Breathing patterns during varied activities.

The level of ventilation attained and breathing patterns adopted during activity have important implications for the distribution and deposition of particles that are inhaled. However, breathing patterns and levels of ventilation adopted during specific physical activities are unknown. We used a noninvasive means of measuring ventilation in subjects performing a variety of activities (bicycling, arm ergometry, lifting, and pulling) during unencumbered (no mouthpiece) breathing and while breathing through a mouthpiece. Minute ventilation (VE), tidal volume (VT), inspiratory time (TI), and total breathing cycle time (TT) were measured initially both spirometrically and from body surface displacements. When a mouthpiece was used, VE and breathing patterns were significantly altered during all activities such that VE, VT, and TT increased by 16, 34, and 20%, respectively. This mouthpiece effect was attenuated at the higher levels of VE. A task dependency of breathing pattern was also noted such that there was much greater variability of VT and TI for a given VE during the lifting activity compared with bicycling (coefficient of variation for VT of 0.39 +/- 0.09 vs. 0.20 +/- 0.07, P less than 0.01; and for TI of 0.38 +/- 0.08 vs. 0.21 +/- 0.08, P less than 0.01). We conclude that a mouthpiece significantly alters breathing pattern during varied types and intensities of activities, and breathing patterns may differ significantly from one activity to another. When the total dose of particulates inhaled in the lung are assessed, the mouthpiece effect and activity effect on breathing pattern must be considered.     

Airway anesthesia effects on hypercapnic breathing pattern in humans

Minute ventilation (VE) and breathing pattern during an abrupt increase in fractional CO2 were compared in 10 normal subjects before and after airway anesthesia. Subjects breathed 7% CO2-93% O2 for 5 min before and after inhaling aerosolized lidocaine. As a result of airway anesthesia, VE and tidal volume (VT) were greater during hypercapnia, but there was no effect on inspiratory time (TI). Therefore, airway anesthesia produced an increase in mean inspiratory flow (VT/TI) during hypercapnia. The increase in VT/TI was compatible with an increase in neuromuscular output. There was no effect of airway anesthesia on the inspiratory timing ratio or the shape and position of the curve relating VT and TI. We also compared airway resistance (Raw), thoracic gas volume, forced vital capacity, forced expired volume at 1s, and maximum midexpiratory flow rate before and after airway anesthesia. A small (0.18 cmH2O X l-1 X s) decrease in Raw occurred after airway anesthesia that did not correlate with the effect of airway anesthesia on VT/TI. We conclude that airway receptors accessible to airway anesthesia play a role in hypercapnic VE.     

Ventilatory response to fatiguing and nonfatiguing resistive loads in awake sheep

To study the changes in ventilation induced by inspiratory flow-resistive (IFR) loads, we applied moderate and severe IFR loads in chronically instrumented and awake sheep. We measured inspired minute ventilation (VI), ventilatory pattern [inspiratory time (TI), expiratory time (TE), respiratory cycle time (TT), tidal volume (VT), mean inspiratory flow (VT/TI), and respiratory duty cycle (TI/TT)], transdiaphragmatic pressure (Pdi), functional residual capacity (FRC), blood gas tensions, and recorded diaphragmatic electromyogram. With both moderate and severe loads, Pdi, TI, and TI/TT increased, TE, TT, VT, VT/TI, and VI decreased, and hypercapnia ensued. FRC did not change significantly with moderate loads but decreased by 30-40% with severe loads. With severe loads, arterial PCO2 (PaCO2) stabilized at approximately 60 Torr within 10-15 min and rose further to levels exceeding 80 Torr when Pdi dropped. This was associated with a lengthening in TE and a decrease in breathing frequency, VI, and TI/TT. We conclude that 1) timing and volume responses to IFR loads are not sufficient to prevent alveolar hypoventilation, 2) with severe loads the considerable increase in Pdi, TI/TT, and PaCO2 may reduce respiratory muscle endurance, and 3) the changes in ventilation associated with neuromuscular fatigue occur after the drop in Pdi. We believe that these ventilatory changes are dictated by the mechanical capability of the respiratory muscles or induced by a decrease in central neural output to these muscles or both.     

Short-term potentiation of breathing in humans.

