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.     

Effect of sleep state and hypercapnia on alae nasi and diaphragm EMGs in preterm infants

A coordinated activation of upper airway and chest wall muscles may be crucial in maintaining airway patency and ventilation. The alae nasi (AN) and diaphragm (DIA) electromyograms (EMG) were recorded with surface electrodes in 17 unsedated healthy preterm infants during both active (AS) and quiet sleep (QS). Airflow was measured via a nasal mask pneumotachograph and integrated to obtain tidal volume. Studies were performed during inhalation of room air and mixtures of 2 and 4% CO2 in air. In room air, phasic AN EMG accompanied 45 +/- 7% of breaths during AS compared with 14 +/- 5% of breaths during QS (P less than 0.001); however, with inhalation of 4% CO2 the incidence of AN EMG increased to comparable levels in both sleep states. During room air breathing onset of AN EMG preceded that of the DIA EMG and inspiratory airflow by 41 +/- 8 ms (P less than 0.01) and 114 +/- 29 ms (P less than 0.05), respectively. Peak AN activity preceded peak DIA activity by 191 +/- 36 ms (P less than 0.01). Alteration in sleep state or increasing chemical drive did not significantly alter these temporal relationships. Nevertheless, with each increase in end-tidal CO2, peak DIA EMG and tidal volume increased while peak AN EMG only showed a consistent increase during 4% CO2 inhalation. We conclude that although there exists a mechanism that temporally coordinates AN and DIA activation, the amount of AN EMG activity with each breath is not clearly correlated with DIA activation, which may contribute to the high incidence of respiratory dysrhythmias in preterm neonates.     

End-tidal CO2 response to low levels of inspired CO2 in awake beagle dogs

The steady-state end-tidal CO2 tension (PCO2) was examined during control and 1% CO2 inhalation periods in awake beagle dogs with an intact airway breathing through a low dead-space respiratory mask. A total of eight experiments were performed in four dogs, comprising 31 control observations and 23 CO2 inhalation observations. The 1% inhaled CO2 produced a significant increase in the steady-state end-tidal PCO2 comparable to the expected 1 Torr predicted from conventional CO2 control of ventilation. We conclude that 1% inhaled CO2 results in a hypercapnia. Any protocol that is to resolve the question of whether mechanisms are acting during low levels of inhaled CO2 such that ventilation increases without any change in arterial PCO2 must have sufficient resolving power to discriminate changes in gas tension in magnitude predicted from conventional (i.e., arterial PCO2) control of ventilation.     

Carotid body denervation in dogs: eupnea and the ventilatory response to hyperoxic hypercapnia.

We assessed the time course of changes in eupneic arterial PCO(2) (Pa(CO(2))) and the ventilatory response to hyperoxic rebreathing after removal of the carotid bodies (CBX) in awake female dogs. Elimination of the ventilatory response to bolus intravenous injections of NaCN was used to confirm CBX status on each day of data collection. Relative to eupneic control (Pa(CO(2)) = 40 +/- 3 Torr), all seven dogs hypoventilated after CBX, reaching a maximum Pa(CO(2)) of 53 +/- 6 Torr by day 3 post-CBX. There was no significant recovery of eupneic Pa(CO(2)) over the ensuing 18 days. Relative to control, the hyperoxic CO(2) ventilatory (change in inspired minute ventilation/change in end-tidal PCO(2)) and tidal volume (change in tidal volume/ change in end-tidal PCO(2)) response slopes were decreased 40 +/- 15 and 35 +/- 20% by day 2 post-CBX. There was no recovery in the ventilatory or tidal volume response slopes to hyperoxic hypercapnia over the ensuing 19 days. We conclude that 1) the carotid bodies contribute approximately 40% of the eupneic drive to breathe and the ventilatory response to hyperoxic hypercapnia and 2) there is no recovery in the eupneic drive to breathe or the ventilatory response to hyperoxic hypercapnia after removal of the carotid chemoreceptors, indicating a lack of central or aortic chemoreceptor plasticity in the adult dog after CBX.     

Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep.

We hypothesized that a decreased susceptibility to the development of hypocapnic central apnea during non-rapid eye movement (NREM) sleep in women compared with men could be an explanation for the gender difference in the sleep apnea/hypopnea syndrome. We studied eight men (age 25-35 yr) and eight women in the midluteal phase of the menstrual cycle (age 21-43 yr); we repeated studies in six women during the midfollicular phase. Hypocapnia was induced via nasal mechanical ventilation for 3 min, with respiratory frequency matched to eupneic frequency. Tidal volume (VT) was increased between 110 and 200% of eupneic control. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea, depending on the magnitude of hypocapnia. Nadir minute ventilation in the recovery period was plotted against the change in end-tidal PCO(2) (PET(CO(2))) per trial; minute ventilation was given a value of 0 during central apnea. The apneic threshold was defined as the x-intercept of the linear regression line. In women, induction of a central apnea required an increase in VT to 155 +/- 29% (mean +/- SD) and a reduction of PET(CO(2)) by -4.72 +/- 0.57 Torr. In men, induction of a central apnea required an increase in VT to 142 +/- 13% and a reduction of PET(CO(2)) by -3.54 +/- 0.31 Torr (P = 0.002). There was no difference in the apneic threshold between the follicular and the luteal phase in women. Premenopausal women are less susceptible to hypocapnic disfacilitation during NREM sleep than men. This effect was not explained by progesterone. Preservation of ventilatory motor output during hypocapnia may explain the gender difference in sleep apnea.     

Abdominal muscle activity during CO2 rebreathing in sleeping neonates

Comparison of the abdominal muscle response to CO2 rebreathing in rapid-eye-movement (REM) and non-REM (NREM) sleep was performed in healthy premature infants near full term. Eight subjects were studied at a postconceptional age of 40 +/- 1.6 (SD) wk (range 38-43 wk) during spontaneous sleep. Sleep stages were defined on the basis of electrophysiological and behavioral criteria, and diaphragmatic and abdominal muscle electromyographic activity was recorded by cutaneous electrodes. The responses to CO2 were measured by a modified Read rebreathing technique. The minute ventilation and diaphragmatic and abdominal muscle electromyographic activities were calculated and plotted against end-tidal CO2 partial pressure. Both the ventilatory and diaphragmatic muscle responses to CO2 decreased from NREM to REM sleep (P less than 0.05). Abdominal muscles were forcefully recruited in response to CO2 rebreathing during NREM sleep. In REM sleep, abdominal muscle response to CO2 was virtually absent or decreased compared with NREM sleep (P less than 0.05). We conclude that 1) the abdominal muscles are recruited during NREM sleep in response to CO2 rebreathing in healthy premature infants near full term and 2) the abdominal muscle recruitment is inhibited during REM sleep compared with NREM sleep, and this REM sleep-related inhibition probably contributes to the decrease in the ventilatory response to CO2 rebreathing in REM sleep.     

Upper airway muscle responsiveness to rising PCO(2) during NREM sleep.

