Characteristics of inspiratory inhibition by phasic volume feedback in cats

The dependence of phrenic efferent discharge on vagal-volume feedback was examined in barbiturate-anesthetized, paralyzed cats ventilated by a phrenic-driven servo respirator. The characteristics of the respiratory were altered for a single breath, and the resulting change in phrenic activity was quantitated by comparison with phrenic activity without phasic volume feedback. The relation between volume feedback and phrenic inhibition was determined both when inspiratory termination occurred during the rising phase of phrenic discharge and during the plateau observed with barbiturate-induced apneusis. Inhibition of inspiratory activity occurred only when lung volume exceeded a time-dependent threshold. Above this threshold, andextending over a substantial volume range, volume feedback caused graded and reversible inhibition of phrenic discharge. The threshold for graded inhibition declined progressively during the inspiratory phase, showing no obvious relation to the level of inspiratory activity. At any particular time, the relation between volume and phrenic inhibition was convex to the volume axis, and the slope of the relationship increased with inspiratory time. The results indicate that a) volume feedback inhibits inspiration in a graded manner, b) partial inhibition of phrenic activity renders it more susceptible to additional inhibition, and c) inhibitory effectiveness of volume feedback increases with time.     

Phase locking of the respiratory rhythm in cats to a mechanical ventilator

Mechanical ventilation of paralyzed, pentobarbital-anesthetized adult cats was performed while recording phrenic nerve activity. The periodic changes in lung volume owing to mechanical ventilation affected the rhythm of central respiratory activity, resulting in a variety of regular and irregular patterns of coupling between respiratory system output, monitored by phrenic activity, and the mechanical ventilator. Phase-locked patterns, in which phrenic burst onset occurred at specific and repetitive phase(s) of the mechanical ventilator, with ratios of ventilator frequency: phrenic burst frequency of 1:2, 1:1, 3:2, 2:1, and 3:1 were observed. Regular and irregular patterns occurred over specific ranges of frequency and volume of the mechanical ventilator. A careful study was made of the 1:1 phase locking as the frequency and inflation volume of the mechanical ventilator were changed. The inspiratory time (TI) was defined as the interval between the time when phrenic activity began to rise and the onset of its rapid decline, and the expiratory time (TE) as the time between inspirations. In the 1:1 phase-locking region, as the frequency of the ventilator was increased both TI and TE decreased, and the phase of phrenic onset in the ventilator cycle changed. During ventilation with frequencies higher than the intrinsic phrenic frequency (initial burst frequency of phrenic activity with the ventilator turned off) inspiratory activity was prematurely terminated by lung inflation (Hering-Breuer inspiratory inhibitory reflex). During ventilation with frequencies lower than the intrinsic phrenic frequency, the onset of phrenic activity was delayed (TE was prolonged) by lung inflation (Hering-Breuer expiratory promoting reflex).     

Effect of pulmonary arterial PCO2 on breathing pattern

We studied breathing patterns and tidal volume (VT)-inspiratory time (TI) relationships at three steady-state levels of pulmonary arterial PCO2 (PpCO2) in 10 anesthetized dogs. To accomplish this we isolated and then separately pump perfused the pulmonary and systemic circulations, which allowed us to control blood gases in each circuit independently. To ventilate the lungs at a rate and depth determined by central drive, we used an electronically controlled positive-pressure ventilator driven by inspiratory phrenic neural activity. Expiratory time (TE) varied inversely with PpCO2 over the range of PpCO2 from approximately 20 to 80 Torr. VT and TI increased with rising PpCO2 over the range from approximately 20 to 45 Torr but did not change further as PpCO2 was raised above the middle level of approximately 45 Torr. Thus minute ventilation increased as a function of TE and VT as PpCO2 was increased over the lower range and increased solely as a function of TE as PpCO2 was increased over the upper range. The VT-TI relationship shifted leftward on the time axis as PpCO2 was lowered below the middle level but did not shift in the opposite direction as PpCO2 was raised above the middle level. In addition to its effect on breathing pattern, we found that pulmonary hypocapnia depressed inspiratory drive.     

Servo respirator constructed from a positive-pressure ventilator.

