scholarly journals Determinants of long-term facilitation in humans during NREM sleep

2003 ◽  
Vol 94 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Mark Babcock ◽  
Mahdi Shkoukani ◽  
Salah E. Aboubakr ◽  
M. Safwan Badr
Keyword(s):  
Minute Ventilation ◽  
Linear Regression Analysis ◽  
Recovery Period ◽  
Control Period ◽  
Inspiratory Flow ◽  
Flow Limitation ◽  
Peripheral Chemoreceptor ◽  
Long Term Facilitation ◽  
Independent Determinant

Long-term facilitation (LTF) is a prolonged increase in ventilatory motor output after episodic peripheral chemoreceptor stimulation. We have previously shown that LTF is activated during sleep following repetitive hypoxia in snorers (Babcock MA and Badr MS. Sleep 21: 709–716, 1998). The purpose of this study was 1) to ascertain the relative contribution of inspiratory flow limitation to the development of LTF and 2) to determine the effect of eliminating inspiratory flow limitation by nasal CPAP on LTF. We studied 25 normal subjects during stable non-rapid eye movement sleep. We induced 10 episodes of brief repetitive isocapnic hypoxia (inspired O2 fraction = 8%; 3 min) followed by 5 min of room air. Measurements were obtained during control and at 20 min of recovery (R20). During the episodic hypoxia study, inspiratory minute ventilation (V˙i) increased from 6.7 ± 1.9 l/min during the control period to 8.2 ± 2.7 l/min at R20 (122% of control; P < 0.05). Linear regression analysis confirmed that inspiratory flow limitation during control was the only independent determinant of the presence of LTF ( P = 0.005). Six subjects were restudied by using nasal continuous positive airway pressure to ascertain the effect of eliminating inspiratory flow limitation on LTF.V˙i during the recovery period was 97 ± 10% ( P > 0.05). In conclusion, 1) repetitive hypoxia in sleeping humans is followed by increasedV˙i in the recovery period, indicative of development of LTF; 2) inspiratory flow limitation is the only independent determinant of posthypoxic LTF in sleeping human; 3) elimination of inspiratory flow limitation abolished the ventilatory manifestations of LTF; and 4) we propose that increased V˙i in the recovery period was a result of preferential recruitment of upper airway dilators by repetitive hypoxia.

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.

Effect of age on long-term facilitation and chemosensitivity during NREM sleep

2015 ◽  
Vol 119 (10) ◽  
pp. 1088-1096 ◽  
Author(s):  
Susmita Chowdhuri ◽  
Sukanya Pranathiageswaran ◽  
Rene Franco-Elizondo ◽  
Arunima Jayakar ◽  
Arwa Hosni ◽  
...  
Keyword(s):  
Young Adults ◽  
Minute Ventilation ◽  
Recovery Period ◽  
Nrem Sleep ◽  
Elderly Adults ◽  
Healthy Elderly ◽  
Respiratory Plasticity ◽  
Central Apneas ◽  
Long Term Facilitation

The reason for increased sleep-disordered breathing with a predominance of central apneas in the elderly is unknown. We speculate that ventilatory control instability may provide a link between aging and the onset of unstable breathing during sleep. We sought to investigate potential underlying mechanisms in healthy, elderly adults during sleep. We hypothesized that there is 1) a decline in respiratory plasticity or long-term facilitation (LTF) of ventilation and/or 2) increased ventilatory chemosensitivity in older adults during non-, this should be hyphenated, non-rapid rapid eye movement (NREM) sleep. Fourteen elderly adults underwent 15, 1-min episodes of isocapnic hypoxia (EH), nadir O2saturation: 87.0 ± 0.8%. Measurements were obtained during control, hypoxia, and up to 20 min of recovery following the EH protocol, respectively, for minute ventilation (VI), timing, and inspiratory upper-airway resistances (RUA). The results showed the following. 1) Compared with baseline, there was a significant increase in VI(158 ± 11%, P < 0.05) during EH, but this was not accompanied by augmentation of VIduring the successive hypoxia trials nor in VIduring the recovery period (94.4 ± 3.5%, P = not significant), indicating an absence of LTF. There was no change in inspiratory RUAduring the trials. This is in contrast to our previous findings of respiratory plasticity in young adults during sleep. Sham studies did not show a change in any of the measured parameters. 2) We observed increased chemosensitivity with increased isocapnic hypoxic ventilatory response and hyperoxic suppression of VIin older vs. young adults during NREM sleep. Thus increased chemosensitivity, unconstrained by respiratory plasticity, may explain increased periodic breathing and central apneas in elderly adults during NREM sleep.