Although pharyngeal muscles respond robustly to increasing PCO(2) during wakefulness, the effect of hypercapnia on upper airway muscle activation during sleep has not been carefully assessed. This may be important, because it has been hypothesized that CO(2)-driven muscle activation may importantly stabilize the upper airway during stages 3 and 4 sleep. To test this hypothesis, we measured ventilation, airway resistance, genioglossus (GG) and tensor palatini (TP) electromyogram (EMG), plus end-tidal PCO(2) (PET(CO(2))) in 18 subjects during wakefulness, stage 2, and slow-wave sleep (SWS). Responses of ventilation and muscle EMG to administered CO(2) (PET(CO(2)) = 6 Torr above the eupneic level) were also assessed during SWS (n = 9) or stage 2 sleep (n = 7). PET(CO(2)) increased spontaneously by 0.8 +/- 0.1 Torr from stage 2 to SWS (from 43.3 +/- 0.6 to 44.1 +/- 0.5 Torr, P < 0.05), with no significant change in GG or TP EMG. Despite a significant increase in minute ventilation with induced hypercapnia (from 8.3 +/- 0.1 to 11.9 +/- 0.3 l/min in stage 2 and 8.6 +/- 0.4 to 12.7 +/- 0.4 l/min in SWS, P < 0.05 for both), there was no significant change in the GG or TP EMG. These data indicate that supraphysiological levels of PET(CO(2)) (50.4 +/- 1.6 Torr in stage 2, and 50.4 +/- 0.9 Torr in SWS) are not a major independent stimulus to pharyngeal dilator muscle activation during either SWS or stage 2 sleep. Thus hypercapnia-induced pharyngeal dilator muscle activation alone is unlikely to explain the paucity of sleep-disordered breathing events during SWS.     

Effect of aging on ventilatory response to exercise and CO2

Studies were performed to determine the effects of aging on the ventilatory responsiveness to two known respiratory stimulants, inhaled CO2 and exercise. Although explanation of the physiological mechanisms underlying development of exercise hyperpnea remains elusive, there is much circumstantial evidence that during exercise, however mediated, ventilation is coupled to CO2 production. Thus matched groups of young and elderly subjects were studied to determine the relationship between increasing ventilation and increasing CO2 production (VCO2) during steady-state exercise and the change in their minute ventilation in response to progressive hypercapnia during CO2 rebreathing. We found that the slope of the ventilatory response to hypercapnia was depressed in elderly subjects when compared with the younger control group (delta VE/delta PCO2 = 1.64 +/- 0.21 vs. 2.44 +/- 0.40 l X min-1 X mmHg-1, means +/- SE, respectively). In contrast, the slope of the relationship between ventilation and CO2 production during exercise in the elderly was greater than that of younger subjects (delta VE/delta VCO2 = 29.7 +/- 1.19 vs. 25.3 +/- 1.54, means +/- SE, respectively), as was minute ventilation at a single work load (50 W) (32.4 +/- 2.3 vs. 25.7 +/- 1.54 l/min, means +/- SE, respectively). This increased ventilation during exercise in the elderly was not produced by arterial O2 desaturation, and increased anaerobiasis did not play a role. Instead, the increased ventilation during exercise seems to compensate for increased inefficiency of gas exchange such that exercise remains essentially isocapnic. In conclusion, in the elderly the ventilatory response to hypercapnia is less than in young subjects, whereas the ventilatory response to exercise is greater.     

Validation of a maskless CO2-response test for sleep and infant studies

The Hazinski method is an indirect, noninvasive, and maskless CO2-response test useful in infants or during sleep. It measures the classic CO2-response slope (i.e., delta VI/delta PCO2) divided by resting ventilation Sr = (VI'--VI')/(VI'.delta PCO2) between low (')- and high (')-inspired CO2 as the fractional increase of alveolar ventilation per Torr rise of PCO2. In steady states when CO2 excretion (VCO2') = VCO2', Hazinski CO2-response slope (Sr) may be computed from the alveolar exchange equation as Sr = (PACO2'--PICO2')/(PACO2'--PICO2') where PICO2 is inspired PCO2. To avoid use of a mask or mouthpiece, the subject breathes from a hood in which CO2 is mixed with inspired air and a transcutaneous CO2 electrode is used to estimate alveolar PCO2 (PACO2). To test the validity of this method, we compared the slopes measured simultaneously by the Hazinski and standard steady-state methods using a pneumotachograph, mask, and end-tidal, arterial, and four transcutaneous PCO2 samples in 15-min steady-state challenges at PICO2 23.5 +/- 4.5 and 37 +/- 4.1 Torr. Sr was computed using PACO2 and arterial PCO2 (PaCO2) as well as with the four skin PCO2 (PSCO2) values. After correction for apparatus dead space, the standard method was normalized to resting VI = 1, and its CO2 slope was designated directly measured normalized CO2 slope (Sx), permitting error to be calculated as Sr/Sx.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of the central chemosensitivity in man under transient or progressive hypercapnia