The purpose of this study was to determine if the increase in ventilation induced by hypoxic stimulation of the carotid bodies (CB) persists after cessation of the stimulus in humans. I reasoned that a short-term potentiation (STP) of breathing, sometimes called an "afterdischarge," could be unmasked by combining hypoxia with exercise, because ventilation increases synergistically under these conditions. Seven young healthy men performed mild bicycle exercise (30% peak power) while breathing O2 for 1.5 min ("control" state), and their CB were then stimulated by 1.5 min of hypoxic exercise (10% O2--balance N2). CB stimulation was then terminated by changing the inspirate back to O2 as exercise continued. Inspiratory and expiratory duration (TI and TE) and inspiratory flow and its time integral [tidal volume (VT)] were measured with a pneumotachometer. Inspired minute ventilation (VI) and mean inspiratory flow (VT/TI) declined exponentially after the cessation of CB stimulation, with first-order time constants of 28.6 +/- 6.7 and 24.6 +/- 1.6 (SD) s, respectively. The slow decay of VI was due primarily to potentiation of both TI and TE, although the effect on the latter predominated. Additional experiments in six subjects showed that brief intense CB stimulation with four to five breaths of N2 during mild exercise induced STP of similar magnitude to that observed in the hypoxic exercise experiments. Finally, the imposition of hyperoxia during air breathing exercise at a level of respiratory drive similar to that induced by the hypoxic exercise did not change VI significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human breathing patterns on mouthpiece or face mask during air, CO2, or low O2

Steady-state breathing patterns on mouthpiece and noseclip (MP) and face mask (MASK) during air and chemostimulated breathing were obtained from pneumotachometer flow. On air, all 10 subjects decreased frequency (f) and increased tidal volume (VT) on MP relative to that on MASK without changing ventilation (VE), mean inspiratory flow (VT/TI), or mean expiratory flow (VT/TE). On elevated CO2 and low O2, MP exaggerated the increase in VE, f, and VT/TE due to profoundly shortened TE. On elevated CO2, MASK exaggerated VT increase with little change in f. Increased VE and VT/TI were thus due to increased VT. During low O2 on MASK, both VT and f increased. During isocapnia, shortened TE accounted for increased f; during hypocapnia, increased f was related primarily to shortened TI. Thus the choice of a mouthpiece or face mask differentially alters breathing pattern on air and all components of ventilatory responses to chemostimuli. In addition, breathing apparatus effects are not a simple consequence of a shift from oronasal to oral breathing, since a noseclip under the mask did not change breathing pattern from that on mask alone.     

Effect of respiratory apparatus on respiration

A mouthpiece plus noseclip (MP + NC) is frequently used in performing measurements of breathing patterns. Although the effects the apparatus exerts on breathing patterns have been studied, the mechanism of the changes it causes remains unclear. The current study examines the effects on respiratory patterns of a standard (17-mm-diam) MP + NC during room air (RA) breathing and the administration of 2 and 4% CO2 in normal volunteers and in patients 2-4 days after abdominal operation. When compared with values obtained with a noninvasive canopy system, the MP + NC induced increases in minute ventilation (VE), tidal volume (VT), and mean inspiratory flow (VT/TI), but not frequency (f) or inspiratory duty cycle, during both RA and CO2 administration. The percentage increase in VE, VT, and VT/TI caused by the MP + NC decreased as the concentration of CO2 increased. During RA breathing, the application of noseclip alone resulted in a decrease in f and an increase in VT, but VE and VT/TI were unchanged. The changes were attenuated during the administration of 2 and 4% CO2. Reducing the diameter of the mouthpiece to 9 mm abolished the alterations in breathing pattern observed with the larger (17-mm) diameter MP.     

