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.

A volume-dependent apneic threshold during NREM sleep in the dog

1994 ◽  
Vol 76 (6) ◽  
pp. 2315-2325 ◽  
Author(s):  
C. M. Chow ◽  
L. Xi ◽  
C. A. Smith ◽  
K. W. Saupe ◽  
J. A. Dempsey
Keyword(s):  
Eye Movement ◽  
Nrem Sleep ◽  
Inspiratory Effort ◽  
Central Apnea ◽  
Arterial Pco2 ◽  
Airway Occlusion ◽  
Vagal Blockade ◽  
Minor Contribution ◽  
Per Se ◽  
End Tidal

We determined the causes of central apnea that commonly follow the hyperpnea resulting from brief airway occlusion during non-rapid-eye-movement (NREM) sleep. Ventilation and end-tidal gases were measured before, during, and after 214 trials of 15–20 s of tracheal occlusion in three dogs during NREM sleep. Airway occlusion was accompanied by progressive increases in inspiratory effort and was followed by transient one- to four-breath hyperapneas, with subsequent central apnea [3–15 times eupneic control expiratory duration (TE)] in 62% of occlusion trials. Significant TE prolongation after hyperventilation did not occur until tidal volume (VT) was three times greater than control; i.e., there was a volume-dependent apneic threshold. Transient electroencephalogram arousal at the end of the occlusion often augmented VT, thereby contributing to the subsequent central apnea; however, arousal was not required for the apnea to occur. Significant transient hypocapnia (up to -12 Torr arterial PCO2) commonly occurred after release of airway occlusion but was not closely correlated with the length of central apnea. During vagal blockade, after release of airway occlusion, significant transient hyperventilation occurred but at VT < 40% greater than control, and TE prolongation was markedly reduced. In summary, after release of airway occlusion in NREM sleep, 1) VT greater than three times eupnea was necessary to cause central apnea, 2) transient arousal at the termination of airway occlusion caused longer apneas by augmenting VT, and 3) transient hypocapnia per se made a significant but minor contribution to the postocclusion central apnea.

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+].

Effects of rapid-eye-movement sleep on the apneic threshold in dogs

1993 ◽  
Vol 75 (3) ◽  
pp. 1129-1139 ◽  
Author(s):  
L. Xi ◽  
C. A. Smith ◽  
K. W. Saupe ◽  
K. S. Henderson ◽  
J. A. Dempsey
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Breathing Pattern ◽  
Nrem Sleep ◽  
Inhibitory Response ◽  
Rapid Eye Movement ◽  
Central Apnea ◽  
Fourfold Increase ◽  
Control Value ◽  
End Tidal

We determined whether the apneic threshold after active hyperventilation was different in rapid-eye-movement (REM) vs. non-REM (NREM) sleep. Sleeping dogs were repeatedly exposed to 35–45 s of hypoxia of varying severity (end-tidal PO2 40–60 Torr) that was abruptly terminated with 100% O2. Changes in breathing pattern after brief hypoxia were compared with those after a normoxia-to-hyperoxia transition, i.e., control conditions. In NREM sleep, hypoxic hyperventilation was consistently followed by central apnea, the duration of which was linearly related to the corresponding hypocapnia and/or increase in tidal volume (VT) during hypoxia. After hypoxia, expiratory duration averaged 3.5 x control value at -5-Torr change in end-tidal PCO2 and twofold increase in VT; mean expiratory duration was 5 x control value at -10-Torr change in end-tidal PCO2 and fourfold increase in VT. In REM sleep, central apnea of varying duration did occur on occasion after brief hypoxic hyperventilation, but there was no systematic relationship with magnitude of hypocapnia or increase in VT. Breathing pattern during or after hypoxia in REM was not related to temporal changes in either eye movement density or electroencephalogram frequency. Thus, in contrast to NREM sleep, in REM sleep ("phasic" or "tonic") a posthyperventilation apneic threshold was not present. We attribute this effect of REM to 1) a reduced VT response to hypoxia that would minimize inhibitory "memory" effect from lung stretch and 2) attenuated inhibitory response to any given magnitude of hypocapnia or increased VT. Active hyperventilation-induced apneic threshold may be "masked" by actions of nonchemoreceptor and nonmechanoreceptor inputs affecting respiratory motor output in REM sleep. These data are consistent with the relative absence of central apnea and periodic breathing in humans in REM sleep.