In healthy man, the central chemosensitivity to CO2 was studied after depression of the arterial chemoreflex drive by inhalation of pure oxygen. The effectiveness of the functional decrease of arterial chemoreceptor function was assessed by the delayed hyperventilation which followed transient inhalation of hypercapnic gas mixtures for 3 or 5 breaths in hyperoxic conditions. In such a case the first significant increase in tidal volume (VT) occurred 13.9 +/- 3.2 (SE) sec later than the early change in this variable measured in normoxic conditions. The stimulus strength was estimated by the change in CO2 partial pressure in end-tidal alveolar gas (delta PETCO2). The central chemosensitivity (SCO2), defined as the ratio between change in ventilation (delta V) and delta PETCO2, was assessed either by transient inhalation of gas mixtures containing 5 to 8% CO2 in pure O2 ("varying transients") or by progressive hypercapnia (rebreathing in pure O2). In both cases, the first significant change in ventilation was due to an increase in VT, but, for a given delta PETCO2, VT changes were higher during rebreathing than after transient hypercapnia; (2) The respiratory frequency (fR) was progressively enhanced during rebreathing (shortening of expiratory duration in all cases and of inspiratory time in some subjects) but the ventilatory rhythm diminished after transient stimulation as soon as delta PETCO2 reached one kPa, and this was due to an increase in inspiratory duration; (3) The associated changes in VT and fR during rebreathing could explain that SCO2 values given by this method were 5.2 times greater than after transient hypercapnia ("varying tests"). The differences are discussed in terms of, (1) isolated changes in arterial PCO2 or associated decrease in pH of the cerebrospinal fluid; (2) changes in brain blood flow, and (3) stimulation of lung stretch receptors by the important increase in VT during rebreathing.     

Increased propensity for apnea via dopamine-induced carotid body inhibition in sleeping dogs.

We determined the effects of specific carotid body chemoreceptor inhibition on the propensity for apnea during sleep. We reduced the responsiveness of the carotid body chemoreceptors using intravenous dopamine infusions during non-rapid eye movement sleep in six dogs. Then we quantified the difference in end-tidal Pco(2) (Pet(CO(2))) between eupnea and the apneic threshold, the "CO(2) reserve," by gradually reducing Pet(CO(2)) transiently with pressure support ventilation at progressively increased tidal volume until apnea occurred. Dopamine infusions decreased steady-state eupneic ventilation by 15 +/- 6%, causing a mean CO(2) retention of 3.9 +/- 1.9 mmHg and a brief period of ventilatory instability. The apneic threshold Pet(CO(2)) rose 5.1 +/- 1.9 Torr; thus the CO(2) reserve was narrowed from -3.9 +/- 0.62 Torr in control to -2.7 +/- 0.78 Torr with dopamine. This decrease in the CO(2) reserve with dopamine resulted solely from the 20.5 +/- 11.3% increase in plant gain; the slope of the ventilatory response to CO(2) below eupnea was unchanged from normal. We conclude that specific carotid chemoreceptor inhibition with dopamine increases the propensity for apnea during sleep by narrowing the CO(2) reserve below eupnea. This narrowing is due solely to an increase in plant gain as the slope of the ventilatory response to CO(2) below eupnea was unchanged from normal control. These findings have implications for the role of chemoreceptor inhibition/stimulation in the genesis of apnea and breathing periodicity during sleep.     

Respiratory effects in humans of a 5-day elevation of end-tidal PCO2 by 8 Torr.

