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.     

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.     

Long-lasting ventilatory response of humans to a single breath of hypercapnia in hyperoxia.

It has often been assumed that under normoxia, closed-loop ventilatory responses to transient CO2 stimulation (i.e., lasting for 1-3 breaths) are less likely to be mediated by the slow-responding central (medullary) chemoreflex. This assumption, however, has not been quantitatively examined in humans. We hypothesized that in the closed-loop respiratory chemical feedback system [in which the centrally mediated ventilatory response to transient changes in the arterial PCO2 levels (PaCO2) will in turn affect the pulmonary CO2 and hence PaCO2], the contribution of the central chemoreflex pathways to brief disturbances in blood gases may be more important than considered previously. Using the technique of pseudorandom binary CO2 stimulation, we quantified the ventilatory response of normal humans to brief disturbances in arterial CO2 during hyperoxia. Tidal volume (VI), inspiratory ventilation (VI), inspiratory time (TI), expiratory time (TE), and end-tidal CO2 fraction (FETCO2) were measured in subjects who inhaled a mixture that was pseudorandomly switched between 95% O2-5% CO2 and 100% O2 (63 breath sequences). From these data, we calculated the responses of VI, VI, TI, TE, and FETCO2 to a single-breath inhalation of 1% CO2 in O2. Our results showed that in response to a brief increase of 0.75 Torr in alveolar CO2, VI showed a transient increase (average peak response of 0.12 1/min) that persisted for greater than or equal to 80 s in every subject. The response of VI was similar to that of VI, whereas TI and TE showed no consistent changes. Using these results we calculated that central chemoreflex pathways may contribute significantly to typical transient CO2 stimulation tests in hyperoxic and normoxic humans.     

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.     

Breathing patterns during submaximal and maximal exercise in elite oarsmen

Continuous breath-by-breath measurements of ventilatory parameters were performed during submaximal and maximal treadmill exercise in 21 highly conditioned oarsmen. Average maximum values of O2 uptake, minute ventilation (VI), tidal volume (VT), and respiratory frequency (f) were 6.60 l/min (73.5 ml X kg-1 X min-1), 200 l/min, 3.29 l, and 62 breaths/min, respectively. During the transition from moderate to heavy submaximal exercise, VT and f increased progressively. At near-maximal to maximal work loads, VT plateaued and then decreased slightly, while f continued to increase. Increase in f at the start of exercise was achieved predominantly by an abrupt decrease in expiratory duration (TE) with an equally abrupt, but much smaller, decrease in inspiratory duration (TI). During the transition from submaximal to maximal exercise, both TE and TI decreased progressively. Although f appeared to be entrained by stepping rate in a few subjects, the dominant trend during submaximal to maximal exercise was characterized by a relatively small increase in stepping rate with a much larger increment in f. Our data are consistent with the conclusion that exercise breathing patterns are determined by many interacting factors that vary at different work loads, in different individuals, and are probably also influenced by physical conditioning and previous experience.     

Mechanical impedance as determinant of inspiratory neural drive during exercise in humans

Five healthy males exercised progressively with small 2-min increments in work load. We measured inspiratory drive (occlusion pressure, P0.1), pulmonary resistance (RL), dynamic pulmonary compliance (Cdyn), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi). Minute ventilation (VE), mean inspiratory flow rate (VT/TI), and P0.1 all increased exponentially with increased work load, but P0.1 increased at a faster rate than did VT/TI or VE. Thus effective impedance (P0.1/VT/TI) rose throughout exercise. The increasing P0.1 was mostly due to augmented Pdi and coincided with increased EMGdi during this initial portion of inspiration. We found no consistent change in RL or Cdyn throughout exercise. With He breathing (80% He-20% O2), RL was reduced at all work loads; P0.1 fell in comparison with air-breathing values and VE, VT, and VT/TI rose in moderate and heavy work; and P0.1/VT/TI was unchanged with increasing exercise loads. Step reductions in gas density at a constant work load of any intensity showed an immediate reduction in the rate of rise of EMGdi and Pdi followed by increased VT/TI, breathing frequency, and hypocapnia. These changes were maintained during prolonged periods of unloading and were immediately reversible on return to air breathing. These data are consistent with the existence of a reflex effect on the magnitude of inspiratory neural drive during exercise that is sensitive to the load presented by the normal mechanical time constant of the respiratory system. This "load" is a significant determinant of the hyperpneic response and thus of the maintenance of normocapnia during exercise.     