We have constructed an electronically controlled respirator from three commercially available components: a positive-pressure ventilator, a recorder pen motor, and a differential amplifier. Using negative feedback derived from a tracheal pressure signal, the instrument functions as a servo respirator which provides precise control of tracheal pressure. The system's power and response characteristics are well suited for ventilation of anesthetized cats and dogs. The servo respirator can be used as an externally controlled respiratory pump which provides flexibility in selection of the parameters of the ventilatory cycle. Alternatively, it can function as a "demand" respirator which generates transthoracic pressure proportional to efferent respiratory discharge.     

Respiratory responses in reversible diaphragm paralysis

The effects of diaphragm paralysis on respiratory activity were assessed in 13 anesthetized, spontaneously breathing dogs studied in the supine position. Transient diaphragmatic paralysis was induced by bilateral phrenic nerve cooling. Respiratory activity was assessed from measurements of ventilation and from the moving time averages of electrical activity recorded from the intercostal muscles and the central end of the fifth cervical root of the phrenic nerve. The degree of diaphragm paralysis was evaluated from changes in transdiaphragmatic pressure and reflected in rib cage and abdominal displacements. Animals were studied both before and after vagotomy breathing O2, 3.5% CO2 in O2, or 7% CO2 in O2. In dogs with intact vagi, both peak and rate of rise of phrenic and inspiratory intercostal electrical activity increased progressively as transdiaphragmatic pressure fell. Tidal volume decreased and breathing frequency increased as a result of a shortening in expiratory time. Inspiratory time and ventilation were unchanged by diaphragm paralysis. These findings were the same whether O2 or CO2 in O2 was breathed. After vagotomy, no significant change in phrenic or inspiratory intercostal activity occurred with diaphragm paralysis in spite of increased arterial CO2 partial pressure. Ventilation and tidal volume decreased significantly, and respiratory timing was unchanged. These results suggest that mechanisms mediated by the vagus nerves account for the compensatory increase in respiratory electrical activity during transient diaphragm paralysis. That inspiratory time is unchanged by diaphragm paralysis whereas the rate or rise of phrenic nerve activity increases suggest that reflexes other than the Hering-Breuer reflex contribute to the increased respiratory response.     

Phrenic afferents and ventilatory control at increased end-expiratory lung volumes in cats

The role of phrenic afferents in controlling inspiratory duration (TI) at elevated end-expiratory lung volume (EEV) has been studied in pentobarbital-anesthetized, spontaneously breathing cats with intact vagi. Responses to increases in EEV, induced by imposition of an expiratory threshold load (ETL) of 10 cmH2O, were monitored before and after section of cervical dorsal roots C3-C7. The immediate (first-breath) effect of application of ETL was a prolongation of both TI and expiratory duration (TE). After 10 min of breathing against the ETL, average TI returned to control values but TE remained prolonged. Abolishing feedback from the diaphragm did not affect these responses. When steady-state responses to ETL were compared with those elicited by inhalation of 5-6% CO2 in O2, changes in EEV had, on average, no independent effect on respiratory drive (rate of rise of integrated phrenic activity), although phrenic activity increased greatly in some cats despite little or no change in arterial partial pressure of CO2. These data indicate that diaphragmatic receptors do not contribute to either the immediate (first-breath) or steady-state responses of phrenic motoneurons to increases in EEV in intact cats.     

Relationship between respiratory nerve and muscle activity and muscle force output.

To demonstrate the most satisfactory way of using electrical activities of respiratory nerves and muscles, activities of phrenic nerve and external intercostal muscle (ICM) and the airway pressure changes generated by respiratory muscle contraction were recorded in anesthetized cats during complete airway occlusion. Electrical activities were rectified, integrated and processed in terms of peak and average inspiratory rates per 0.1 s and of total activity per breath. Peak rate of phrenic nerve activity exhibited a high linear correlation (r = 0.974) with peak inspiratory pressure. Average phrenic rate showed a similar high correlation (r = 0.973). Peak rate of external ICM was linearly related to peak pressure but the correlation was less good (r = 0.915). Total phrenic activity per breath was too dependent upon inspiratory duration to be a satisfactory correlate (r = 0.674). In this experiment occlusion pressure was an index of muscle force generation and respiratory control system output. It is concluded that peak or average rates of phrenic activity provide an electrical index of output changes. On theoretical grounds, peak rate is probably better.     