scholarly journals Vagal feedback in the entrainment of respiration to mechanical ventilation in sleeping humans

2000 ◽  
Vol 89 (2) ◽  
pp. 760-769 ◽  
Author(s):  
Peggy M. Simon ◽  
Alfred M. Habel ◽  
J. Andrew Daubenspeck ◽  
J. C. Leiter
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Rate ◽  
Eye Movement ◽  
Lung Transplant ◽  
Respiratory Activity ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
The Other ◽  
Absolute Requirement ◽  
Striking Contrast

We studied the capacity of four “normal” and six lung transplant subjects to entrain neural respiratory activity to mechanical ventilation. Two transplant subjects were studied during wakefulness and demonstrated entrainment indistinguishable from that of normal awake subjects. We studied four normal subjects and four lung transplant subjects during non-rapid eye movement (NREM) sleep. Normal subjects entrained to mechanical ventilation over a range of ventilator frequencies that were within ±3–5 breaths of the spontaneous respiratory rate of each subject. After lung transplantation, during which the vagi were cut, subjects did demonstrate entrainment during NREM sleep; however, entrainment only occurred at ventilator frequencies at or above each subject's spontaneous respiratory rate, and entrainment was less effective. We conclude that there is no absolute requirement for vagal feedback to induce entrainment in subjects, which is in striking contrast to anesthetized animals in which vagotomy uniformly abolishes entrainment. On the other hand, vagal feedback clearly enhances the fidelity of entrainment and extends the range of mechanical frequencies over which entrainment can occur.

Arousal and breathing responses to airway occlusion in healthy sleeping adults

1983 ◽  
Vol 55 (4) ◽  
pp. 1113-1119 ◽  
Author(s):  
F. G. Issa ◽  
C. E. Sullivan
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Progressive Increase ◽  
Total Occlusion ◽  
Airway Occlusion ◽  
Constant Bias ◽  
Bias Flow ◽  
Shallow Breathing

The arousal and breathing responses to total airway occlusion during sleep were measured in 12 normal subjects (7 males and 5 females) aged 25-36 yr. Subjects slept while breathing through a specially designed nosemask, which was glued to the nose with medical-grade silicon rubber. The lips were sealed together with a thin layer of Silastic. The nosemask was attached to a wide-bore (20 mm ID) rigid tube to allow a constant-bias flow of room air from a blower. Total airway occlusion was achieved by simultaneously inflating two rubber balloons fixed in the inspiratory and expiratory pipes. A total of 39 tests were done in stage III/IV nonrapid-eye movement (NREM) sleep in 11 subjects and 10 tests in rapid-eye-movement (REM) sleep in 5 subjects. The duration of total occlusion tolerated before arousal from NREM sleep varied widely (range 0.9-67.0 s) with a mean duration of 20.4 +/- 2.3 (SE) s. The breathing response to occlusion in NREM sleep was characterised by a breath-by-breath progressive increase in suction pressure achieved by an increase in the rate of inspiratory pressure generation during inspiration. In contrast, during REM sleep, arousal invariably occurred after a short duration of airway occlusion (mean duration 6.2 +/- 1.2 s, maximum duration 11.8 s), and the occlusion induced a rapid shallow breathing pattern. Our results indicate that total nasal occlusion during sleep causes arousal with the response during REM sleep being more predictable and with a generally shorter latency than that in NREM sleep.

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.