The aims of this study were to determine 1) whether ventilatory adaptation occurred over a 5-day exposure to a constant elevation in end-tidal PCO2 and 2) whether such an exposure altered the sensitivity of the chemoreflexes to acute hypoxia and hypercapnia. Ten healthy human subjects were studied over a period of 13 days. Their ventilation, chemoreflex sensitivities, and acid-base status were measured daily before, during, and after 5 days of elevated end-tidal PCO2 at 8 Torr above normal. There was no major adaptation of ventilation during the 5 days of hypercapnic exposure. There was an increase in ventilatory chemosensitivity to acute hypoxia (from 1.35 +/- 0.08 to 1.70 +/- 0.07 l/min/%; P < 0.01) but no change in ventilatory chemosensitivity to acute hypercapnia. There was a degree of compensatory metabolic alkalosis. The results do not support the hypothesis that the ventilatory adaptation to chronic hypercapnia would be much greater with constant elevation of alveolar PCO2 than with constant elevation of inspired PCO2, as has been used in previous studies and in which the feedback loop between ventilation and alveolar PCO2 is left intact.     

Effect of chest wall vibration on breathlessness in normal subjects

This study evaluated the effect of chest wall vibration (115 Hz) on breathlessness. Breathlessness was induced in normal subjects by a combination of hypercapnia and an inspiratory resistive load; both minute ventilation and end-tidal CO2 were kept constant. Cross-modality matching was used to rate breathlessness. Ratings during intercostal vibration were expressed as a percentage of ratings during the control condition (either deltoid vibration or no vibration). To evaluate their potential contribution to any changes in breathlessness, we assessed several aspects of ventilation, including chest wall configuration, functional residual capacity (FRC), and the ventilatory response to steady-state hypercapnia. Intercostal vibration reduced breathlessness ratings by 6.5 +/- 5.7% compared with deltoid vibration (P less than 0.05) and by 7.0 +/- 8.3% compared with no vibration (P less than 0.05). The reduction in breathlessness was accompanied by either no change or negligible change in minute ventilation, tidal volume, frequency, duty cycle, compartmental ventilation, FRC, and the steady-state hypercapnic response. We conclude that chest wall vibration reduces breathlessness and speculate that it may do so through stimulation of receptors in the chest wall.     

Effect of inspiratory resistive loading on control of ventilation during progressive exercise

Eight healthy volunteers performed gradational tests to exhaustion on a mechanically braked cycle ergometer, with and without the addition of an inspiratory resistive load. Mean slopes for linear ventilatory responses during loaded and unloaded exercise [change in minute ventilation per change in CO2 output (delta VE/delta VCO2)] measured below the anaerobic threshold were 24.1 +/- 1.3 (SE) = l/l of CO2 and 26.2 +/- 1.0 l/l of CO2, respectively (P greater than 0.10). During loaded exercise, decrements in VE, tidal volume, respiratory frequency, arterial O2 saturation, and increases in end-tidal CO2 tension were observed only when work loads exceeded 65% of the unloaded maximum. There was a significant correlation between the resting ventilatory response to hypercapnia delta VE/delta PCO2 and the ventilatory response to VCO2 during exercise (delta VE/delta VCO2; r = 0.88; P less than 0.05). The maximal inspiratory pressure generated during loading correlated with CO2 sensitivity at rest (r = 0.91; P less than 0.05) and with exercise ventilation (delta VE/delta VCO2; r = 0.83; P less than 0.05). Although resistive loading did not alter O2 uptake (VO2) or heart rate (HR) as a function of work load, maximal VO2, HR, and exercise tolerance were decreased to 90% of control values. We conclude that a modest inspiratory resistive load reduces maximum exercise capacity and that CO2 responsiveness may play a role in the control of breathing during exercise when airway resistance is artificially increased.     

