Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation

1983 ◽  
Vol 55 (3) ◽  
pp. 813-822 ◽  
Author(s):  
J. B. Skatrud ◽  
J. A. Dempsey
Keyword(s):  
Periodic Breathing ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Positive Pressure ◽  
Sleep State ◽  
Co2 Partial Pressure ◽  
Apnea Duration ◽  
O2 Concentration ◽  
End Tidal ◽  
End Tidal Co2

The effect of sleep state on ventilatory rhythmicity following graded hypocapnia was determined in two normal subjects and one patient with a chronic tracheostomy. Passive positive-pressure hyperventilation (PHV) was performed for 3 min awake and during nonrapid-eye-movement (NREM) sleep with hyperoxia [fractional inspired O2 concentration (FIO2) = 0.50], normoxia and hypoxia (FIO2 = 0.12). During wakefulness, no immediate posthyperventilation apnea was noted following abrupt cessation of PHV in 27 of 28 trials [mean hyperventilation end-tidal CO2 partial pressure (PETCO2) 29 +/- 2 Torr, range 22-35]. During spontaneous breathing in hyperoxia, PETCO2 rose from 40.4 +/- 0.7 Torr awake to 43.2 +/- 1.4 Torr during NREM sleep. PHV during NREM sleep caused apnea when PETCO2 was reduced to 3-6 Torr below NREM sleep levels and 1-2 Torr below the waking level. In hypoxia, PETCO2 increased from 37.1 +/- 0.1 awake to 39.8 +/- 0.1 Torr during NREM sleep. PHV caused apnea when PETCO2 was reduced to levels 1-2 Torr below NREM sleep levels and 1-2 Torr above awake levels. Apnea duration (5-45 s) was significantly correlated to the magnitude of hypocapnia (range 27-41 Torr). PHV caused no apnea when isocapnia was maintained via increased inspired CO2. Prolonged hypoxia caused periodic breathing, and the abrupt transition from short-term hypoxic-induced hyperventilation to acute hyperoxia caused apnea during NREM sleep when PETCO2 was lowered to or below the subject's apneic threshold as predetermined (passively) by PHV. We concluded that effective ventilatory rhythmogenesis in the absence of stimuli associated with wakefulness is critically dependent on chemoreceptor stimulation secondary to PCO2-[H+].

Determinants of poststimulus potentiation in humans during NREM sleep

1992 ◽  
Vol 73 (5) ◽  
pp. 1958-1971 ◽  
Author(s):  
M. S. Badr ◽  
J. B. Skatrud ◽  
J. A. Dempsey
Keyword(s):  
Eye Movement ◽  
Control Period ◽  
Periodic Breathing ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Central Apnea ◽  
Inhibitory Effects ◽  
Arterial Pco2 ◽  
End Tidal ◽  
Sustained Hypoxia

To test whether active hyperventilation activates the “afterdischarge” mechanism during non-rapid-eye-movement (NREM) sleep, we investigated the effect of abrupt termination of active hypoxia-induced hyperventilation in normal subjects during NREM sleep. Hypoxia was induced for 15 s, 30 s, 1 min, and 5 min. The last two durations were studied under both isocapnic and hypocapnic conditions. Hypoxia was abruptly terminated with 100% inspiratory O2 fraction. Several room air-to-hyperoxia transitions were performed to establish a control period for hyperoxia after hypoxia transitions. Transient hyperoxia alone was associated with decreased expired ventilation (VE) to 90 +/- 7% of room air. Hyperoxic termination of 1 min of isocapnic hypoxia [end-tidal PO2 (PETO2) 63 +/- 3 Torr] was associated with VE persistently above the hyperoxic control for four to six breaths. In contrast, termination of 30 s or 1 min of hypocapnic hypoxia [PETO2 49 +/- 3 and 48 +/- 2 Torr, respectively; end-tidal PCO2 (PETCO2) decreased by 2.5 or 3.8 Torr, respectively] resulted in hypoventilation for 45 s and prolongation of expiratory duration (TE) for 18 s. Termination of 5 min of isocapnic hypoxia (PETO2 63 +/- 3 Torr) was associated with central apnea (longest TE 200% of room air); VE remained below the hyperoxic control for 49 s. Termination of 5 min of hypocapnic hypoxia (PETO2 64 +/- 4 Torr, PETCO2 decreased by 2.6 Torr) was also associated with central apnea (longest TE 500% of room air). VE remained below the hyperoxic control for 88 s. We conclude that 1) poststimulus hyperpnea occurs in NREM sleep as long as hypoxia is brief and arterial PCO2 is maintained, suggesting the activation of the afterdischarge mechanism; 2) transient hypocapnia overrides the potentiating effects of afterdischarge, resulting in hypoventilation; and 3) sustained hypoxia abolishes the potentiating effects of after-discharge, resulting in central apnea. These data suggest that the inhibitory effects of sustained hypoxia and hypocapnia may interact to cause periodic breathing.

