Phrenic Discharge Research Articles

Neuromuscular blockade enhances phrenic nerve activity during high-frequency ventilation.

Phrenic nerve activity was monitored in anesthetized cats during high-frequency ventilation (HFV). Rhythmic phrenic discharge disappeared during HFV in all animals at normal arterial PCO2 levels. Rhythmic activity returned after neuromuscular blockade in the vagally intact animal. Although vagotomy alone also restored phrenic discharge, this activity was further enhanced by subsequent neuromuscular blockade. Therefore we suggest that apnea during HFV results from inspiratory inhibition mediated by both chest wall and vagal afferent mechanisms.

Characterization of respiratory-modulated activities of hypoglossal motoneurons.

In decerebrate, vagotomized, paralyzed, and ventilated cats, activities of the phrenic nerve and single hypoglossal nerve fibers were monitored. The great majority of hypoglossal neuronal activities were inspiratory (I), discharging during a period approximating that of phrenic. Many were not active at normocapnia but were recruited in hypercapnia or hypoxia. Once recruited, discharge frequencies, which rose quickly to near maximal levels in early to midinspiration, significantly increased with further augmentations of drive. Also, the onset of activities became progressively earlier, compared with phrenic discharge, in hypercapnia or hypoxia. Smaller numbers of hypoglossal fiber activities, having inspiratory-expiratory (I-E), expiratory (E), expiratory-inspiratory (E-I), or tonic discharge patterns, were also recorded. Activities of E, I-E, and those I fibers that became I-E in high drive may underlie the early burst of expiratory activity of the hypoglossal nerve. It is concluded that the firing and recruitment patterns of hypoglossal neurons differ from those of phrenic motoneurons. However, responses to chemoreceptor stimuli are similar among the two neuronal groups.

Inhibitory effects on fast sympathetic rhythms

In decerebrate cats, the effects of barbiturate anesthesia and of pulmonary afferent activity (produced by lung inflation) on fast (ca. 10/s) rhythms in sympathetic efferent discharges (cervical sympathetic and splanchnic) were analyzed. These inhibitory influences, in addition to reducing overall activity, eliminated or drastically reduced the highest frequency oscillations. Barbiturate anesthesia also markedly reduced high frequency oscillations (ca. 100/s) in phrenic discharge. Apparently, then, the occurrence of fast neural rhythms is dependent on the level of tonic excitatory activity.

Baroreceptor modulation of inspiratory termination by intercostal nerve stimulation

The influence of carotid sinus baroreceptor activity on the termination of inspiration by intercostal nerve stimulatiion was assessed in decerebrate cats which were paralyzed, artificially ventilated and bilaterally vagotomized. The carotid sinus was vascularly isolated bilaterally so that carotid sinus pressure could be precisely controlled independent of the systemic arterial pressure. Inspiratory activity was monitored by a phrenic neurogram. The threshold current at which electrical stimulation of the T6 intercostal nerve terminated phrenic neural activity determined by stimulating T6 intercostal nerve at 10 different delays from the onset of phrenic discharge. An increase in mean carotid sinus pressure from 100 to 150 mm Hg decreased the threshold current required to terminate inspiration at each delay. Similarly, a decrease in mean carotid sinus pressure from 100 to 50 mm Hg increased the threshold current. Alteration of the systematic arterial pressure (independent of the carotid sinus pressure) by norepinephrine administration did not alter the threshold current. There results demonstrate that alterations in carotid sinus baroreceptor activity have a distinct effects on the mechanisms governing inspiratory termination.

Inspiratory onset or termination induced by electrical stimulation of the brain

In anesthetized cats, electrical stimulation of the cerebral cortex and subcortical structures with short trains could induce onset or termination of activity of the phrenic nerve. Onset of phrenic discharge was obtained following stimulation of the primary sensory areas of the cerebral cortex, the periaqueductal gray, the ponto-mesencephalic reticular formation, the parabrachial nucleus, the vestibular nucleus, and the fastigial nucleus. When these structures were stimulated by repetitive trains at frequencies of 1–5 Hz, the respiratory rhythm was entrained to these same frequencies. The phrenic discharge during these repetitive stimulations exhibited a decrementing pattern similar to that during thermal polypnea. Termination of phrenic activity was obtained upon stimulation of the motor and visceral cortices, the internal capsule, the pyramidal tract, the red nucleus, the rubrospinal tract and the motor nucleus of the trigeminal nerve. Stimulation of these latter structures by repetitive trains resulted in a temporary or permanent arrest of phrenic discharge. These results are discussed in the context of the possible roles of medullary respiratory neurons in the onset or termination of inspiratory activity.