Apnea after normocapnic mechanical ventilation during NREM sleep

1994 ◽  
Vol 77 (5) ◽  
pp. 2079-2085 ◽  
Author(s):  
A. M. Leevers ◽  
P. M. Simon ◽  
J. A. Dempsey
Keyword(s):  
Mechanical Ventilation ◽  
Nrem Sleep ◽  
Inspiratory Effort ◽  
Control Mechanical Ventilation ◽  
Inhibitory Effects ◽  
Inspiratory Motor ◽  
Ventilator Mode ◽  
Controlled Mechanical Ventilation ◽  
The Subject ◽  
End Tidal

We determined whether normocapnic mechanical ventilation at high tidal volume (VT) and breathing frequency (f) during non-rapid-eye-movement (NREM) sleep would cause apnea. Seven normal sleeping subjects were placed on assist-control mechanical ventilation (i.e., subject initiates inspiration) and VT was gradually increased to 2.1 times eupneic VT (1.17 +/- 0.04 liters). This high VT was maintained for 5 min, the ventilator mode was switched to controlled mechanical ventilation, and f was increased gradually from 9.5 +/- 1.0 (during assist-control mechanical ventilation) to 14.0 +/- 0.7 breaths/min. Normocapnia (end-tidal PCO2 = 44 +/- 1.2 Torr) was maintained throughout the trials. Inspiratory effort was completely inhibited during the period of sustained high VT and f, and apnea occurred immediately after cessation of the passive mechanical ventilation. The duration of the apnea preceding the first inspiratory effort was 20.3 +/- 2.3 s or 7.1 times the eupneic expiratory duration and 5 times the expiratory duration chosen by the subject during assist-control mechanical ventilation. We conclude that inhibition of inspiratory motor output occurs during and after normocapnic mechanical ventilation at high VT and f during NREM sleep. These neuromechanical inhibitory effects may serve to initiate and prolong apnea.

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.

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.

Effect of episodic hypoxia on upper airway mechanics in humans during NREM sleep

2002 ◽  
Vol 92 (6) ◽  
pp. 2565-2570 ◽  
Author(s):  
Mahdi Shkoukani ◽  
Mark A. Babcock ◽  
M. Safwan Badr
Keyword(s):  
Minute Ventilation ◽  
Recovery Period ◽  
Control Period ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Hypoxic Exposure ◽  
Airway Mechanics ◽  
Episodic Hypoxia ◽  
Long Term Facilitation

We hypothesized that long-term facilitation (LTF) is due to decreased upper airway resistance (Rua). We studied 11 normal subjects during stable non-rapid eye movement sleep. We induced brief isocapnic hypoxia (inspired O2fraction = 8%) (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 20 min of recovery (R20) for ventilation, timing, and Rua. In addition, nine subjects were studied in a sham study with no hypoxic exposure. During the episodic hypoxia study, inspiratory minute ventilation (V˙i) increased from 7.1 ± 1.8 l/min during the control period to 8.3 ± 1.8 l/min at R20 (117% of control; P < 0.05). Conversely, there was no change in diaphragmatic electromyogram (EMGdia) between control (16.1 ± 6.9 arbitrary units) and R20 (15.3 ± 4.9 arbitrary units) (95% of control; P > 0.05). In contrast, increasedV˙i was associated with decreased Rua from 10.7 ± 7.5 cmH2O · l−1 · s during control to 8.2 ± 4.4 cmH2O · l−1 · s at R20 (77% of control; P < 0.05). No change was noted in V˙i, Rua, or EMGdia during the recovery period relative to control during the sham study. We conclude the following: 1) increased V˙i in the recovery period is indicative of LTF, 2) the lack of increased EMGdia suggests lack of LTF to the diaphragm, 3) reduced Rua suggests LTF of upper airway dilators, and 4) increased V˙i in the recovery period is due to “unloading” of the upper airway by LTF of upper airway dilators.

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