Effects of changes in CO2 partial pressure on the sensation of respiratory drive

1985 ◽  
Vol 59 (6) ◽  
pp. 1747-1751 ◽  
Author(s):  
R. J. Castele ◽  
A. F. Connors ◽  
M. D. Altose
Keyword(s):  
Partial Pressure ◽  
Muscle Force ◽  
Co2 Concentration ◽  
Normal Subjects ◽  
Positive Pressure ◽  
Base Line ◽  
Respiratory Drive ◽  
Respiratory Sensation ◽  
Co2 Partial Pressure ◽  
End Tidal

The purpose of this study was to determine whether a change in respiratory sensation accompanies an increase in CO2 partial pressure (PCO2) in the absence of any changes in the level and pattern of thoracic displacement and respiratory muscle force. Eleven normal subjects were artificially hyperventilated with a positive-pressure mechanical respirator. In separate trials the tidal volume (VT) was set at 10 and 18 ml/kg and the frequency of ventilation (f) was adjusted to maintain the base-line end-tidal PCO2 at approximately 30 Torr. Thereafter, at a constant controlled VT and f, the PCO2 was progressively increased by raising the inspired CO2 concentration. There were no changes in respiratory motor activity as determined from the peak inspiratory airway pressure (Paw) until the PCO2 reached 40.8 +/- 1.0 and 40.1 +/- 1.0 (SE) Torr in the large and small VT trials, respectively. Initially there was no conscious awareness of the change in respiratory activity. Subjects first signaled that ventilatory needs were not being satisfied only after a further increase in PCO2 to 44.7 +/- 1.3 and 42.3 +/- 1.0 (SE) Torr in the large and small VT trials and after the Paw had fallen to 55–60% of the base-line value. The results suggest that changes in respiratory sensation produced by increasing chemical drive are a consequence of increases in respiratory efferent activity, but a direct effect of changes in PCO2 on respiratory sensation cannot be excluded.

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

1990 ◽  
Vol 69 (2) ◽  
pp. 617-624 ◽  
Author(s):  
K. G. Henke ◽  
J. A. Dempsey ◽  
J. M. Kowitz ◽  
J. B. Skatrud
Keyword(s):  
Airway Resistance ◽  
Minute Ventilation ◽  
Venous Blood ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Esophageal Pressure ◽  
Co2 Partial Pressure ◽  
Upper Airway Resistance ◽  
End Tidal ◽  
End Tidal Co2

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)

Adenosine infusion and periodic breathing during sleep

1992 ◽  
Vol 72 (3) ◽  
pp. 1004-1009 ◽  
Author(s):  
K. Gleeson ◽  
C. W. Zwillich
Keyword(s):  
Ventilatory Response ◽  
Correlation Coefficients ◽  
Periodic Breathing ◽  
Normal Subjects ◽  
Adenosine Infusion ◽  
Amplitude Maximum ◽  
The Mean ◽  
End Tidal ◽  
End Tidal Co2 ◽  
Ventilatory Response To Co2