Ventilatory responses to mechanical loads in cervical cord-injured humans.

Load compensation in 29 cervical cord-injured men was inferred from the difference between actual first-breath responses to graded elastic and resistive loads and those calculated assuming identical respiratory muscle pressure (Pmus) wave forms in the unloaded and loaded states (i.e., the passive prediction). At every load, respiratory frequency (f) and tidal volume (VT) responses from different individuals formed a continuum ranging from a weak VT defense coupled with an increased f to a strong VT defense coupled with a decreased f. Individual VT responses ranged from values smaller than the passive prediction to values exceeding control, suggesting that phrenic motoneuron output was not constant but decreased in some subjects and increased in others. In support of this hypothesis, 1) individual VT responses varied with inspiratory duration (TI; P less than 0.01); 2) TI responses indicated some subjects prematurely terminated their phrenic motoneuron output, whereas others prolonged it; 3) VT/TI responses suggested that some subjects modified the discharge frequency of their phrenic output; and 4) rib cage instability contributed insignificantly to these responses. These findings, which are similar to those reported for normal men, indicate that 1) afferent pathways from the rib cage and intercostal muscles are not required for the initiation of a range of ventilatory responses to loads; and 2) afferent pathways from the mouth, lung, and/or diaphragm are sufficient, by themselves, to modulate the duration, intensity, and timing of the phrenic discharge during the first loaded breath.

Effect of thoracic deafferentation on load-compensating mechanisms in humans.

First-breath responses to graded elastic (delta E) and resistive (delta R) loads in 29 cervical cord-injured and 80 normal men were compared with those predicted assuming identical respiratory muscle pressure (Pmus) wave forms in the unloaded and loaded states. The cord-injured group's mean actual and predicted inspiratory duration (TI) responses were equal, indicating that the average duration of their phrenic discharge remained constant during both delta E and delta R. Their mean expiratory duration (TE) responses fell short of predictions with delta E but exceeded predictions with delta R, signifying that a neural mechanism hastened inspiration following delta E but postponed it following delta R. TE/(pred TE) values (an index of phrenic timing) from different loads were proportional to concomitant TI responses but not to indices of diaphragmatic force [peak Pmus, (VT/TI)/(pred VT/TI)], movement (VT, VT/TI), or duration of contraction [TI/(pred TI)]. These findings suggest that oropharyngeal and/or pulmonary receptors signaling airflow duration, rather than diaphragmatic length or tension receptors, adjust phrenic motoneuron timing during mechanical loading. The cord-injured group produced a normal tidal volume (VT) defense coupled with a depressed frequency (f) response to delta E and, conversely, a weak VT defense coupled with a normal f response to delta R. Since both groups' VT/TI responses surpassed predictions equally, the cord-injured group's deficit was attributable entirely to impaired regulation of TE during delta E and TI during delta R. Thus chest wall receptors modulate duration and timing, but probably not average intensity, of the phrenic output during loading. Nearly one-third of the normal, but virtually none of the cord-injured, samples prolonged TI against large delta R and shortened TI agaist large delta E, suggesting that thoracic deafferentation impairs human ability to distinguish large delta R from delta E. These latter findings support the hypothesis that chest wall afferents subserve perception of respiratory force or position in humans.

Postnatal development of the discharge pattern of phrenic motor units in the kitten

The postnatal change of the mean frequency ( F ), the maximal frequency (F M) and the onset frequency (F O) of discharge of kitten phrenic motor units was studied and compared to adult values. The latency (recruitment time) and duration of discharge of phrenic units were also analyzed. In kittens less than 3 weeks old, there were relatively few early units (latency less than or equal to 10% of phrenic discharge duration, Ti). The duration of early and late units, expressed in percentage of Ti, was the same in kittens and adult cats, and the duration of discharge of the early units was greater than that of the late units. In kittens, F , F M and F O of the early and late units were always greater than in adult cats. In adult cats, as in kittens, F , F M and F O of early units were not significantly greater than those of late units. In conclusion, the relatively small number of early units in kittens may reflect either a small number of active early bulbo-spinal neurons or may be linked to the electrical and morphological properties of phrenic motoneurons in the kitten.

Onset of inspiration in rabbit during artificial ventilation.