Respiratory load compensation in chronic airway obstruction

To assess respiratory neuromuscular function and load compensating ability in patients with chronic airway obstruction (CAO), we studied eight stable patients with irreversible airway obstruction during hyperoxic CO2 rebreathing with and without a 17 cmH2O X l-1 X s flow-resistive inspiratory load (IRL). Minute ventilation (VE), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi) were monitored. Pdi and EMGdi were obtained via a single gastroesophageal catheter with EMGdi being quantitated as the average rate of rise of inspiratory (moving average) activity. Based on the effects of IRL on the Pdi response to CO2 [delta Pdi/delta arterial CO2 tension (PaCO2)] and the change in Pdi for a given change in EMGdi (delta Pdi/delta EMGdi) during rebreathing, two groups could be clearly identified. Four patients (group A) were able to increase delta Pdi/delta PaCO2 and delta Pdi/delta EMGdi, whereas in the other four (group B) the IRL responses decreased. All group B patients were hyperinflated having significantly greater functional residual capacity (FRC) and residual volume than group A. In addition the IRL induced percent change in delta Pdi/delta PaCO2, and delta VE/delta PaCO2 was negatively correlated with lung volume so that in the hyperinflated group B the higher the FRC the greater was the decrease in Pdi response due to IRL. In both groups the greater the FRC the greater was the decrease in the ventilatory response to loading. Patients with CAO, even with severe airways obstruction, can effect load compensation by increasing diaphragmatic force output, but the presence of increased lung volume with the associated shortened diaphragm prevents such load compensation.     

Breathing pattern during exercise in young black and Caucasian subjects

Lung volumes in sex-, age-, height-, and weight-matched Black subjects are 10-15% lower than those in Caucasians. To determine whether this decreased lung volume affected the ventilatory adaptation to exercise, minute ventilation (VE), its components, frequency (f) and tidal volume (VT), and breathing pattern were observed during incremental cycle-ergometer exercise. Eighteen Caucasian (age 8-30 yr) and 14 Black (age 8-25 yr) subjects were studied. Vital capacity (VC) was lower (P less than 0.001) in the Black subjects [90.6 +/- 8.6 (SD) vs. 112.9 +/- 9.9% predicted], whereas functional residual capacity/total lung capacity was higher (P less than 0.05). VE, mixed expired O2 and CO2, VT, f, and inspiratory (TI), expiratory (TE), and total respiratory cycle (TT) duration were measured during the last 30 s of each 2-min load. Statistical comparisons with increasing power output were made at rest and from 0.6 to 2.4 W/kg in 0.3-W/kg increments. VE was higher in Blacks at all work loads and reached significance (P less than 0.05) at 0.6 and 1.5 W/kg. VE/VO2 was also higher throughout exercise, reaching significance (P less than 0.01) at 1.2, 1.5, and 1.8 W/kg. The Black subjects attained any given level of VE with a higher f (P less than 0.001) and lower VT. TI and TE were shortened proportionately so that TI/TT was not different. Differences in lung volume and the ventilatory response to exercise in these Black and Caucasian subjects suggest differences in the respiratory pressure-volume relationships or that the Black subjects may breathe higher on their pressure-volume curve.     

Effect of resistive loads on pattern of respiratory muscle recruitment during exercise.