Intravenously administered adenosine may increase ventilation (VI) and the ventilatory response to CO2 (HCVR). Inasmuch as we have previously hypothesized that those with higher HCVR may be more prone to periodic breathing during sleep, we measured VI and HCVR and monitored ventilatory pattern in seven healthy subjects before and during an infusion of adenosine (80 micrograms.kg-1.min-1) during uninterrupted sleep. Adenosine increased the mean sleeping VI (7.6 +/- 0.4 vs. 6.5 +/- 0.4 l/min, P less than 0.05) and decreased mean end-tidal CO2 values (42.4 +/- 1.2 vs. 43.7 +/- 1.0 Torr, P = 0.06, paired t test) during stable breathing. In six of seven subjects, periodic breathing occurred during this infusion. The amplitude (maximum VI--mean VI) and period length of this periodic breathing was variable among subjects and not predicted by baseline HCVR [correlation coefficients (r) = 0.64, P = 0.17 and r = -0.1, P = 0.9, respectively]. Attempts to measure HCVR during adenosine infusion were unsuccessful because of frequent arousals and continued periodic breathing despite hyperoxic hypercapnia. We conclude that adenosine infusion increases VI and produces periodic breathing during sleep in most normal subjects studied.

Effects of sleep state on ventilatory acclimatization to hypoxia in humans

1984 ◽  
Vol 57 (4) ◽  
pp. 1089-1096 ◽  
Author(s):  
A. D. Berssenbrugge ◽  
J. A. Dempsey ◽  
J. B. Skatrud
Keyword(s):  
Eye Movement ◽  
Chronic Hypoxia ◽  
Minute Ventilation ◽  
Barometric Pressure ◽  
Nrem Sleep ◽  
Hypoxic Exposure ◽  
Adult Males ◽  
Sleep State ◽  
Co2 Partial Pressure ◽  
Arterial O2 Saturation

We assessed the influence of sleep state on ventilatory acclimatization to hypoxia. Ventilation, arterial O2 saturation (SaO2), and arterial acid-base status were monitored in healthy adult males during wakefulness, nonrapid-eye-movement (NREM) sleep, and rapid-eye-movement (REM) sleep in normoxia [barometric pressure (PB) = 740 Torr] and over 4 continuous days of hypobaric hypoxia (PB = 455 Torr). The relative hypoventilation observed during sleep compared with wakefulness in normoxia was also observed during all stages of hypoxic acclimatization. The characteristic time-dependent changes associated with acclimatization to chronic hypoxia were similar during wakefulness and all sleep states: 1) arterial CO2 partial pressure (PaCO2) decreased 27–31% by night 4 with approximately half of this fall occurring acutely (0.3–3 h hypoxia); 2) minute ventilation increased progressively with duration of hypoxic exposure including increased levels of hyperventilation throughout the initial night of sleep in hypoxia; 3) SaO2 was lowest acutely and gradually increased coincident with the progressive hyperventilation; and 4) pHa increased acutely and remained unchanged despite additional hyperventilation due to a compensatory reduction in [HCO3-]a. In addition, in the acclimatized subject hyperventilation persisted following acute restoration of normoxia, and this continued hyperventilation was similar in magnitude during both wakefulness and NREM sleep. These results indicate that suprapontine influences on ventilatory control associated with the state of wakefulness are not required in the process of ventilatory acclimatization to chronic hypoxia.

Possible mechanisms of periodic breathing during sleep

1988 ◽  
Vol 64 (3) ◽  
pp. 1000-1008 ◽  
Author(s):  
K. R. Chapman ◽  
E. N. Bruce ◽  
B. Gothe ◽  
N. S. Cherniack
Keyword(s):  
Control System ◽  
Respiratory Control ◽  
Periodic Breathing ◽  
Nrem Sleep ◽  
Loop Gain ◽  
Hypoxic Conditions ◽  
Spontaneous Oscillations ◽  
End Tidal ◽  
Arterial O2 Saturation ◽  
Stage 1