Long-term facilitation of ventilation and genioglossus muscle activity is evident in the presence of elevated levels of carbon dioxide in awake humans

2006 ◽  
Vol 291 (4) ◽  
pp. R1111-R1119 ◽  
Author(s):  
Daniel P. Harris ◽  
Arvind Balasubramaniam ◽  
M. Safwan Badr ◽  
Jason H. Mateika
Keyword(s):  
Carbon Dioxide ◽  
Muscle Activity ◽  
Control Experiment ◽  
Minute Ventilation ◽  
Recovery Period ◽  
Genioglossus Muscle ◽  
Healthy Humans ◽  
Episodic Hypoxia ◽  
Long Term Facilitation

We hypothesized that long-term facilitation (LTF) of minute ventilation and peak genioglossus muscle activity manifests itself in awake healthy humans when carbon dioxide is sustained at elevated levels. Eleven subjects completed two trials. During trial 1, baseline carbon dioxide levels were maintained during and after exposure to eight 4-min episodes of hypoxia. During trial 2, carbon dioxide was sustained 5 mmHg above baseline levels during exposure to episodic hypoxia. Seven subjects were exposed to sustained elevated levels of carbon dioxide in the absence of episodic hypoxia, which served as a control experiment. Minute ventilation was measured during trial 1, trial 2, and the control experiment. Peak genioglossus muscle activity was measured during trial 2. Minute ventilation during the recovery period of trial 1 was similar to baseline (9.3 ± 0.5 vs. 9.2 ± 0.7 l/min). Likewise, minute ventilation remained unchanged during the control experiment (beginning vs. end of control experiment, 14.4 ± 1.7 vs. 14.7 ± 1.4 l/min). In contrast, minute ventilation and peak genioglossus muscle activity during the recovery period of trial 2 was greater than baseline (minute ventilation: 28.4 ± 1.7 vs. 19.6 ± 1.0 l/min, P < 0.001; peak genioglossus activity: 1.6 ± 0.3 vs. 1.0 fraction of baseline, P < 0.001). We conclude that exposure to episodic hypoxia is necessary to induce LTF of minute ventilation and peak genioglossus muscle activity and that LTF is only evident in awake humans in the presence of sustained elevated levels of carbon dioxide.

Long-term facilitation in obstructive sleep apnea patients during NREM sleep

2001 ◽  
Vol 91 (6) ◽  
pp. 2751-2757 ◽  
Author(s):  
Salah E. Aboubakr ◽  
Amy Taylor ◽  
Reason Ford ◽  
Sarosh Siddiqi ◽  
M. Safwan Badr
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Recovery Period ◽  
Upper Airway ◽  
Flow Limitation ◽  
Inspiratory Time ◽  
Nasal Cpap ◽  
Obstructive Sleep ◽  
Long Term Facilitation

Repetitive hypoxia followed by persistently increased ventilatory motor output is referred to as long-term facilitation (LTF). LTF is activated during sleep after repetitive hypoxia in snorers. We hypothesized that LTF is activated in obstructive sleep apnea (OSA) patients. Eleven subjects with OSA (apnea/hypopnea index = 43.6 ± 18.7/h) were included. Every subject had a baseline polysomnographic study on the appropriate continuous positive airway pressure (CPAP). CPAP was retitrated to eliminate apnea/hypopnea but to maintain inspiratory flow limitation (sham night). Each subject was studied on 2 separate nights. These two studies are separated by 1 mo of optimal nasal CPAP treatment for a minimum of 4–6 h/night. The device was capable of covert pressure monitoring. During night 1 (N1), study subjects used nasal CPAP at suboptimal pressure to have significant air flow limitation (>60% breaths) without apneas/hypopneas. After stable sleep was reached, we induced brief isocapnic hypoxia [inspired O2 fraction (Fi O2 ) = 8%] (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 5, 20, and 40 min of recovery for ventilation, timing ( n = 11), and supraglottic pressure ( n = 6). Upper airway resistance (Rua) was calculated at peak inspiratory flow. During the recovery period, there was no change in minute ventilation (99 ± 8% of control), despite decreased Rua to 58 ± 24% of control ( P < 0.05). There was a reduction in the ratio of inspiratory time to total time for a breath (duty cycle) (0.5 to 0.45, P < 0.05) but no effect on inspiratory time. During night 2 (N2), the protocol of N1 was repeated. N2 revealed no changes compared with N1 during the recovery period. In conclusion, 1) reduced Rua in the recovery period indicates LTF of upper airway dilators; 2) lack of hyperpnea in the recovery period suggests that thoracic pump muscles do not demonstrate LTF; 3) we speculate that LTF may temporarily stabilize respiration in OSA patients after repeated apneas/hypopneas; and 4) nasal CPAP did not alter the ability of OSA patients to elicit LTF at the thoracic pump muscle.

scholarly journals Impact of intermittent hypoxia on long-term facilitation of minute ventilation and heart rate variability in men and women: do sex differences exist?

