Lung mechanics and neuromuscular output during CO2 inhalation after airway anesthesia

Airway anesthesia with aerosolized lidocaine has been associated with an increase in minute ventilation (VE) during CO2 inhalation. The increase in VE may be due to increased neuromuscular output or decreased mechanical load on breathing. To evaluate this we measured VE, breathing pattern, mouth occlusion pressure, and lung mechanics in 20 normal subjects during room-air breathing and then inhalation of 6% CO2-94% O2, before and after airway anesthesia. Measurements of lung mechanics included whole-lung resistance, dynamic and static compliance, and functional residual capacity. Airway anesthesia had no detectable effect on any measurements during room-air breathing. During CO2 inhalation, airway anesthesia produced increases in VE and mean inspiratory flow rate (VT/TI) and more negative inspiratory pleural pressure but had no detectable effect on lung mechanics or mouth occlusion pressure. Pleural pressure was more negative during the latter 25% of inspiration. We concluded that airway receptors accessible to airway anesthesia play a role in determining neuromuscular output during CO2 inhalation.     

Ventilatory response during CO2 inhalation after airway anesthesia with lidocaine

Airway anesthesia with inhaled aerosolized lidocaine has been associated with increases in minute ventilation (VE) and mean inspiratory flow rate (VT/TI) during CO2 inhalation. However, it is unclear whether these increases are local effects of the anesthesia or systemic effects of absorbed and circulating lidocaine. To evaluate this 20 normal subjects were treated on separate days with aerosolized lidocaine, intravenous lidocaine, aerosolized control solution, or intravenous control solution, and the effects of each treatment on VE and VT/TI were determined and compared during room-air breathing and inhalation of 5% CO2-95% O2. None of the treatments altered VE or VT/TI during room-air breathing. Aerosolized lidocaine produced small (5.9-6.0%) increases in VE and VT/TI during CO2 inhalation, but these effects were not present after intravenous lidocaine despite equivalent lidocaine blood levels. We concluded that the increases in VE and VT/TI after aerosolized lidocaine were local effects of airway anesthesia rather than systemic effects of absorbed and circulating lidocaine.     

Ventilatory response to high-frequency airway oscillation in humans

To investigate respiratory control during high-frequency oscillation (HFO), ventilation was monitored in conscious humans by respiratory inductive plethysmography during application at the mouth of high-frequency pressure oscillations. Studies were conducted before and after airway and pharyngeal anesthesia. During HFO, breathing became slow and deep with an increase in tidal volume (VT) of 37% (P less than 0.01) and inspiratory duration (TI) of 34% (P less than 0.01). Timing ratio (TI/TT) increased 14% (P less than 0.05) and respiratory frequency (f) decreased 12% (P less than 0.01). Mean inspiratory flow (VT/TI) did not change during HFO. Following airway anesthesia, VT increased only 26% during HFO (P less than 0.01), whereas significant changes in TI, TI/TT, and f were not observed. Pharyngeal anesthesia failed to diminish the effect of HFO on TI, TT, or f, although the increase in VT was reduced. These results indicate that 1) HFO presented in this manner alters inspiratory timing without affecting the level of inspiratory activity, and 2) receptors in the larynx and/or lower airways may in part mediate the response.     

Effects of inspiratory resistive load on respiratory control in hypercapnia and exercise

Eight healthy young men underwent two separate steady-state incremental exercise runs within the aerobic range on a treadmill with alternating periods of breathing with no load (NL) and with an inspiratory resistive load (IRL) of approximately 12 cmH2O.1-1.s. End-tidal PCO2 was maintained constant throughout each run at the eucapnic or a constant hypercapnic level by adding 0-5% CO2 to the inspired O2. Hypercapnia caused a steepening, as well as upward shift, relative to the corresponding eucapnic ventilation-CO2 output (VE - VCO2) relationship in NL and IRL. Compared with NL, the VE - VCO2 slope was depressed by IRL, more so in hypercapnic [-19.0 +/- 3.4 (SE) %] than in eucapnic exercise (-6.0 +/- 2.0%), despite a similar increase in the slope of the occlusion pressure at 100 ms - VCO2 (P100 - VCO2) relationship under both conditions. The steady-state hypercapnic ventilatory response at rest was markedly depressed by IRL (-22.6 +/- 7.5%), with little increase in P100 response. For a given inspiratory load, breathing pattern responses to separate or combined hypercapnia and exercise were similar. During IRL, VE was achieved by a greater tidal volume (VT) and inspiratory duty cycle (TI/TT) along with a lower mean inspiratory flow (VT/TI). The increase in TI/TT was solely because of a prolongation of inspiratory time (TI) with little change in expiratory duration for any given VT. The ventilatory and breathing pattern responses to IRL during CO2 inhalation and exercise are in favor of conservation of respiratory work.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Dose effect of caffeine on control of breathing and respiratory response to CO2 in cats