1. We have investigated whether pulmonary stretch receptors are the only lung receptors determining the time of onset of inspiratory efforts in anaesthetized, paralysed rabbits. 2. New Zealand White rabbits were anaesthetized, paralysed and ventilated by intermittent positive pressure with a pattern that closely followed spontaneous breathing. Inspiratory efforts were recorded as bursts of activity in a root of the phrenic nerve. Lung stretch receptors were blocked with SO2 in air. Abolition of the Breuer-Hering reflex was used as an index of stretch receptor block. 3. With stretch receptors functioning phrenic discharge invariably occurred during the deflation phase of ventilation. With stretch receptors blocked phrenic discharge occurred with no set relation to ventilation at spontaneous resting tidal volume but was locked to inflation and deflation phases of lung volume at 30% higher tidal volumes. 4. Bilateral vagotomy produced a pattern of phrenic discharge identical with that seen with stretch receptor block and low ventilating volumes. 5. Thus we have demonstrated a vagally mediated inspiratory initiating effect; it probably originates from rapidly adapting lung irritant receptors.

Effect of arterial [H+] on threshold PCO2 of the respiratory system in vagotomized and carotid sinus nerve denervated cats.

Phrenic nerve discharges were recorded as an output of respiratory activity in anaesthetized, vagotomized cats immobilized by gallamine and artificially ventilated with room air. 2. With the carotid sinus nerve (c.s.n.) intact or denervated, PcO2 threshold levels (Pth, CO2) were determined at arterial pH, varied between 7.0 and 7.6 ([H+] 25-100 nM) by successive intravenous infusions of 0.5 N-HCl or 1.0 M-NaHCO3. Ventilation was increased stepwise to induce a successive decrease in end-tidal PCO2. Pth, CO2 was defined as the level of end-tidal PCO2 at which phrenic discharges ceased. 3. With the c.s.n. intact, Pth, CO2 decreased linearly upon increasing arterial [H+]. The mean regression line, calculated from seven cats, was Pth, CO2 =-0.37 [H+] + 34.33. A similar inverse relationship was observed with the c.s.n. denervated. However, the slope of the regression line was significantly smaller, the mean regression line/eleven cats) being Pth,CO2 =-0.18 [H+]+ 35.06. 4. The relative contributions of arterial [H+] and PCO2 in stimulating the peripheral and central chemoreceptors could be estimated quantitatively. Arterial [H+] appears to be almost equally effective on both peripheral and central chemoreceptors; PCO2 acts exclusively on the central chemoreceptors. 5. Thus, the additive theory regarding the induction of respiratory activity by arterial [H+] and PCO2 was confirmed. In addition, the H+ drive was shown to be able to affect respiratory activity even in the absence of the peripheral chemoreceptors.

Respiratory oscillator entrainment by periodic vagal afferentes: an experimental test of a model.

This communication compares the well known phenomenon of respiratory driving by the respiratory pump through the Breuer Hering reflex with a model (Segundo, 1979) of a neuronal pacemaker (i.e. regularly firing) interactions via IPSP's. The assumption involves a linear dependence (“delay function”) of the postsynaptic interval lengthening (or “delay”) produced by the IPSP's on the position (or “phase”) with respect to the preceding spike of the latter's arrival. Cats anesthetized and paralized with gallamine were artificially ventilated using a computer driven respirator. The pump period and the respiratory period (identified by the phrenic discharge) corresponded to the model's presynaptic pacemaker interval and to that of the post synaptic one, respectively. The delay of the respiratory period by an inflation was related linearly and in increasing manner to the latter's phase with respect to the inspiration onset. In the steady state, plots of average respiratory period versus pump period consisted in a succession of broad “paradoxical” segments with positive slopes 3, 2, 1, 1/2, 1/3 in which respiration was locked with the pump as predicted by the model. The locked condition were less easy to reach when FACO2increased or when level of anaesthesia decreased. The limits of paradoxical segments were different when measured using pump periods that increased or using periods that decreased. There was therefore a hysteresis as if the delay function parameters changed, a behavior that was not part of the model that assumed fixed characteristics. These modifications were related to dependency of each cycle on the preceding one. The model proposed for simple neuronal pacemaker interactions can thus be applied satisfactorily to the drive of the complex respiratory neuronal oscillator by the respiratory pump through Breuer Hering reflex, providing nevertheless some additonal assumptions concerning respiratory cycle interdependency are introduced to account for the hysteresis phenomenon. The Breuer Hering reflex could be considered as the equivalent of IPSP acting on the central respiratory oscillator. FACO2increase and anesthesia level decrease produced the same effect as the addition of noise to the model's presynaptic pacemaker, thus leading to the hypothesis that they act by adding noise (e.g., randomly distributed excitatory input) at the level of Breuer Hering reflex inhibition.