In healthy subjects, we compared the effects of an expiratory (ERL) and an inspiratory (IRL) resistive load (6 cmH2O.l-1.s) with no added resistive load on the pattern of respiratory muscle recruitment during exercise. Fifteen male subjects performed three exercise tests at 40% of maximum O2 uptake: 1) with no-added-resistive load (control), 2) with ERL, and 3) with IRL. In all subjects, we measured breathing pattern and mouth occlusion pressure (P0.1) from the 3rd min of exercise, in 10 subjects O2 uptake (VO2), CO2 output (VCO2), and respiratory exchange ratio (R), and in 5 subjects we measured gastric (Pga), pleural (Ppl), and transdiaphragmatic (Pdi) pressures. Both ERL and IRL induced a high increase of P0.1 and a decrease of minute ventilation. ERL induced a prolongation of expiratory time with a reduction of inspiratory time (TI), mean expiratory flow, and ratio of inspiratory to total time of the respiratory cycle (TI/TT). IRL induced a prolongation of TI with a decrease of mean inspiratory flow and an increase of tidal volume and TI/TT. With ERL, in two subjects, Pga increased and Ppl decreased more during inspiration than during control suggesting that the diaphragm was the most active muscle. In one subject, the increases of Ppl and Pga were weak; thus Pdi increased very little. In the two other subjects, Ppl decreased more during inspiration but Pga also decreased, leading to a decrease of Pdi. This suggests a recruitment of abdominal muscles during expiration and of accessory and intercostal muscles during inspiration. With IRL, in all subjects, Ppl again decreased more, Pga began to decrease until 40% of TI and then increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Phonospirometry for noninvasive measurement of ventilation: methodology and preliminary results.

We measured tracheal flow from tracheal sounds to estimate tidal volume, minute ventilation (VI), respiratory frequency, mean inspiratory flow (VT/TI), and duty cycle (TI/Ttot). In 11 normal subjects, 3 patients with unstable airway obstruction, and 3 stable asthmatic patients, we measured tracheal sounds and flow twice: first to derive flow-sound relationships and second to obtain flow-volume relationships from the sound signal. The flow-volume relationship was compared with pneumotach-derived volume. When subjects were seated, facing forward and with neck rotation, flexion, and standing, flow-volume relationship was within 15% of pneumotach-derived volume. Error increased with neck extension and while supine. We then measured ventilation without mouthpiece or nose clip from tracheal sounds during quiet breathing for up to 30 min. Normal results +/- SD revealed tidal volume = 0.37 +/- 0.065 liter, respiratory frequency = 19.3 +/- 3.5 breaths/min, VI = 6.9 +/- 1.2 l/min, VT/TI = 0.31 +/- 0.06 l/s, and TI/Ttot = 0.37 +/- 0.04. Unstable airway obstruction had large VI due to increased VT/TI. With the exception of TI/Ttot, variations in ventilatory parameters were closer to log normal than normal distributions and tended to be greater in patients. We conclude that phonospirometry measures ventilation reasonably accurately without mouthpiece, nose clip, or rigid postural constraints.     

Interaction between vagal and chemoreceptors afferents in ventilatory response to transient hypercapnia (anaesthetized rabbit).

In rabbits anaesthetized with ethyl-carbamate, stimulation of chemoreceptors afferents was allowed by transient hypercapnia, before and after vagal blockade by DC current. In these relatively fast breathing animals, the transient hypercapnia produced light changes of inspiratory tidal volume (VI), inspiratory (TI) and expiratory durations (TE). Despite the identity of transient hypercapnia, it ensued that: (1) the higher the spontaneous VI and the lower the respiratory frequency (fR), the greater their respective changes (deltaVI and deltafR) during the ventilatory response; (2) after vagal blockade, greater changes in VI, TI, TE and mean inspiratory flow rate (VI/TI) occurred than in control state, while the relation between deltafR and fR was more significant than in control state. Respective roles played by vagal and chemoreceptors afferents in the ventilatory response to transient hypercapnia are discussed.     