The dose effect of caffeine (10-70 mg/kg iv) on pulmonary ventilation (VE), mean inspiratory flow (VT/TI), and tracheal pressure generated 0.3 and 0.5 s (P0.3 and P0.5, respectively) after the onset of inspiration against airway occluded at end expiration was studied in cats anesthetized with pentobarbital sodium (35 mg/kg ip) breathing various gas mixtures. With air and 50% O2 (balance N2), increasing doses of caffeine caused a progressive increase in VE that was associated with a reduction in end-tidal PCO2. When the latter was maintained at control (precaffeine) level by inhalation of CO2, the increase in VE was, at all caffeine levels, about three times that under nonisocapnic conditions. Both under isocapnic and nonisocapnic conditions the greatest incremental changes of VE were observed after administration of the first 10-mg/kg aliquot of caffeine, i.e., the current acceptable clinical dose. In all instances, the changes in VE were proportionally the same as the corresponding changes in VT/TI, P0.3, and P0.5, suggesting that caffeine did not appreciably alter either the shape of the inspiratory driving pressure waveform or the impedance of the respiratory system but simply acted by increasing the amplitude of the neuromuscular inspiratory output. An additive interaction between caffeine and end-tidal PCO2 was observed in the VE, VT/TI, and P0.3 responses at levels of CO2 at or below the eucapnic range.     

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.     

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 hilar nerve denervation on breathing and arterial PCO2 during CO2 inhalation

We determined the effects of denervating the hilar branches (HND) of the vagus nerves on breathing and arterial PCO2 (PaCO2) in awake ponies during eupnea and when inspired PCO2 (PICO2) was increased to 14, 28, and 42 Torr. In five carotid chemoreceptor-intact ponies, breathing frequency (f) was less, whereas tidal volume (VT), inspiratory time (TI), and ratio of TI to total cycle time (TT) were greater 2-4 wk after HND than before HND. HND per se did not significantly affect PaCO2 at any level of PICO2, and the minute ventilation (VE)-PaCO2 response curve was not significantly altered by HND. Finally, the attenuation of a thermal tachypnea by elevated PICO2 was not altered by HND. Accordingly, in carotid chemoreceptor-intact ponies, the only HND effect on breathing was the change in pattern classically observed with attenuated lung volume feedback. There was no evidence suggestive of a PCO2-H+ sensory mechanism influencing VE, f, VT, or PaCO2. In ponies that had the carotid chemoreceptors denervated (CBD) 3 yr earlier, HND also decreased f, increased VT, TI, and TT, but did not alter the slope of the VE-PaCO2 response curve. However, at all levels of elevated PICO2, the arterial hypercapnia that had persistently been attenuated, since CBD was restored to normal by HND. The data suggest that during CO2 inhalation in CBD ponies a hilar-innervated mechanism influences PaCO2 by reducing physiological dead space to increase alveolar ventilation.     

Breathing pattern and CO2 response in newborn rats before and during anesthesia

We have studied the breathing pattern (minute ventilation VE, tidal volume VT, and respiratory rate f) in newborn rats before and during barbiturate (20-30 mg/kg ip) or ketamine anesthesia (40-80 mg/kg ip). Animals were intact and prone in a flow plethysmograph in thermoneutral conditions. Before anesthesia, CO2 breathing (5 min in 5% and 5 min in 10% CO2 in O2) resulted in a substantial increase in VE (169 and 208%, respectively), which was maintained throughout the entire CO2 breathing period. This indicates that, despite the extremely large VE per kilogram at rest, in these small animals there is still a large reserve for a sustained increase in VE. During barbiturate, the resting VE dropped to 45% of control, due to a reduction in VT (83%) and f (59%). This latter result was due to a prolongation of the expiratory time (214%) with no significant changes in inspiratory time. CO2 response was also much depressed, to approximately 63% of the control. The late portion of the expiratory flow-volume curves, the slope of which represents the expiratory time constant of the system, was similar before and during anesthesia in approximately 50% of the animals, whereas it increased during anesthesia in the remaining animals. Although compliance of the respiratory system was generally unaltered, the increased impedance during anesthesia probably reflected an increased resistance. Qualitatively similar results were obtained during ketamine anesthesia. Therefore, as observed in adult mammals, anesthesia in newborn rats has a marked depressant effect on resting breathing pattern and CO2 response, occasionally accompanied by an increase in the expiratory impedance of the respiratory system.     