Frequency and amplitude effects during high-frequency vibration ventilation in dogs

High-frequency external body vibration, combined with constant gas flow at the tracheal carina, was previously shown to be an effective method of ventilation in normal dogs. The effects of frequency (f) and amplitude of the vibration were investigated in the present study. Eleven anesthetized and paralyzed dogs were placed on a vibrating table (4-32 Hz). O2 was delivered near the tracheal carina at 0.51.kg-1.min-1, while mean airway pressure was kept at 2.4 +/- 0.9 cmH2O. Table vertical displacement (D) and acceleration (a), esophageal (Pes), and tracheal (Ptr) peak-to-peak pressures, and tidal volume (VT) were measured as estimates of the input amplitude applied to the animal. Steady-state arterial PCO2 (PaCO2) and arterial PO2 (PaO2) values were used to monitor overall gas exchange. Typically, eucapnia was achieved with f greater than 16 Hz, D = 1 mm, a = 1 G, Pes = Ptr = 4 +/- 2 cmH2O, and VT less than 2 ml. Inverse exponential relationships were found between PaCO2 and f, a, Pes, and Ptr (exponents: -0.69, -0.38, -0.48, and -0.54, respectively); PaCO2 decreased linearly with increased displacement or VT at a fixed frequency (17 +/- 1 Hz). PaO2 was independent of both f and D (393 +/- 78 Torr, mean +/- SD). These data demonstrate the very small VT, Ptr, and Pes associated with vibration ventilation. It is clear, however, that mechanisms other then those described for conventional ventilation and high-frequency ventilation must be evoked to explain our data. One such possible mechanism is forcing of flow oscillation between lung regions (i.e., forced pendelluft).     

Heart rate and breathing pattern: interactions and sex differences

Ten subjects (five males, five females) were studied in resting conditions. Ventilation (VT, f, TI, TE), heart rate (HR) and RR interval were recorded or measured. Each subject voluntarily breathed with spontaneous frequency at different ratios of his spontaneous tidal volume (VrT). The results show that sinus arrhythmia increases with lung volume but without effect on mean heart rate. When VT is increased by two times its spontaneous value, the ventilatory drive (VT/TI) is raised in both sexes; the relative duration of inspiration (TI/Ttot) is modified (+20%) in females only. Thus with the cardiac effects of increasing lung volume being similar in both sexes, we conclude that sinus arrhythmia is not generated by sensory inputs from pulmonary structures, but that its origin is at the CNS level. Moreover, there may be a sex difference in the control of voluntary ventilation, a suggestion requiring further investigation.     

The pattern of breathing during hypoxic exercise

Breathing pattern was studied in six subjects in normoxia (FIO2 = 0.21) and hypoxia (FIO2 = 0.12) at rest and during incremental work-rate exercise. Ventilation (V) as well as mean inspiratory flow (VT/TI) increased with exercise intensity and were augmented in the hypoxic environment, whereas the ratio between inspiratory (TI) and total (Ttot) breath durations increased with exercise intensity but was unaffected by hypoxia. The relationship of tidal volume (VT) and inspiratory time duration (TI) showed linear, coinciding ranges for the normoxic and hypoxic conditions up to VT/TI values of about 2.5 1.s-1. At higher VT/TI values TI continued to decrease, whereas VT tended to level off, an effect which was more evident in the hypoxic condition. The results suggest that the hypoxic augmentation of exercise hyperpnea is primarily brought about by an enhancement of central inspiratory drive, the timing component being largely unaffected by the hypoxic environment, and that at low to moderate levels of exercise hyperpnea inspiratory off-switch mechanisms are essentially unaffected by moderate hypoxia.     

Carbon dioxide effects on the ventilatory response to sustained hypoxia

We examined the interrelation between CO2 and the ventilatory response to moderate (80% arterial saturation) sustained hypoxia in normal young adults. On a background of continuous CO2-stimulated hyperventilation, hypoxia was introduced and sustained for 25 min. Initially, with the introduction of hypoxia onto hypercapnia, there was a brisk additional increase in inspiratory minute ventilation (VI) to 284% of resting VI, but the response was not sustained and hypoxic VI declined by 36% to a level intermediate between the initial increase and the preexisting hypercapnic hyperventilation. Through the continuous hypercapnia, the changes in hypoxic ventilation resulted from significant alterations in tidal volume (VT) and mean inspiratory flow (VT/TI) without changes in respiratory timing. In another experiment, sustained hypoxia was introduced on the usual background of room air, either with isocapnia or without maintenance of end-tidal CO2 (ETCO2) (poikilocapnic hypoxia). Regardless of the degree of maintenance of ETCO2, during 25 min of sustained hypoxia, VI showed an initial brisk increase and then declined by 35-40% of resting VI to a level intermediate between the initial response and resting room air VI. For both isocapnia and poikilocapnic conditions, the attenuation of VI was an expression of a diminished VT. Thus the decline in ventilation with sustained hypoxia occurred regardless of the background ETCO2, suggesting that the mechanism underlying the hypoxic decline is independent of CO2.     