Influence of inspiratory assistance on ventilatory control during moderate exercise

In five healthy subjects, we studied the effects of controlled mechanical unloading of the respiratory system on ventilatory control during moderate exercise, utilizing a modified positive-pressure ventilator (IEEE Trans. Biomed. Eng. BME-33: 361-365, 1986). We were especially interested in whether isocapnia was maintained when a portion of the normal ventilatory response to constant-load cycling was subserved by the ventilator. The mechanical unloading was achieved by "assisting" airflow throughout inspiration in a constant proportion to instantaneous flow. Two modest degrees of assistance (A1 = 1.5 and A2 = 3.0 cmH2O X l-1 X s) were imposed. The assistance caused minute ventilation (VE) to increase immediately (inspiratory time shortening and tidal volume rising) and end-tidal PCO2 (PETCO2) to fall. Some 10-15 s later, inspiratory occlusion pressure (P100) decreased, and in the new steady-state VE and PETCO2 were virtually restored to their control exercise levels. The modest residual hyperventilation [delta PETCO2 = -0.9 Torr (A1) and -1.6 Torr (A2)], which was not significant statistically, contrasted markedly with the much larger increase predicted for VE had there been no compensatory reduction in ventilatory drive (as evidenced by the fall in P100). Consistent with earlier studies utilizing resistive loading (J. Appl. Physiol. 35: 361-366, 1973 and Acta Physiol. Scand. 120: 557-565, 1984), these observations suggest that ventilatory drive during moderate exercise is controlled to compensate for modest changes in respiratory-mechanical load, so that VE is preserved at a level appropriate to metabolic rate or nearly so.     

Recovery of phrenic activity and ventilation after cervical spinal hemisection in rats.

We tested two hypotheses: 1) that the spontaneous enhancement of phrenic motor output below a C2 spinal hemisection (C2HS) is associated with plasticity in ventrolateral spinal inputs to phrenic motoneurons; and 2) that phrenic motor recovery in anesthetized rats after C2HS correlates with increased capacity to generate inspiratory volume during hypercapnia in unanesthetized rats. At 2 and 4 wk post-C2HS, ipsilateral phrenic nerve activity was recorded in anesthetized, paralyzed, vagotomized, and ventilated rats. Electrical stimulation of the ventrolateral funiculus contralateral to C2HS was used to activate crossed spinal synaptic pathway phrenic motoneurons. Inspiratory phrenic burst amplitudes ipsilateral to C2HS were larger in the 4- vs. 2-wk groups (P<0.05); however, no differences in spinally evoked compound phrenic action potentials could be detected. In unanesthetized rats, inspiratory volume and frequency were quantified using barometric plethysmography at inspired CO2 fractions between 0.0 and 0.07 (inspired O2 fraction 0.21, balance N2) before and 2, 3, and 5 wk post-C2HS. Inspiratory volume was diminished, and frequency enhanced, at 0.0 inspired CO2 fraction (P<0.05) 2-wk post-C2HS; further changes were not observed in the 3- and 5-wk groups. Inspiratory frequency during hypercapnia was unaffected by C2HS. Hypercapnic inspiratory volumes were similarly attenuated at all time points post-C2HS (P<0.05), thereby decreasing hypercapnic minute ventilation (P<0.05). Thus increases in ipsilateral phrenic activity during 4 wk post-C2HS have little impact on the capacity to generate inspiratory volume in unanesthetized rats. Enhanced crossed phrenic activity post-C2HS may reflect plasticity associated with spinal axons not activated by our ventrolateral spinal stimulation.     

Phrenic neural output during hypoxia in dogs: constant-flow ventilation vs. spontaneous breathing.

We studied the effects of removing cyclic pulmonary afferent neural information on respiratory pattern generation in anesthetized dogs. Phrenic neural output during spontaneous breathing (SB) was compared with that occurring during constant-flow ventilation (CFV) at several levels of eucapnic hypoxemia. Hypoxia caused an increase in both the frequency and the amplitude of the moving time average (MTA) phrenic neurogram during both SB and CFV. The change in frequency as arterial saturation was reduced from 90 to 60% during SB was significantly higher than that during CFV [SB, 32.3 +/- 10.9 (SD) breaths/min; CFV, 10.3 +/- 5.8 breaths/min; P = 0.001]. By contrast, the increase in the amplitude of the MTA phrenic neurogram was smaller (SB, 0.62 +/- 0.68 units; CFV, 1.35 +/- 0.81 units; P = 0.01). The changes in frequency with hypoxia during both modes of ventilation resulted primarily from a shortening of expiratory time. Both inspiratory time and expiratory time were greater during CFV than during SB, but their change in response to hypoxia was not significantly different. We conclude that the amplitude response of the MTA phrenic neurogram to hypoxia is similar to that seen during hypercapnia; in the presence of phasic afferent feedback the MTA amplitude response is decreased and the frequency response is increased relative to the response observed in the absence of phasic afferents.     