Lack of effect of airway anesthesia on hypoxic ventilation

Airway anesthesia causes an increase in ventilation (VE) during hypercapnia. However, it is unclear if that is related to an effect of the anesthesia on all forms of stimulated V.E or just hypercapnic VE. After airway anesthesia, an increase in hypoxic VE would suggest the former, whereas absence of an increase would suggest the latter. Thus we compared VE before and after airway anesthesia during hypoxic VE. Normal subjects performed hypoxic rebreathing plus additional periods of sham hyperoxic rebreathing. There was no effect of airway anesthesia on the slope of the line relating VE and arterial O2 saturation. However, there was an upward shift in the line, attributable to an effect of anesthesia on hypercapnic VE present during rebreathing. Additional normal subjects performed eucapnic hypoxic breathing, and there was no effect of airway anesthesia on VE. We conclude that airway anesthesia has little or no effect on hypoxic VE. To date, only hypercapnic VE has been shown to be increased after airway anesthesia.     

Effects of airway anesthesia on ventilatory responses to graded dead spaces and CO2

Ventilatory response to graded external dead space (0.5, 1.0, 2.0, and 2.5 liters) with hyperoxia and CO2 steady-state inhalation (3, 5, 7, and 8% CO2 in O2) was studied before and after 4% lidocaine aerosol inhalation in nine healthy males. The mean ventilatory response (delta VE/delta PETCO2, where VE is minute ventilation and PETCO2 is end-tidal PCO2) to graded dead space before airway anesthesia was 10.2 +/- 4.6 (SD) l.min-1.Torr-1, which was significantly greater than the steady-state CO2 response (1.4 +/- 0.6 l.min-1.Torr-1, P less than 0.001). Dead-space loading produced greater oscillation in airway PCO2 than did CO2 gas loading. After airway anesthesia, ventilatory response to graded dead space decreased significantly, to 2.1 +/- 0.6 l.min-1.Torr-1 (P less than 0.01) but was still greater than that to CO2. The response to CO2 did not significantly differ (1.3 +/- 0.5 l.min-1.Torr-1). Tidal volume, mean inspiratory flow, respiratory frequency, inspiratory time, and expiratory time during dead-space breathing were also depressed after airway anesthesia, particularly during large dead-space loading. On the other hand, during CO2 inhalation, these respiratory variables did not significantly differ before and after airway anesthesia. These results suggest that in conscious humans vagal airway receptors play a role in the ventilatory response to graded dead space and control of the breathing pattern during dead-space loading by detecting the oscillation in airway PCO2. These receptors do not appear to contribute to the ventilatory response to inhaled CO2.     

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.     

Effects of hypercapnia on Breuer-Hering threshold for inspiratory termination

The effects of CO2 concentration on the timing of inspiratory duration (TI) and expiratory duration (TE) and the responses to lung inflation were studied in decerebrate paralyzed cats. With lung volume held at functional residual capacity during the breath cycle, hypercapnia (fractional concentration of inspired CO2 = 0.04) caused variable changes in TI and significant increases in TE. To obtain the Breuer-Hering threshold relationship [tidal volume (VT) vs. TI] and the timing relationship between TE and the preceding TI (TE vs. TI), ramp inflations of various sizes were used to terminate inspiration at different times in the breath cycle. Hypercapnia caused the VT vs. TI curves to shift in an upward direction so that at higher lung volumes TI was lengthened. Also, the slope of the TE vs. TI relationship was increased. The results suggest that hypercapnia diminished the sensitivity of the Breuer-Hering reflex to the lung volume, thus allowing volume to increase with little effect on TI. In addition, TE appears to become more sensitive to changes in the preceding TI. A model is presented which provides a possible neural mechanism for these responses.     