Distribution of airway narrowing during hyperpnea-induced bronchoconstriction in guinea pigs

Increasing minute ventilation of dry gas shifts the principal burden of respiratory heat and water losses from more proximal airway to airways farther into the lung. If these local thermal transfers determine the local stimulus for bronchoconstriction, then increasing minute ventilation of dry gas might also extend the zone of airway narrowing farther into the lung during hyperpnea-induced bronchoconstriction (HIB). We tested this hypothesis by comparing tantalum bronchograms in tracheostomized guinea pigs before and during bronchoconstriction induced by dry gas hyperpnea, intravenous methacholine, and intravenous capsaicin. In eight animals subjected to 5 min of dry gas isocapnic hyperpnea [tidal volume (VT) = 2-5 ml, 150 breaths/min], there was little change in the diameter of the trachea or the main stem bronchi up to 0.75 cm past the main carina (zone 1). In contrast, bronchi from 0.75 to 1.50 cm past the main carina (zone 2) narrowed progressively at all minute ventilations greater than or equal to 300 ml/min (VT = 2 ml). More distal bronchi (1.50-3.10 cm past the main carina; zone 3) did not narrow significantly until minute ventilation was raised to 450 ml/min (VT = 3 ml). The estimated VT during hyperpnea needed to elicit a 50% reduction in airway diameter was significantly higher in zone 3 bronchi [4.3 +/- 0.8 (SD) ml] than in zone 2 bronchi (3.5 +/- 1.1 ml, P less than 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory depression produced by centrally administered taurine in the cat

The effects of taurine (0.8-64.8 mumol) were studied on respiratory activity following intracisternal (cisterna magna) and intracerebroventricular (lateral ventricle) injections in cats anesthetized with alpha-chloralose. Respiratory activity was measured by using a Fleisch pneumotachograph and monitoring tracheal airflow. The flow signal was integrated to obtain tidal volume (VT) and respiratory rate (f) was obtained by counting the number of VT excursions over one minute. Inspiratory (TI), expiratory (TE) and total (TTOT) cycle durations were also determined during this time period. In addition, end-tidal CO2 was continuously monitored. Associated changes in arterial pressure (femoral artery cannula) and heart rate were also determined. After injections into the cisterna magna, taurine caused dose-related decreases in minute ventilation (VE). The maximal decrease in VE was from 495 +/- 59 to 64 +/- 14 ml/min (p less than 0.05), and was due to both decreases in VT (from 27 +/- 3 to 5 +/- 1 ml; p less than 0.05) and f (from 18 +/- 1 to 12 +/- 2 breaths/min; p less than 0.05). TE and TTOT were increased from 2.4 +/- 0.4 to 4.5 +/- 0.6 sec (p less than 0.05) and from 3.7 +/- 0.4 to 6.4 +/- 0.8 sec (p less than 0.05), respectively. Mean inspiratory flow (VT/TI), a measure of inspiratory drive, was decreased from 21 +/- 4 to 4 +/- 2 ml/sec (p less than 0.05). Apnea occurred in 5 of 6 animals after the 64.8 mumol dose. This respiratory depression occurred without any significant change in arterial pressure. After lateral ventricle injections, taurine also caused dose-related, but not as pronounced, decreases in respiratory activity. In addition, taurine caused significant decreases (p less than 0.05) in arterial pressure in doses that decreased VE. Taurine administered intravenously had no significant cardiorespiratory depressant effects. These data indicate that centrally administered taurine produces respiratory depression and, depending on the route of CNS administration, also produces hypotension.     

Role of expiratory flow limitation in determining lung volumes and ventilation during exercise.