Effect of plasma carbonic anhydrase on ventilation in exercising dogs

Recent studies suggest pH sampled by arterial chemoreceptors may not equal that sampled by external pH electrodes, because the uncatalyzed hydration of CO2 in plasma is a slow reaction (t 1/2 approximately 9 S). The importance of this reaction rate to ventilatory control (particularly during exercise) is not known. We studied the effect of catalyzing the CO2-pH reaction in three awake exercising dogs with chronic tracheostomies and carotid loops; the dogs were trained to run on a treadmill. Respiration frequency, tidal volume, total ventilation, and end-tidal partial pressure of CO2 (PCO2) were continuously monitored. Periodically, carotid artery blood was drawn and analyzed for partial pressure of O2 (PO2), PCO2, pH, and plasma carbonic anhydrase (CA) activity. Measurements were made during steady-state exercise (3 mph and 10% grade), during a control period, after injection of a 5 ml bolus of saline, and after injection of 5 mg/kg of bovine CA dissolved in 5 ml of saline. This dose of CA increased the reaction rate by more than 80-fold. Neither the control nor the CA injections significantly altered the ventilatory parameters. Saline and CA date differed by less than 5% in ventilation, 1 Torr in arterial PCO2, 0.01 in pH units, and 1.5 Torr in end-tidal PCO2. Thus the of CO2 hydration in plasma is not a significant factor in ventilatory control.     

Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness

Persons with acute altitude sickness hypoventilate at high altitude compared with persons without symptoms. We hypothesized that their hypoventilation was due to low initial hypoxic ventilatory responsiveness, combined with subsequent blunting of ventilation by hypocapnia and/or prolonged hypoxia. To test this hypothesis, we compared eight subjects with histories of acute altitude sickness with four subjects who had been asymptomatic during prior altitude exposure. At a simulated altitude of 4,800 m, the eight susceptible subjects developed symptoms of altitude sickness and had lower minute ventilations and higher end-tidal PCO2's than the four asymptomatic subjects. In measurements made prior to altitude exposure, ventilatory responsiveness to acute hypoxia was reduced in symptomatic compared to asymptomatic subjects, both when measured under isocapnic and poikolocapnic (no added CO2) conditions. Diminution of the poikilocapnic relative to the isocapnic hypoxic response was similar in the two groups. Ventilation fell, and end-tidal PCO2 rose in both groups during 30 min of steady-state hypoxia relative to values observed acutely. After 4.5 h at 4,800 m, ventilation was lower than values observed acutely at the same arterial O2 saturation. The reduction in ventilation in relation to the hypoxemia present was greater in symptomatic than in asymptomatic persons. Thus the hypoventilation in symptomatic compared to asymptomatic subjects was attributable both to a lower acute hypoxic response and a subsequent greater blunting of ventilation at high altitude.     

Effect of airway impedance on CO2 retention and respiratory muscle activity during NREM sleep

We hypothesized that a sleep-induced increase in mechanical impedance contributes to CO2 retention and respiratory muscle recruitment during non-rapid-eye-movement (NREM) sleep. The effect NREM sleep on respiratory muscle activity and CO2 retention was measured in healthy subjects who increased maximum total pulmonary resistance (RLmax, 1-81 cmH2O.l-1.s) from awake to NREM sleep. We determined the effects of this sleep-induced increase in airway impedance by steady-state inhalation of a reduced-density gas mixture (79% He-21% O2, He-O2). Both arterialized blood PCO2 (PaCO2) and end-tidal PCO2 (PETCO2) were measured. Inspiratory (EMGinsp) and expiratory (EMGexp) respiratory muscle electromyogram activity was measured. NREM sleep caused 1) RLmax to increase (7 +/- 3 vs. 39 +/- 28 cmH2O.l-1.s), 2) PaCO2 and/or PETCO2 to increase in all subjects (40 +/- 2 vs. 44 +/- 3 Torr), and 3) EMGinsp to increase in 8 of 9 subjects and EMGexp to increase in 9 of 17 subjects. Compared with steady-state air breathing during NREM sleep, steady-state He-O2 breathing 1) reduced RLmax by 38%, 2) decreased PaCO2 and PETCO2 by 2 Torr, and 3) decreased both EMGinsp (-20%) and EMGexp (-54%). We concluded that the sleep-induced increase in upper airway resistance accompanied by the absence of immediate load compensation is an important determinant of CO2 retention, which, in turn, may cause augmentation of inspiratory and expiratory muscle activity above waking levels during NREM sleep.     