To determine the effect of respiratory control system loop gain on periodic breathing during sleep, 10 volunteers were studied during stage 1-2 non-rapid-eye-movement (NREM) sleep while breathing room air (room air control), while hypoxic (hypoxia control), and while wearing a tight-fitting mask that augmented control system gain by mechanically increasing the effect of ventilation on arterial O2 saturation (SaO2) (hypoxia increased gain). Ventilatory responses to progressive hypoxia at two steady-state end-tidal PCO2 levels and to progressive hypercapnia at two levels of oxygenation were measured during wakefulness as indexes of controller gain. Under increased gain conditions, five male subjects developed periodic breathing with recurrent cycles of hyperventilation and apnea; the remaining subjects had nonperiodic patterns of hyperventilation. Periodic breathers had greater ventilatory response slopes to hypercapnia under either hyperoxic or hypoxic conditions than nonperiodic breathers (2.98 ± 0.72 vs. 1.50 ± 0.39 l.min-1.Torr-1; 4.39 ± 2.05 vs. 1.72 ± 0.86 l.min-1.Torr-1; for both, P less than 0.04) and greater ventilatory responsiveness to hypoxia at a PCO2 of 46.5 Torr (2.07 ± 0.91 vs. 0.87 ± 0.38 l.min-1.% fall in SaO2(-1); P less than 0.04). To assess whether spontaneous oscillations in ventilation contributed to periodic breathing, power spectrum analysis was used to detect significant cyclic patterns in ventilation during NREM sleep. Oscillations occurred more frequently in periodic breathers, and hypercapnic responses were higher in subjects with oscillations than those without. The results suggest that spontaneous oscillations in ventilation are common during sleep and can be converted to periodic breathing with apnea when loop gain is increased.

Diaphragm electrical activity during negative lower torso pressure in quadriplegic men

1981 ◽  
Vol 51 (3) ◽  
pp. 654-659 ◽  
Author(s):  
R. B. Banzett ◽  
G. F. Inbar ◽  
R. Brown ◽  
M. Goldman ◽  
A. Rossier ◽  
...  
Keyword(s):  
Partial Pressure ◽  
Tidal Volume ◽  
Respiratory System ◽  
Afferent Pathways ◽  
Co2 Partial Pressure ◽  
Inspiratory Muscles ◽  
Spinal Lesions ◽  
Diaphragm Electrical Activity ◽  
End Tidal ◽  
End Tidal Co2

We recorded the diaphragm electromyogram (EMG) of quadriplegic men before and during exposure of the lower torso to continuous negative pressure, which caused shortening of the inspiratory muscles by expanding the respiratory system by one tidal volume. The moving-time-averaged diaphragm EMG was larger during expansion of the respiratory system. When we repeated the experiment with subjects who breathed through a mouthpiece, we found qualitatively similar EMG changes and little or no change in tidal volume or end-tidal CO2 partial pressure. When the pressure was applied or removed rapidly, changes in EMG occurred within one or two breaths. Because end-tidal CO2 partial pressure did not increase, and because the response was rapid, we suggest that the response results from proprioceptive, rather than chemoreceptive, reflexes. As most of these men had complete spinal lesions at C6 or C7 the afferent pathways are likely to be vagal or phrenic.

Hypercapnic cerebral vascular reactivity is decreased, in humans, during sleep compared with wakefulness

2003 ◽  
Vol 94 (6) ◽  
pp. 2197-2202 ◽  
Author(s):  
Guy E. Meadows ◽  
Helen M. A. Dunroy ◽  
Mary J. Morrell ◽  
Douglas R. Corfield
Keyword(s):  
Blood Flow ◽  
Vascular Reactivity ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Stage Iii ◽  
Left Middle Cerebral Artery ◽  
Cortical Blood Flow ◽  
Pulsed Doppler Ultrasound ◽  
End Tidal ◽  
Cerebral Vascular

During wakefulness, increases in the partial pressure of arterial CO2 result in marked rises in cortical blood flow. However, during stage III–IV, non-rapid eye movement (NREM) sleep, and despite a relative state of hypercapnia, cortical blood flow is reduced compared with wakefulness. In the present study, we tested the hypothesis that, in normal subjects, hypercapnic cerebral vascular reactivity is decreased during stage III–IV NREM sleep compared with wakefulness. A 2-MHz pulsed Doppler ultrasound system was used to measure the left middle cerebral artery velocity (MCAV; cm/s) in 12 healthy individuals while awake and during stage III–IV NREM sleep. The end-tidal Pco 2(Pet CO2 ) was elevated during the awake and sleep states by regulating the inspired CO2 load. The cerebral vascular reactivity to CO2 was calculated from the relationship between Pet CO2 and MCAV by using linear regression. From wakefulness to sleep, the Pet CO2 increased by 3.4 Torr ( P < 0.001) and the MCAV fell by 11.7% ( P < 0.001). A marked decrease in cerebral vascular reactivity was noted in all subjects, with an average fall of 70.1% ( P = 0.001). This decrease in hypercapnic cerebral vascular reactivity may, at least in part, explain the stage III–IV NREM sleep-related reduction in cortical blood flow.