Exercise breathing pattern during chronic altitude exposure

Breathing pattern in response to maximal exercise was examined in four subjects during a 7-day acclimatisation to a simulated altitude of 4247 m (barometric pressure, PB = 59.5 kPa). Graded exercise tests to exhaustion were performed during normoxia (day 0), and on days 2 and 7 of hypoxia, respectively. Ventilation was significantly augmented in the hypoxic environment, as were both the mean inspiratory flow (VT/TI) and inspiratory duty cycle (TI/TTOT) components of it. VI/TI was increased due to a significant increase in tidal volume (VT) and a corresponding decrease in inspiratory time duration (TI). Throughout a range of exercise ventilation, TI/TTOT was increased due to an apparently greater decrease in expiratory time duration (TE) with respect to TI. In all cases, the relation between VT and TI displayed a typical range 2 behaviour, with evidence of a range 3 occurring at very high ventilatory rates. There was essentially no difference observed in the VT-TI relation during exercise between the normoxic and hypoxic conditions. No significant changes were observed in the breathing pattern in response to exercise within the exposure period (from day 2 to day 7), although there was a discernible tendency to a higher stage 3 plateau by day 7 of altitude exposure.     

Ventilatory response to sustained hypoxia in normal adults

We examined the ventilatory response to moderate (arterial O2 saturation 80%), sustained, isocapnic hypoxia in 20 young adults. During 25 min of hypoxia, inspiratory minute ventilation (VI) showed an initial brisk increase but then declined to a level intermediate between the initial increase and resting room air VI. The intermediate level of VI was a plateau that did not change significantly when hypoxia was extended up to 1 h. The relation between the amount of initial increase and subsequent decrease in ventilation during constant hypoxia was not random; the magnitude of the eventual decline correlated confidently with the degree of initial hyperventilation. Evaluation of breathing pattern revealed that during constant hypoxia there was little alteration in respiratory timing and that the changes in VI were related to significant alterations in tidal volume and mean inspiratory flow (VT/TI). None of the changes was reproduced during a sham control protocol, in which room air was substituted for the period of low fractional concentration of inspired O2. We conclude that ventilatory response to hypoxia in adults is not sustained; it exhibits some biphasic features similar to the neonatal hypoxic response.     

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.     

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.     

Airway obstruction during periodic breathing in premature infants

To characterize changes in pulmonary resistance, timing, and respiratory drive during periodic breathing, we studied 10 healthy preterm infants (body wt 1,340 +/- 240 g, postconceptional age 35 +/- 2 wk). Periodic breathing in these infants was defined by characteristic cycles of ventilation with intervening respiratory pauses greater than or equal to 2 s. Nasal airflow was recorded with a pneumotachometer, and esophageal or pharyngeal pressure was recorded with a fluid-filled catheter. Pulmonary resistance at half-maximal tidal volume, inspiratory time (TI), expiratory time (TE), and mean inspiratory flow (VT/TI) were derived from computer analysis of five cycles of periodic breathing per infant. In 80% of infants periodic breathing was accompanied by completely obstructed breaths at the onset of ventilatory cycles; the site of airway obstruction occurred within the pharynx. The first one-third of the ventilatory phase of each cycle was accompanied by the highest airway resistance of the entire cycle (168 +/- 98 cmH2O.l-1.s). In all infants TI was greatest at the onset of the ventilatory cycle, VT/TI was maximal at the midpoint of the cycle, and TE was longest in the latter two-thirds of each cycle. A characteristic increase and subsequent decrease of 4.5 +/- 1.9 ml in end-expiratory volume also occurred within each cycle. These results demonstrate that partial or complete airway obstruction occurs during periodic breathing. Both apnea and periodic breathing share the element of upper airway instability common to premature infants.     

Effect of expiratory resistive loading on the noninvasive tension-time index in COPD.