Influence of phasic afferent information on phrenic neural output during hypercapnia

We measured the moving time average (MTA) of the phrenic neurogram before and after removal of phasic afferent information from the lungs, chest wall, and oscillations in blood gases by using constant-flow ventilation (CFV). Anesthetized dogs were studied at various levels of steady-state and progressive hypercapnia during spontaneous breathing and during CFV. When steady-state and progressive hypercapnia were compared, the frequency and height of the MTA phrenic neurogram were independent of the rate of induction of hypercapnia during each mode of ventilation. During spontaneous ventilation, the response to hypercapnia comprised mainly an increase in frequency with only a slight increase in the amplitude of the MTA phrenic waveform. During muscular paralysis and CFV, the responses were similar to those observed after vagotomy with mainly an increase in the amplitude and only a small increase in frequency. For both spontaneous breathing and CFV, increases in frequency were achieved mainly by a shortening in expiratory time with the inspiratory time remaining relatively constant. Our data support the concept of a centrally patterned respiratory generator, whose inherent pattern is modified by phasic feedback from peripheral receptors mainly of vagal origin.     

Responses of single phrenic motoneurons to altered ventilatory drives in anesthetized dogs

We studied the effects of altered ventilatory drives on the activity of the whole phrenic nerve and single phrenic motoneurons in dogs anesthetized with alpha-chloralose and paralyzed with gallamine triethiodide. Single phrenic motoneurons were classified as either late-onset or early-onset motoneurons (LOM and EOM, respectively), depending on the time of onset of their activity during inspiration. Increase in ventilatory drive was induced by altering chemical drive with changes in arterial blood gases and also by altering the vagal afferent contribution to ventilatory drive. The latter was accomplished by inducing pulmonary gas embolism (PGE) during hyperoxia. Whole phrenic nerve activity was increased by both types of increase in ventilatory drive. In both cases, changes in the firing pattern of LOMs and EOMs were responsible for the increased phrenic output. The changes in post-PGE firing pattern of the LOMs generally consisted of a shift in the time of onset to an earlier point in inspiration and an increase in the number of spikes per inspiratory cycle. Vagotomy abolished the difference between the contributions of LOMs and EOMs to the phrenic response to PGE. Data from dogs studied while they were breathing spontaneously were qualitatively the same as those from the paralyzed animals, indicating no major role for phasic volume feedback in these responses. Our data regarding altered chemical drive are similar to those reported earlier in other species, whereas those regarding PGE demonstrate that vagally mediated increases in ventilatory drive affect both LOMs and EOMs, although LOMs are affected to a greater degree.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decrease in lung volume-related feedback enhances laryngeal reflexes to negative pressure.

Negative pressure applied to the upper airway has an excitatory effect on the activity of upper airway muscles and an inhibitory effect on thoracic inspiratory muscles. The role of lung volume feedback in this response was investigated in 10 anesthetized spontaneously breathing adult rabbits. To alter lung volume feedback, the lower airway was exposed to SO2 (250 ppm for 15 min), thereby blocking slowly adapting receptors (SARs). Negative pressure pulses (5, 10, and 20 cmH2O, 300-ms duration) were applied to the functionally isolated upper airway before and after SAR blockade. Tracheal airflow and electromyogram (EMG) of the genioglossus and alae nasi were recorded. Peak EMG, peak inspiratory flow, tidal volume, and respiratory timing of control breaths (3 breaths immediately preceding test) and test breaths were determined. Analysis of variance was used to determine the significance of the effects. Negative pressure pulses increased peak EMG of genioglossus and alae nasi and inspiratory duration and decreased peak inspiratory flow. These effects were larger after SAR blockade. We conclude that a decrease in volume feedback from the lung augments the response to upper airway pressure change.     