We determined the role of expiratory flow limitation (EFL) on the ventilatory response to heavy exercise in six trained male cyclists [maximal O2 uptake = 65 +/- 8 (range 55-74) ml. kg-1. min-1] with normal lung function. Each subject completed four progressive cycle ergometer tests to exhaustion in random order: two trials while breathing N2O2 (26% O2-balance N2), one with and one without added dead space, and two trials while breathing HeO2 (26% O2-balance He), one with and one without added dead space. EFL was defined by the proximity of the tidal to the maximal flow-volume loop. With N2O2 during heavy and maximal exercise, 1) EFL was present in all six subjects during heavy [19 +/- 2% of tidal volume (VT) intersected the maximal flow-volume loop] and maximal exercise (43 +/- 8% of VT), 2) the slopes of the ventilation (DeltaVE) and peak esophageal pressure responses to added dead space (e.g., DeltaVE/DeltaPETCO2, where PETCO2 is end-tidal PCO2) were reduced relative to submaximal exercise, 3) end-expiratory lung volume (EELV) increased and end-inspiratory lung volume reached a plateau at 88-91% of total lung capacity, and 4) VT reached a plateau and then fell as work rate increased. With HeO2 (compared with N2O2) breathing during heavy and maximal exercise, 1) HeO2 increased maximal flow rates (from 20 to 38%) throughout the range of vital capacity, which reduced EFL in all subjects during tidal breathing, 2) the gains of the ventilatory and inspiratory esophageal pressure responses to added dead space increased over those during room air breathing and were similar at all exercise intensities, 3) EELV was lower and end-inspiratory lung volume remained near 90% of total lung capacity, and 4) VT was increased relative to room air breathing. We conclude that EFL or even impending EFL during heavy and maximal exercise and with added dead space in fit subjects causes EELV to increase, reduces the VT, and constrains the increase in respiratory motor output and ventilation.     

Barometric measurement of tidal volume: effects of pattern and nasal temperature

The accuracy of the formula derived by Drorbaugh and Fenn (Pediatrics 16: 81-86, 1955) for calculating tidal volume (VT) from the phasic pressure change measured when an animal breathes in a closed chamber has recently been challenged. Epstein and Epstein (Respir. Physiol. 32: 105-120, 1978) argue that the formula may underestimate VT by up to 30% and predict that the error increases as the ratio of inspiratory duration (TI) to total breath duration (Ttot) increases, and as the expired temperature at the nares (TN) increases. To test their theory, I measured VT in anesthetized rats by the barometric technique and by conventional pneumotachography simultaneously. TN was varied from ambient to body temperature by passing a variable current through the pneumotachograph heater; TI/Ttot was varied by changing FICO2 and by selecting different rats. The predictions were confirmed. A factor is derived for retrospectively correcting VT estimated by the Drorbaugh-Fenn formula. It requires knowledge of TN and TI/Ttot and reduces the error between experiments to under 20% and within each experiment to about 5%. To facilitate its use, TN was measured in rat, rabbit, cat, man, and infant pigtail monkey.     

Respiratory adaptations to dead space loading during maximal incremental exercise

We examined the effects of dead space (VD) loading on breathing pattern during maximal incremental exercise in eight normal subjects. Addition of external VD was associated with a significant increase in tidal volume (VT) and decrease in respiratory frequency (f) at moderate and high levels of ventilation (VI); at a VI of 120 l/min, VT and f with added VD were 3.31 +/- 0.33 liters and 36.7 +/- 6.7 breaths/min, respectively, compared with 2.90 +/- 0.29 liters and 41.8 +/- 7.3 breaths/min without added VD. Because breathing pattern does not change with CO2 inhalation during heavy exercise (Gallagher et al. J. Appl. Physiol. 63: 238-244, 1987), the breathing pattern response to added VD is probably a consequence of alteration in the PCO2 time profile, possibly sensed by the carotid body and/or airway-pulmonary chemoreceptors. The increase in VT during heavy exercise with VD loading indicates that the tachypneic breathing pattern of heavy exercise is not due to mechanical limitation of maximum ventilatory capacity at high levels of VT.     