Ventilatory response of the sleeping newborn to CO2 during normoxic rebreathing

The ventilatory response of the newborn to CO2 was studied using a rebreathing method that minimized changes in arterial PO2 during the test. The aim was to study the variability of the ventilatory response to CO2 and take this into account to assess the relative magnitude of the response to CO2 during rapid-eye-movement (REM) sleep and quiet sleep (QS). Five full-term babies aged 4-6 days were given 5% CO2 in air to rebreathe for 1.5-3 min. O2 was added to the rebreathing circuit to maintain arterial O2 saturation and transcutaneous PO2 (Ptco2) at prerebreathing levels. Tests were repeated four to five times in REM sleep and QS. Mean Ptco2 levels varied between individuals but were similar during REM sleep and QS tests for each subject. The mean coefficient of variability of the ventilatory response was 35% (range 15-77%) during QS and 120% (range 32-220%) during REM sleep. PtcO2 fluctuations during tests [6.0 +/- 3.0 (SD) Torr, range 1-13 Torr] were not correlated with ventilatory response. Overall the ventilatory response was significantly lower in REM sleep than in QS (12.2 +/- 3.0 vs. 38.7 +/- 3.0 ml.min-1.Torr-1.kg-1, P less than 0.001; 2-way analysis of variance) due to a small (nonsignificant) fall in the tidal volume response and a significant fall in breathing rate. In 12 REM sleep tests there was no significant ventilatory response; mean inspiratory flow increased significantly during 8 of these 12 tests. We conclude that there is a significant decrease in the ventilatory response of the newborn to CO2 rebreathing during REM sleep compared with QS.     

Posthypoxic ventilatory decline during NREM sleep: influence of sleep apnea.

We wished to determine the severity of posthypoxic ventilatory decline in patients with sleep apnea relative to normal subjects during sleep. We studied 11 men with sleep apnea/hypopnea syndrome and 11 normal men during non-rapid eye movement sleep. We measured EEG, electrooculogram, arterial O(2) saturation, and end-tidal P(CO2). To maintain upper airway patency in patients with sleep apnea, nasal continuous positive pressure was applied at a level sufficient to eliminate apneas and hypopneas. We compared the prehypoxic control (C) with posthypoxic recovery breaths. Nadir minute ventilation in normal subjects was 6.3 +/- 0.5 l/min (83.8 +/- 5.7% of room air control) vs. 6.7 +/- 0.9 l/min, 69.1 +/- 8.5% of room air control in obstructive sleep apnea (OSA) patients; nadir minute ventilation (% of control) was lower in patients with OSA relative to normal subjects (P < 0.05). Nadir tidal volume was 0.55 +/- 0.05 liter (80.0 +/- 6.6% of room air control) in OSA patients vs. 0.42 +/- 0.03 liter, 86.5 +/- 5.2% of room air control in normal subjects. In addition, prolongation of expiratory time (Te) occurred in the recovery period. There was a significant difference in Te prolongation between normal subjects (2.61 +/- 0.3 s, 120 +/- 11.2% of C) and OSA patients (5.6 +/- 1.5 s, 292 +/- 127.6% of C) (P < 0.006). In conclusion, 1) posthypoxic ventilatory decline occurred after termination of hypocapnic hypoxia in normal subjects and patients with sleep apnea and manifested as decreased tidal volume and prolongation of Te; and 2) posthypoxic ventilatory prolongation of Te was more pronounced in patients with sleep apnea relative to normal subjects.     

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.