Inspiratory inhibition of vagal responses to baroreceptor and chemoreceptor stimuli in the dog.

1. Single and few-fibre cardiac efferent filaments were dissected from the cervical vagus nerve of dogs anaesthetized with chloralose and paralysed with pancuronium. 2. Brief selective baroreceptor or chemoreceptor stimuli, given during the expiratory phase of the central respiratory cycle and while the lungs were motionless, evoked trains of action potentials in cardiac vagal efferent fibres. These vagal responses outlasted the duration of the stimuli by 1-3 s. 3. Brief selective baroreceptor or chemoreceptor stimuli given during the inspiratory phase of the central respiratory cycle (monitored as phrenic discharge) but while the lungs were motionless, failed to evoke reflex increases in discharge. Background vagal discharge was also inhibited during central inspiratory activity. 4. Brief baroreceptor or chemoreceptor stimuli given during lung inflation but in the expiratory phase of the central respiratory cycle (phrenic silence), also failed to evoke any reflex increase in discharge, but left resting vagal tone relatively unaffected. Only when vagal tone was high was it markedly inhibited by lung inflation, in the absence of central inspiratory activity. 5. A point of contrast between the inhibitory effects of lung inflation and of central inspiratory activity is that both tonic and reflexly evoked vagal discharge are inhibited during central inspiratory activity, but lung inflation more markedly inhibits reflexly evoked vagal discharge than tonic vagal discharge. 6. A model is suggested to explain the different mechanisms of inhibition by lung inflation and by central inspiratory activity.

Apneusis and apnea after parabrachial or Kölliker-Fuse N. Lesion; Influence of wakefulness

Comparisons were made between the effects of bilateral lesions of either the nucleus parabrachialis medialis (NPBM) or the Kölliker-Fuse (KF) nuclei in bivagotomized, spinalized and immobilized cats. In a first group animals were electrolytically decerebrated; in a second group animals were locally anaesthetized and atraumatically restrained (semi-chronic encéphale isolé preparation). Lesions resulted in: (1) a marked increase in Ti (apneusis); (2) 50–80% decrease in amplitude of the integrated phrenic discharge (IPD); (3) variable lengthening of Te. Following KF lesion, effects were significantly larger on Te in the decerebrate group, and on Ti in the encéphale isolé group. In the encéphale isolé group awakening reduced Te and Ti and brought them close to their prelesion values following both NPBM and KF lesion; on the other hand light sleep induced by pentobarbital led to expiratory apnea after KF lesion and reduced IPD amplitude to zero after NPBM lesion. It is proposed that the onset, tonic drive and cut off of the I discharge are normally controlled by three differently weighted influences originating from NPBM, KF and reticular formation respectively.

Respiratory reflexes evoked by tracheal distension

In 13 dogs that were anesthetized and ventilated through an endotracheal tube, segments of either the intrathoracic (ITT) or extrathoracic trachea (ETT) were distended by over-inflating the sealing cuff within the first half of an inspiration and maintaining this overinflation for two breathing cycles. ITT distension caused a significant prolongation of the expiratory duration (TE) of the first challenged breath in 12 of the 13 dogs. ETT distension prolonged the TE in only 5 of the 13 dogs. An inhibition of inspiration resulting in shortened inspiratory time and reduced peak phrenic amplitude (PPA) was measured in three experiments. In six other experiments, there was only a transient decrease in phrenic discharge, which immediately resumed. In the remaining four experiments, the inspiratory burst was unaffected. After vagotomy, ITT distension shortened TE in 8 of the 13 dogs. ETT distension was ineffective in 10 out of 11 experiments; in the remaining experiment TE was significantly lengthened. No significant effects were elicited on TI and PPA by either ITT or ETT distension. These results could be explained by the known behavior of tracheal receptors and could indicate the presence of extravagal influences.

Characteristics of sustained graded inspiratory inhibition by phasic lung volume changes.