Lung volume, closing volume, and gas exchange

1982 ◽  
Vol 52 (6) ◽  
pp. 1453-1457 ◽  
Author(s):  
S. C. Morrison ◽  
D. G. Stubbing ◽  
P. V. Zimmerman ◽  
E. J. Campbell
Keyword(s):  
Gas Exchange ◽  
Lung Volume ◽  
Normal Subjects ◽  
Close Correlation ◽  
Closing Volume ◽  
Tidal Breathing ◽  
Co2 Partial Pressure ◽  
Residual Capacity ◽  
End Tidal ◽  
Arterial O2 Saturation

The effect of a voluntary reduction in lung volume on arterial O2 saturation (SaO2) was studied in 10 normal subjects aged 19–63 yr. SaO2 was measured by ear oximetry first during tidal breathing at functional residual capacity, and then during tidal breathing at 380 ml above residual volume. Tidal volume and breathing frequency were kept constant, and end-tidal CO2 partial pressure remained stable or fell in 9 out of 10 subjects. When lung volume was reduced, SaO2 fell by a mean of 1.5% (range 0–3%). Closing volume (CV) was measured by the N2-washout method (mean 0.89 liter, range 0.41–1.44). There was a close correlation between CV and the fall in SaO2 (r = 0.867, P = 0.001). Arterial and mixed venous CO2 were measured in one subject; the results indicated some fall in cardiac output following the lung volume change, but this accounted for less than half of the fall in SaO2. The relationship between CV and the lung volume at which tidal breathing occurs is an important determinant of pulmonary gas exchange through its effect on the matching of ventilation to perfusion.

scholarly journals Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects

1998 ◽  
Vol 85 (5) ◽  
pp. 1929-1940 ◽  
Author(s):  
Sonia Meza ◽  
Manuel Mendez ◽  
Michele Ostrowski ◽  
Magdy Younes
Keyword(s):  
Airway Pressure ◽  
Stepwise Regression ◽  
Pressure Support ◽  
Amplification Factor ◽  
Periodic Breathing ◽  
Normal Subjects ◽  
Assisted Ventilation ◽  
The Subject ◽  
Central Apneas ◽  
End Tidal

Assisted ventilation with pressure support (PSV) or proportional assist (PAV) ventilation has the potential to produce periodic breathing (PB) during sleep. We hypothesized that PB will develop when PSV level exceeds the product of spontaneous tidal volume (Vt) and elastance (Vt sp ⋅ E) but that the actual level at which PB will develop [PSV(PB)] will be influenced by the[Formula: see text] (difference between eupneic[Formula: see text] and CO2 apneic threshold) and by ΔRR [response of respiratory rate (RR) to PSV]. We also wished to determine the PAV level at which PB develops to assess inherent ventilatory stability in normal subjects. Twelve normal subjects underwent polysomnography while connected to a PSV/PAV ventilator prototype. Level of assist with either mode was increased in small steps (2–5 min each) until PB developed or the subject awakened. End-tidal [Formula: see text], Vt, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated by respiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from [(ΔPaw + Pmus)/Pmus], where ΔPaw is peak Paw − continuous positive airway pressure. PB with central apneas developed in 11 of 12 subjects on PSV. [Formula: see text]ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small and bidirectional (+1.1 to −3.5 min−1). With use of stepwise regression, PSV(PB) was significantly correlated with Vt sp( P = 0.001), E ( P = 0.00009),[Formula: see text]( P = 0.007), and ΔRR ( P = 0.006). The final regression model was as follows: PSV(PB) = 11.1 Vt sp + 0.3E − 0.4 [Formula: see text] − 0.34 ΔRR − 3.4 ( r = 0.98). PB developed in five subjects on PAV at amplification factors of 1.5–3.4. It failed to occur in seven subjects, despite PAF of up to 7.6. We conclude that 1) a[Formula: see text] apneic threshold exists during sleep at 1.5–5.8 Torr below eupneic[Formula: see text], 2) the development of PB during PSV is entirely predictable during sleep, and 3) the inherent susceptibility to PB varies considerably among normal subjects.

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