Dose effect of pentobarbital sodium on control of breathing in cats

The dose effect of pentobarbital sodium on integrated ("moving time average") phrenic activity (EPHR), transdiaphragmatic pressure (Pdi), gastric pressure (Pga), changes in lung volume (V), and mechanical properties of the respiratory system was studied in six cats breathing room air. Increased pentobarbital dose from an initial value of 35 mg/kg ip, had no substantial effect on the relationship between EPHR and Pdi during both unoccluded and occluded inspirations, indicating that the diaphragmatic excitation-contraction coupling was not affected. Similarly, increased anesthetic dose had no effect on the relationship between EPHR and delta Pga during both occluded and unoccluded breaths, suggesting that the contribution of the diaphragm to the breathing movements did not change with increasing depth of anesthesia. Although the time course of phrenic activity showed substantial interanimal differences, the shape of the phrenic neurogram did not change substantially with increased pentobarbital dose in any of the cats studied. Increased anesthetic dose depressed, in the same proportion, the rate of rise of EPHR, Pdi, and V, but the mechanical properties of the respiratory system remained unchanged. The depression of ventilation with increased anesthetic dose was not proportional to the drop in central inspiratory activity, as quantified in terms of rate of rise of EPHR.     

Vagal amplification of phrenic nerve activity at different levels of ventilation in spontaneously breathing cats

The vagal amplification of phrenic nerve activity (APHR) was studied as a function of minute ventilation (VE) in 12 spontaneously breathing, anaesthetized cats. Increasing levels of VE were obtained by repeated venous administrations of 2,4-dinitrophenol. The APHR was obtained from the ratio of the phrenic nerve activities in a normal and in an occluded breath. The APHR is thought to be mediated by slowly and/or rapidly adapting stretch receptors. Because airway CO2 may inhibit the discharge of these receptors, we also investigated the influence on APHR of adding 1% and 2% by volume of CO2 to inspired gas. The results showed that an increase in VE had no influence on APHR. The values of APHR ranged from 0.95 to 1.31 and were on average 1.08. Low levels of CO2 in inspired gas did not influence APHR. Our findings suggest that the vagal amplification of central inspiratory output as determined from phrenic nerve activity has a constant gain and it seems to play a relatively unimportant role in sustaining hyperpnoeic breathing.     

Cricothyroid muscle responses to increased chemical drive in awake normal humans

To examine the response of the cricothyroid muscle (CT) to increased chemical drive, we measured its electromyogram simultaneously with that of the alae nasi (AN) in seven normal awake subjects. During both progressive hyperoxic hypercapnia and hypoxia, peak integrated inspiratory activity (moving time average, MTA) of the CT and AN increased as a power function of mean inspiratory flow (ratio of tidal volume to inspiratory time, VT/TI), given by MTA = a(VT/TI)b + c (where a, b, and c are constants). The exponent b varied from 0.009 to 3.4 among subjects but was correlated between CT and AN both during hypercapnia (r = 0.86) and hypoxia (r = 0.81). The onset of inspiratory activity of the CT and AN preceded that of inspiratory flow. Expressed as a percentage of expiratory time, the CT lead time rose from 7% at rest to 20% during hyperpnea. The corresponding values for the AN were from 22 to 52% (both P less than 0.03). Thus the pattern of response of the CT and AN is similar and related to that of the inspiratory muscles in a curvilinear manner. The findings suggest that during chemical stimulation the electrical activity of the CT is analogous to that of the AN, an upper airway dilator.     

Inspiratory lung impedance in COPD: effects of PEEP and immediate impact of lung volume reduction surgery.

Frequency-dependent characteristics of lung resistance (RL) and elastance (EL) are sensitive to different patterns of airway obstruction. We used an enhanced ventilator waveform (EVW) to measure inspiratory RL and EL spectra in ventilated patients during thoracic surgery. The EVW delivers an inspiratory flow waveform with enhanced spectral excitation from 0.156 to 8.1 Hz. Estimates of the coefficients in a trigonometric approximation of the EVW flow and transpulmonary pressure inspirations yielded inspiratory RL and EL spectra. We applied the EVW in a group with mild obstruction undergoing various thoracoscopic procedures (n = 6), and another group with severe chronic obstructive pulmonary disease undergoing lung volume reduction surgery (n = 8). Measurements were made at positive end-expiratory pressure (PEEP) of 0, 3, and 6 cmH(2)O. Inspiratory RL was similar in both groups despite marked differences in spirometry. The chronic obstructive pulmonary disease patients demonstrated a pronounced frequency-dependent increase in inspiratory EL consistent with severe heterogeneous peripheral airway obstruction. PEEP appears to have beneficial effects by reducing peripheral airway resistance. Lung volume reduction surgery resulted in increased inspiratory RL and EL at all frequencies and PEEPs, possibly due to loss of diseased lung tissue, pulmonary edema, increased mechanical heterogeneity, and/or an improvement in airway tethering.     

