) nerves were compared between vagi-intact and -denervated rats. Bilateral cervical vagotomy decreased the respiratory frequency (f), minute Phr activity (peak integrated Phr activity X f) and consequently elevated end-tidal PCO2 (PETCO2). Augmentation of the peak inspiratory activity following vagotomy was much larger in the Xsl and XII nerves than that in the Phr nerve. After vagotomy, the time delay from the onset of inspiratory activities in the Xsl or XII nerve to the onset of the Phr bursts was greatly prolonged. While in the vagi-intact rats the peak inspiratory activities of these cranial nerves were not increased in response to elevated PETCO2, the activities, in particular of the XII nerve, were augmented by high PETCO2 in the absence of vagal afferents. These results suggested that the vagal afferents inhibit not only phasic Phr discharges but also inspiratory output neurons in the Xsl or XII motor nuclei being activated in normo- and hypercapnia and that they facilitate temporally the onset and progress of inspiratory activities in various groups of respiratory output neurons.