Variability of resting respiratory drive and timing in healthy subjects

Studies of breathing pattern have focused primarily on changes in the mean values of the breathing pattern components, whereas there has been minimal investigation of breath-to-breath variability, which should provide information on the constancy with which respiration is controlled. In this study we examined the variability of breathing pattern both on a breath-to-breath and day-to-day basis by calculating the coefficient of variation (i.e., the standard deviation expressed as a percentage of the mean). By examining breath-to-breath data, we found that the coefficients of variation of tidal volume (VT) and fractional inspiratory time (TI/TT, an index of timing) obtained with an inductive plethysmograph and spirometer were within 1% of each other. Examination of breath-to-breath variability in breathing pattern over a 15-min period in 65 subjects revealed large coefficients of variation, indicating the need to base calculations on a relatively large number of breaths. Less breath-to-breath variability was observed in respiratory frequency [f, 20.8 +/- 11.5% (SD)] and TI/TT (17.9 +/- 6.5%) than in VT (33 +/- 14.9%) and mean inspiratory flow (VT/TI, an index of drive; 31.6 +/- 12.6%; P less than 0.0001). Older subjects (60-81 yr) displayed greater breath-to-breath variability than young subjects (21-50 yr). Use of a mouthpiece did not affect the degree of variability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human breathing pattern responses to loading with increased background impedance

We determined the influence of the background level of mechanical impedance on the respiratory responses to very small mechanical loads, at or below the threshold for conscious perception. We used a pseudorandom load application technique to estimate the immediate pattern responses from the zeroth lag of the cross correlation between the load application sequence and the respiratory pattern components of tidal volume (VT), inspiratory and expiratory time (TI and TE), and the instantaneous respiratory frequency (f), minute ventilation (VI), and mean inspiratory flow (VT/TI). Elevation of the background resistance served to reduce the TI and TE responses to small perturbations in resistance from those in the control background state, which resulted in generally smaller perturbations of f, VI, and VT/TI. Elevation of the background elastance, however, served to initiate a TI reduction not seen in the control state but did not appreciably affect the rest of the pattern responses to the load perturbations. Thus the neural reflexes involved in breath-by-breath pattern regulation are modulated by the background level of the respiratory impedance, as well as by the type and size of the load perturbation.     

Effects of acute hyperbaric oxygenation on respiratory control in cats

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.     

Ventilatory effects and interactions with change in PaO2 in awake goats.

We utilized selective carotid body (CB) perfusion while changing inspired O2 fraction in arterial isocapnia to characterize the non-CB chemoreceptor ventilatory response to changes in arterial PO2 (PaO2) in awake goats and to define the effect of varying levels of CB PO2 on this response. Systemic hyperoxia (PaO2 greater than 400 Torr) significantly increased inspired ventilation (VI) and tidal volume (VT) in goats during CB normoxia, and systemic hypoxia (PaO2 = 29 Torr) significantly increased VI and respiratory frequency in these goats. CB hypoxia (CB PO2 = 34 Torr) in systemic normoxia significantly increased VI, VT, and VT/TI; the ventilatory effects of CB hypoxia were not significantly altered by varying systemic PaO2. We conclude that ventilation is stimulated by systemic hypoxia and hyperoxia in CB normoxia and that this ventilatory response to changes in systemic O2 affects the CB O2 response in an additive manner.     

Sleep and maturation of eucapnic ventilation and CO2 sensitivity in the premature primate

The effects of sleep state and postnatal maturation on steady-state CO2 sensitivity, "inspiratory drive" (VT/TI), and the inspiratory "duty cycle" (TI/Ttot) were examined in nine unanesthetized premature Macaca nemestrina in the first 3 wk of life. Minute volume (VE) in room air was less in NREM sleep than in the awake state but there were no differences in VE, VT/TI, or TI/Ttot between REM and NREM sleep. VE and VT/TI corrected for body weight increased in REM and NREM sleep with postnatal maturation whereas TI/Ttot did not vary. Concomitant with this increase in room air VE and VT/TI, an increase in CO2 sensitivity (delta V/delta Paco2) with postnatal maturation was documented in NREM sleep. CO2 sensitivity was similar between REM and NREM states at each postnatal age. The increase in VE following inhalation of 2-5% CO2 was mediated by an increase in VT/TI, whereas TI/Ttot remained constant. The differences in the effect of sleep on CO2 sensitivity between neonates and adults are discussed and possible mechanisms for the observed developmental increase in CO2 sensitivity are proposed.