Expiratory resistive loading (ERL) is used by chronic obstructive pulmonary disease (COPD) patients to improve respiratory function. We, therefore, used a noninvasive tension-time index of the inspiratory muscles (TT(mus) = I/PI(max) x TI/TT, where I is mean inspiratory pressure estimated from the mouth occlusion pressure, PI(max) is maximal inspiratory pressure, TI is inspiratory time, and TT is total respiratory cycle time) to better define the effect of ERL on COPD patients. To accomplish this, we measured airway pressures, mouth occlusion pressure, respiratory cycle flow rates, and functional residual capacity (FRC) in 14 COPD patients and 10 normal subjects with and without the application of ERL. TT(mus) was then calculated and found to drop in both COPD and normal subjects (P<0.05). The decline in TT(mus) in both groups resulted solely from a prolongation of expiratory time with ERL (P<0.001 for COPD, P<0.05 for normal subjects). In contrast to the COPD patients, normal subjects had an elevation in I and FRC, thus minimizing the decline in TT(mus). In conclusion, ERL reduces the potential for inspiratory muscle fatigue in COPD by reducing TI/TT without affecting FRC and I.     

Arterial CO2 partial pressure affects diaphragmatic function

The purpose of this study was to examine in an in vivo preparation acute variations of PCO2 on diaphragmatic contractility. Plaster casts were snugly fit around the abdomen of six open-chested dogs, moving the abdominal contents rostrally. Diaphragmatic contractions against this very fixed load in response to phrenic nerve stimulation (supramaximal voltage at 1, 20, 50, and 80 Hz) or during spontaneous inspiratory efforts were virtually isometric (quasi-isometric). Transdiaphragmatic pressure (Pdi) measured by an abdominal balloon was used as an index of diaphragmatic contractility. Arterial PCO2 (PaCO2) was reduced by hyperventilation and raised by increasing PICO2. Pdi values in response to stimulation at 1, 20, 50, and 80 Hz in ranges I (PaCO2 = 0-19 Torr) and II (PaCO2 = 20-34 Torr) did not differ statistically from the control Pdi values (range III; PaCO2 = 35-45 Torr). In range IV (PaCO2 = 46-70 Torr) Pdi values for stimulations of 20, 50, and 80 Hz were significantly lower than control. In range V (PaCO2 = 71-90 Torr), VI (PaCO2 = 91-101 Torr), and VII (PaCO2 greater than or equal to 102 Torr) Pdi values were significantly less than those in range IV at all frequencies of stimulation. In the four dogs measured during spontaneous inspiratory efforts the integrated diaphragmatic electromyogram (Edi) was correlated with the Pdi. As PaCO2 rose (range III to VII), the Pdi values observed at 25, 50, 75, 100% of the maximum Edi (of range III) were significantly lower than the Pdi value of range III.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transient changes in expiratory time during hypercapnia in premature infants

The transient ventilatory responses to hypercapnia were studied in nine healthy preterm infants. We administered 4% CO2 in air for at least 7 min during quiet sleep and measured frequency (f), inspiratory time (TI), expiratory time (TE), tidal volume (VT), and minute ventilation (VI). Frequency increased over the first 2 min of CO2 inhalation (P less than 0.05) and then decreased to control values (P less than 0.05). This response was secondary to changes in TE, which decreased over the first 2 min (P less than 0.05) and then returned to control values, whereas TI did not change. The late increase in TE was associated with an increased percent of breaths exhibiting retardation of expiratory flow (braking) (P less than 0.05). These breaths had longer TE than the breaths without braking (P less than 0.05). Exponential curves made to fit the increases in VI and VT revealed that only 67% of the infants reached 90% of steady state for both VI and VT over the 7-min study period. The time to 90% of steady state was always shorter for VI than VT (P less than 0.05) due to the transient changes in f. The results indicate that the transient changes of f in response to hypercapnia are secondary to changes in TE, which appear unique to human infants. We speculate that the expiratory braking that develops during the course of CO2 inhalation increases lung volume, resulting in prolongation of TE via mechanoreceptor-mediated reflexes.