Effects of sleep-induced increases in upper airway resistance on ventilation

To determine the effects of the sleep-induced increases in upper airway resistance on ventilatory output, we studied five subjects who were habitual snorers but otherwise normal while awake (AW) and during non-rapid-eye-movement (NREM) sleep under the following conditions: 1) stage 2, low-resistance sleep (LRS); 2) stage 3-4, high-resistance sleep (HRS) (snoring); 3) with continuous positive airway pressure (CPAP); 4) CPAP + end-tidal CO2 partial pressure (PETCO2) mode isocapnic to LRS; and 5) CPAP + PETCO2 isocapnic to HRS. We measured ventilatory output via pneumotachograph in the nasal mask, PETCO2, esophageal pressure, inspiratory and expiratory resistance (RL,I and RL,E). Changes in PETCO2 were confirmed with PCO2 measurements in arterialized venous blood in all conditions in one subject. During wakefulness, pulmonary resistance (RL) remained constant throughout inspiration, whereas in stage 2 and especially in stage 3-4 NREM sleep, RL rose markedly throughout inspiration. Expired minute ventilation (VE) decreased by 12% in HRS, and PETCO2 increased in LRS (3.3 Torr) and HRS (4.9 Torr). CPAP decreased RL,I to AW levels and increased end-expiratory lung volume 0.25-0.93 liter. Tidal volume (VT) and mean inspiratory flow rate (VT/TI) increased significantly with CPAP. Inspiratory time (TI) shortened, and PETCO2 decreased 3.6 Torr but remained 1.3 Torr above AW. During CPAP (RL,I equal to AW), with PETCO2 returned to the level of LRS, VT/TI and VE were 83 and 52% higher than during LRS alone. Also on CPAP, with PETCO2 made equal to HRS, VT, VT/TI, and VE were 67, 112, and 67% higher than during HRS alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inspiratory timing of heart-lung transplant recipients during progressive hypercapnia.

The relationship between tidal volume (VT) and inspiratory duration (TI) displays biphasic characteristics during progressive hypercapnia in humans: an initial phase in which VT increases while TI remains constant (region I) and a subsequent phase with reciprocal decreases of TI as VT continues to increase (region II). Region II behavior is generally attributed, albeit inferentially, to lung volume-mediated inflation inhibition (Breuer-Hering reflex). To investigate this phenomenon, we compared CO2 responses of 10 heart-lung transplant recipients (HL) with normal pulmonary function tests and 13 normal controls. Despite pulmonary denervation, the HL exhibited region II behavior identical to controls. In four additional HL with pulmonary restriction, there were comparative decreases of the region II slope (P less than 0.05), but the absolute VT where the phase change between regions occurred was indistinguishable from the other groups. We conclude that TI shortening in humans during progressive hypercapnia occurs in the absence of pulmonary reflexes. The consistency of the VT associated with phase changes, despite pulmonary denervation, suggests that the stimulus for this behavior is volume displacement of extra-pulmonary respiratory structures.     

Postnatal maturation of ventilation and breathing pattern in kittens: influence of sleep

Ventilation and breathing pattern were studied in kittens at 1, 2, 3, 4, and 8 wk of life during quiet wakefulness (W), quiet sleep (QS), and active sleep (AS) with the barometric method. Tidal volume (VT), respiratory frequency (f), ventilation (VE), inspiratory time (TI), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory "duty cycle" (TI/TT) were measured. VT, VE, TI, TE, and VT/TI increased; f decreased and TI/TT remained constant during postnatal development in wakefulness and in both sleep states. No significant difference was observed between AS and QS for all the ventilatory parameters except TI/TT, which was greater in QS than in AS at 2 wk. VE was larger in W than in both AS and QS at all ages. This was mainly due to a greater f, TI/TT remaining constant. VT/TI, which represents an index of the central inspiratory activity, was larger in W than in sleep, VT not being significantly different whatever the stage of consciousness. The results of this study show that in the kitten 1) unlike in the adult cat, ventilation and breathing pattern are similar in QS and in AS; 2) in sleep, the central inspiratory drive appears to be independent of the type of sleep; and 3) in wakefulness, the increase of the central inspiratory activity could be related to important excitatory inputs.     