The dynamic characteristics of graded reversible inspiratory inhibition by vagal feedback were investigated in pentobarbital-anesthetized paralyzed cats, ventilated with a servo respirator. The volume and time associated with various levels of graded inhibition were determined by using a series of constant-flow lung inflations. Protracted phrenic inhibition was produced by lung inflation, which was arrested when the phrenic discharge was partially inhibited. Thereafter, the volume was withdrawn along a trajectory that approximately paralleled the fall in inhibitory threshold. This volume-withdrawal trajectory would be expected to produce a sustained nearly constant level of inhibition based on the results determined from the constant-flow inflations. However, the observed inhibition exceeded that expected, increasing to a maximum and then decreasing to expected values over a period ranging from 1 to 2 s in most animals. This excess inhibition cannot be attributed to the known dynamic properties of pulmonary stretch receptors; their activity should be reduced, for any particular lung volume, during the volume withdrawal maneuver. These results suggest a central integrative processing of vagal afferent activity that causes inhibition to lag volume. This delay acts to promote inspiratory off-switching because it prevents the development of a protracted period of reversible inhibition.

Central respiratory and circulatory depression caused by intravascular saxitoxin.

1 In cats anaesthetized with pentobarbitone and vagotomized, observations were made on the phrenic nerve action potential and the diaphragm electromyogram (EMG) at constant end-tidal Pco(2). Arterial blood pressure was stabilized by intravenous infusions of noradrenaline.2 Intravenous administration of saxitoxin (STX) initially abolished respiratory activity in the EMG and caused a slowing of oscillation in the central phrenic neurogram. Additional STX produced apneustic phrenic discharges followed by a progressive loss of nerve action potentials.3 The inspiratory centre in the medulla oblongata was stimulated electrically to evoke a sustained phrenic nerve discharge. STX, given intravenously, resulted in the elimination of spontaneous nerve activity without interfering with the evoked response.4 The cephalic intravascular infusion of STX into a carotid or vertebral artery depressed spontaneous respiratory activity while sparing EMG activity evoked by electrical stimulation of the intact phrenic nerve.5 Spontaneous respiratory discharge in the phrenic nerve was eliminated by smaller doses of STX administered intra-arterially than were required intravenously. In addition, onset of and recovery from neural silence occurred faster following intra-arterial injection of STX.6 Depressant effects on arterial blood pressure coincided with those on respiration when STX was given intra-arterially.7 An electrophysiological assay on frog sartorius muscle was used to measure STX in the cerebrospinal fluid. Levels of STX detected were proportional to amounts of the toxin infused intra-arterially.8 It is concluded that STX exchanges rapidly between blood and brain to bring about central depression and this adds to its peripheral paralytic actions.

Phrenic activity during severe hypercapnia in vagotomized rabbits.

The central control mechanism of respiratory frequency under varied alveolar carbon dioxide pressure (PACO2 20--200 Torr) was investigated in anesthetized, vagotomized, immobilized, and artificially ventilated rabbits. Central inspiratory activity indicated by phrenic motor discharge was tolerant of the extensive hypercapnia. Under light anesthesia the respiratory frequency (f) decreased in a hyperbolic fashion with increasing PACO2. Under deeper anesthesia or after mesencephalic decerebration the hyperbolic f response to PACO2 was abolished or changed to a hill-type f response (initial increase and subsequent decrease in f) and, on the average, the changes in frequency were much less. We conclude that in the absence of vagal control the respiratory frequency is primarily determined by 1) the periodicity of the bulbopontine inspiratory activity, which is little dependent on PACO2, and 2) a suprapontine acceleratory mechanism, which is depressed by increased PACO2 and highly sensitive to anesthetics. The mechanism of changes in the type of f response to CO2 is discussed.

Comparison of phrenic motoneuron responses to hypercapnia and isocapnic hypoxia.

This study was undertaken to compare phrenic motoneuron responses to hypercapnia and isocapnic hypoxia. Efferent activity of single phrenic nerve fibers was recorded with that of the contralateral phrenic nerve in decerebrate cats which were vagotomized, paralyzed, and artificially ventilated. At normocapnia in hyperoxia, single phrenic fibers were distributed into approximately equal "early" and "late" populations according to their onset of activity relative to the period of the phrenic burst. Elevations of PACO2 or diminutions of PAO2 resulted in progressive increases in the number of spikes per respiratory cycle and decreases in the modal interspike interval for both early and late units. Moreover, either stimulus caused an onset of late unit activity at progressively earlier portions of inspiration. At equivalent levels of peak integrated phrenic discharge achieved at normocapnia or hypercapnia as compared to normoxia or hypoxia, there were no differences in activity patterns for either early or late units. It is concluded that hypoxia-induced alterations in the activity of single phrenic motoneurons are identical to those changes resulting from hypercapnia.