Inhibition of inspiratory upper airway motoneuron activity by phasic volume feedback

The effects of phasic volume feedback on efferent hypoglossal, recurrent laryngeal and phrenic nerve activity were studied in decerebrate, paralyzed intubated cats ventilated with a phrenic-driven servo-respirator. The gain of the respirator was altered for single inspirations, and the resulting changes in neural activities were quantified by comparison with respective neural activities without phasic volume feedback. The volume thresholds for suppression of hypoglossal and recurrent laryngeal activities were time independent. Above these two thresholds and extending over a substantial range, volume feedback caused graded inhibition of upper airway motoneuron outputs. At any particular time during inspiration the relationships between hypoglossal or recurrent laryngeal inhibition and volume were concave to the volume axis. Rate of airflow appeared to exert an effect on upper airway motoneuron activity independent of volume. These results indicate that for hypoglossal and recurrent laryngeal efferent activity 1) volume feedback can cause a sustained graded inhibition throughout inspiration; 2) the volume thresholds are time independent; and 3) partial inhibition decreases susceptibility to additional inhibition. These actions of volume feedback on upper airway motoneuron output differ from those on phrenic efferent discharge and show that phasic vagal volume feedback has a marked and differential effect on upper airway motoneuron activity. The vagus, in this preparation, appears to play a critical role in the regulation of upper airway motoneuron activity and therefore maintenance of upper airway patency.     

Factors influencing mechanical performance of neonatal high-frequency ventilators

Factors influencing the mechanical performance of neonatal high-frequency ventilators of diverse design were assessed under controlled conditions. Each of eight ventilators was coupled to in vitro models of the neonatal respiratory system simulating disease of varying severity. The principal performance characteristics examined were frequency dependence and load dependence of tidal volume delivered, peak inspiratory flow rate, and waveforms of pressure at either end of the endotracheal tube. Despite wide diversity of ventilator designs, including jets, flow interrupters, and oscillators, common features emerged. In almost all devices tidal volume increased with endotracheal tube size, was invariant with respiratory system compliance, and decreased with frequency of oscillation. Peak inspiratory flow rates for a given tidal volume and frequency were smallest in the group of oscillators compared with jets and flow interrupters. Proximal pressure was a poor indicator of distal pressure. These findings suggest that delivered tidal volume may be sensitive to endotracheal tube size and airway patency but relatively insensitive to changes in lung tissue or chest wall mechanical properties. In these regards high-frequency ventilation differs from pressure-limited conventional mechanical ventilation. Comparison of data obtained at different clinical centers using high-frequency ventilators of varying design may be possible by taking these factors into account.     

Effects of early hypoxia on breathing pattern in rabbit pups before and after vagotomy

We examined the influence of vagal pulmonary receptors exerted on the breathing pattern and inspiratory activities of phrenic nerve and intercostal electromyograms (EMG) during hypoxia in rabbit pups. Animals in their second week of life were anaesthetized with ketamine (50 mg/kg) and acepromazine (3 mg/kg) and tracheostomized. While they breathed spontaneously, we recorded tidal volume (VT), integrated phrenic activity (PHR), integrated external intercostal EMG (INT), and blood pressure (BP). To prevent secondary ventilatory depression, animals were exposed to 12% O2 (balanced with N2) for no longer than 5 min before and after vagotomy. All measurements were taken from 1 min following the onset of hypoxic exposure until the end of the run. During hypoxia, VT, PHR, and INT increased in intact rabbit pups. There was an almost immediate decrease in BP that was maintained during the total period of hypoxia exposure. Hypoxia resulted in inconsistent changes in inspiratory (TI) and expiratory (TE) time in intact animals. Following vagotomy, PHR, INT, VT, BP, and TE responses were the same as in intact animals. However, TI significantly decreased in all animals. In response to hypoxia with and without vagal feedback, INT increased less than PHR in most cases. Qualitatively similar effects of hypoxia were observed in an adult rabbit. The results reveal that the increase in VT and the shortening of TI in response to hypoxia do not depend on vagal feedback in rabbits during the early postnatal period. In fact TI shortening was significant only without vagal feedback.