An evaluation of ventilation in dystrophic Syrian hamsters

Ventilatory responses of 10 control and 10 dystrophic male hamsters to air, hypercapnia, and hypoxia were evaluated at four ages (40, 70, 100, and 140 days). Tidal volume (VT), frequency (f), minute ventilation (VE) as well as inspiratory and expiratory time of awake animals were measured with a plethysmograph. There was a small increase of VT in both groups with age. Although there was no change of f in the control group with age, there was a progressive decrease in f (means +/- SE: 92 +/- 8, 97 +/- 9, 74.5 +/- 10, and 68 +/- 8 breaths/min) in the dystrophic group. Consequently VE on air decreased in the dystrophic group. Both groups showed similar responses to hypoxia (13 and 10% O2) and hypercapnia (3, 5, and 8% CO2) at 40 days. By 70 days the hypercapnic, but not hypoxic, response of the dystrophic animals was significantly decreased compared with that of the control group (at 8% CO2, VE = 47.4 +/- 4.1 vs. 75.7 +/- 7.6 ml/min, P less than 0.01). At both 100 and 140 days the response of the dystrophic group to CO2 was flat; i.e., the slope VE vs. fractional concentration of inspired CO2 was close to zero, and the hypoxic responses were greatly diminished. Because hamsters increase VE in response to CO2 primarily by increasing VT, the data suggest that dystrophic hamsters are unable to increase VT at a very early age, presumably due to muscle weakness. The normal response of hamsters to hypoxia, which is primarily to increase f, appears to be maintained for a longer time.     

Effect of mechanical loading on expiratory and inspiratory muscle activity during NREM sleep

We investigated the effect of acute and sustained inspiratory resistive loading (IRL) on the activity of expiratory abdominal muscles (EMGab) and the diaphragm (EMGdi) and on ventilation during wakefulness and non-rapid-eye-movement (NREM) sleep in healthy subjects. EMGdi and EMGab were measured with esophageal and transcutaneous electrodes, respectively. During wakefulness, EMGdi increased in response to acute loading (18 cmH2O.l-1.s) (+23%); this was accompanied by preservation of tidal volume (VT) and minute ventilation (VE). During NREM sleep, no augmentation was noted in EMGdi or EMGab. Inspiratory time (TI) was prolonged (+5%), but this was not sufficient to prevent a decrease in both VT and VE (-21 and -20%, respectively). During sustained loading (12 cmH2O.l-1 s) in NREM sleep, control breaths (C) were compared with the steady-state loaded breaths (SS) defined by breaths 41-50. Steady-state IRL was associated with augmentation of EMGdi (12%) and EMGab (50%). VT returned to control levels, expiratory time shortened, and breathing frequency increased. The net result was the increase in VE above control levels (+5%, P less than 0.01). No change was noted in end-tidal CO2 or O2. We concluded that 1) wakefulness is a prerequisite for immediate load compensation (in its absence, TI prolongation is the only compensatory response) and 2) during sustained IRL, the augmentation of EMGdi and EMGab can lead to complete ventilatory recovery without measurable changes in chemical stimuli.     

Influence of respiratory drive on upper airway resistance in normal men

The variations in nasal and pharyngeal resistance induced by changes in the central inspiratory drive were studied in 10 normal men. To calculate resistances we measured upper airway pressures with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other in the posterior nasopharynx, and we measured flow with a Fleisch no. 3 pneumotachograph connected to a tightly fitting mask. Both resistances were obtained continuously during CO2 rebreathing (Read's method) and during the 2 min after a 1-min voluntary maximal hyperventilation. The inspiratory drive was estimated by measurements of inspiratory pressure generated at 0.1 s after the onset of inspiration (P0.1) and by the mean inspiratory flow (VT/TI). In each subject both resistances decreased during CO2 rebreathing; these decreases were correlated with the increase in P0.1. During the posthyperventilation period, ventilation fell below base line in seven subjects; this was accompanied by an increase in both nasal and pharyngeal resistances. These resistances increased exponentially as VT/TI decreased. Parallel changes in nasal and pharyngeal resistances were seen during CO2 stimulus and during the period after the hyperventilation. We conclude that 1) the indexes quantifying the inspiratory drive reflect the activation of nasopharyngeal dilator muscles (as assessed by the changes in upper airway resistance) and 2) both nasal and pharyngeal resistances are similarly influenced by changes in the respiratory drive.