Reflex influences from the extrathoracic trachea during airway occlusion

We have performed experiments in 26 dogs anesthetized with pentobarbital and fitted with an endotracheal tube. The inflatable cuff of this tube was positioned either at the level of the cricoid cartilage or at the thoracic inlet. In this latter situation the extrathoracic trachea (E.T.T.) is not subjected to any change in transmural pressure both during breathing and airway occlusion. We have compared the inspiratory output in term of the integrated phrenic discharge during airway occlusion at FRC with the tracheal tube positioned at either one of the two levels. In most of the experiments (16 out of 26) the inspiratory output during airway occlusion is significantly greater (157%) when the E.T.T. is not by-passed and this different disappears after bilateral vagotomy. We interpret these results by the asymmetrical response of the tracheal stretch receptors to psitive and negative transmural pressure (Pt); most of these receptors are active at FRC and decrease their activity at low negative Pt, as that attained in the first occlued breath. These results seem to suggest that the reflex influences from the extrathoracic tracheal receptors on the inspiratory output are similar to those originating from the intrathoracic airway stretch receptors.

Differential alteration by hypercapnia and hypoxia of the apneustic respiratory pattern in decerebrate cats

1. A combination of bilateral lesions within the nucleus parabrachialis medialis complex (n.p.b.m.) and bilateral vagotomy typically resulted in an apneustic respiratory pattern in decerebrate and paralysed cats. Integrated efferent phrenic nerve activity was recorded as an index of the respiratory rhythm.2. Changes in components of this apneustic breathing cycle were evaluated in response to steady-state hypercapnia and hypoxia. The components evaluated were (a) the period of phrenic discharge (inspiratory time, T(I)), (b) the period of no detectable phrenic activity (expiratory time, T(E)), (c) the total duration of the apneustic respiratory cycle (T(TOT), the sum of T(I) and T(E)), and (d) the average height of the integrated phrenic nerve activity (apneustic depth).3. Elevations of P(A, CO2) from values below 45 torr to 50-60 torr, under both hyperoxic and normoxic conditions, resulted in significant elevations of T(I), T(E), T(TOT) and depth. Further P(A, CO2) elevations to approximately 70 torr caused no change, or frequently, a decrease in T(I), T(E) and T(TOT); the apneustic depth increased in most animals.4. Diminutions in P(A, O2) from normoxic to hypoxic levels at isocapnia typically caused an increase in apneustic depth and, concomitantly, significant decreases in T(I), T(E) and T(TOT).5. Pharmacological stimulation of the carotid chemoreceptors by intracarotid administration of 1.0-20 mug NaCN produced a premature onset of phrenic nerve activity if delivered during the expiratory period. Such NaCN administrations, delivered during the inspiratory phase, resulted in an augmentation of the integrated phrenic discharge and a premature termination of phrenic activity. Carotid sinus nerve section eliminated the response to NaCN administration.6. In experimental animals having bilateral carotid sinus nerve section, normoxic hypercapnia caused similar changes in the apneustic breathing pattern to those recorded in cats having intact carotid chemoreceptors. However, isocapnic hypoxia induced time-dependent changes in the pattern of phrenic discharge including diminutions in depth, an onset of gasping-type activity, or expiratory apnea.7. In a few animals, bilateral n.p.b.m. lesions and bilateral vagotomy resulted in expiratory apnea which was continuous as long as ventilation with air was maintained. This expiratory apnea was replaced by an apneustic breathing pattern following diminutions of P(A, O2) below 90 torr. This establishment of an apneustic breathing pattern by hypoxia was observed both in animals having intact, as well as sectioned, carotid sinus nerves. This expiratory apnea could also be terminated by a single apneustic inspiration following general somatic stimulation or, in cats having intact carotid chemoreceptors, following intracarotid NaCN administration.8. It is concluded that hypercapnia and hypoxia produce differential alterations of the apneustic breathing pattern in decerebrate cats. Further, the hypoxia-induced changes are considered to represent the net result of carotid chemoreceptor stimulation and brain stem depression. The results of this study are considered in the context of proposed mechanisms for phase-switching of the respiratory cycle.