2008 ◽  
Vol 104 (6) ◽  
pp. 1625-1633 ◽  
Author(s):  
Harpreet Wadhwa ◽  
Ciprian Gradinaru ◽  
Gregory J. Gates ◽  
M. Safwan Badr ◽  
Jason H. Mateika
Keyword(s):  
Nervous System ◽  
Intermittent Hypoxia ◽  
Parasympathetic Nervous System ◽  
Minute Ventilation ◽  
Recovery Period ◽  
Men And Women ◽  
System Activity ◽  
Nervous System Activity ◽  
Long Term Facilitation

Following exposure to intermittent hypoxia, respiratory motor activity and sympathetic nervous system activity may persist above baseline levels for over an hour. The present investigation was designed to determine whether sustained increases in minute ventilation and sympathovagal (S/V) balance, in addition to sustained depression of parasympathetic nervous system activity (PNSA), were greater in men compared with women following exposure to intermittent hypoxia. Fifteen healthy men and women matched for age, race, and body mass index were exposed to eight 4-min episodes of hypoxia during sustained hypercapnia followed by a 15-min end-recovery period. The magnitude of the increase in minute ventilation during the end-recovery period, compared with baseline, was similar in men and women (men, 1.52 ± 0.03; women, 1.57 ± 0.02 fraction of baseline; P < 0.0001). In contrast, depression of PNSA and increases in S/V balance were evident during the end-recovery period, compared with baseline, in men (PNSA, 0.66 ± 0.06 fraction of baseline, P < 0.0001; S/V balance, 2.8 ± 0.7 fraction of baseline, P < 0.03) but not in women (PNSA, 1.27 ± 0.19 fraction of baseline, P = 0.3; S/V balance, 1.8 ± 0.6 fraction of baseline, P = 0.2). We conclude that a sustained increase in minute ventilation, which is indicative of long-term facilitation, is evident in both men and women following exposure to intermittent hypoxia and that this response is independent of sex. In contrast, sustained alterations in autonomic nervous system activity were evident in men but not in women.

Effect of a single breath of 100% oxygen on respiration in neonates during sleep

1984 ◽  
Vol 57 (5) ◽  
pp. 1531-1535 ◽  
Author(s):  
T. Aizad ◽  
J. Bodani ◽  
D. Cates ◽  
L. Horvath ◽  
H. Rigatto
Keyword(s):  
Gestational Age ◽  
Minute Ventilation ◽  
Control Period ◽  
Full Term ◽  
Preterm Neonates ◽  
Sleep State ◽  
Quiet Sleep ◽  
Peripheral Chemoreceptor ◽  
Term Infants ◽  
Single Breath

To determine the effect of a single breath of 100% O2 on ventilation, 10 full-term [body wt 3,360 +/- 110 (SE) g, gestational age 39 +/- 0.4 wk, postnatal age 3 +/- 0.6 days] and 10 preterm neonates (body wt 2,020 +/- 60 g, gestational age 34 +/- 2 wk, postnatal age 9 +/- 2 days) were studied during active and quiet sleep states. The single-breath method was used to measure peripheral chemoreceptor response. To enhance response and standardize the control period for all infants, fractional inspired O2 concentration was adjusted to 16 +/- 0.6% for a control O2 saturation of 83 +/- 1%. After 1 min of control in each sleep state, each infant was given a single breath of O2 followed by 21% O2. Minute ventilation (VE), tidal volume (VT), breathing frequency (f), alveolar O2 and CO2 tension, O2 saturation (ear oximeter), and transcutaneous O2 tension were measured. VE always decreased with inhalation of O2 (P less than 0.01). In quiet sleep, the decrease in VE was less in full-term (14%) than in preterm (40%) infants (P less than 0.001). Decrease in VE was due primarily to a drop in VT in full-term infants as opposed to a fall in f and VT in preterm infants (P less than 0.05). Apnea, as part of the response, was more prevalent in preterm than in full-term infants. In active sleep the decrease in VE was similar both among full-term (19%) and preterm (21%) infants (P greater than 0.5). These results suggest greater peripheral chemoreceptor response in preterm than in full-term infants, reflected by a more pronounced decrease in VE with O2. The results are compatible with a more powerful peripheral chemoreceptor contribution to breathing in preterm than in full-term infants.

Effect of baseline oxygenation on the ventilatory response to inhaled 100% oxygen in preterm infants

1995 ◽  
Vol 79 (6) ◽  
pp. 2101-2105 ◽  
Author(s):  
A. Z. Haider ◽  
V. Rehan ◽  
S. Al-Saedi ◽  
R. Alvaro ◽  
K. Kwiatkowski ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Ventilatory Response ◽  
Recovery Period ◽  
Control Period ◽  
Periodic Breathing ◽  
Quiet Sleep ◽  
Peripheral Chemoreceptor ◽  
Lower Baseline ◽  
O2 Concentration ◽  
Flow Through

We tested the hypothesis that the immediate (< 1 min) ventilatory response to 100% O2 in preterm infants, a test of peripheral chemoreceptor activity characterized by a decrease in ventilation due to apnea, is more pronounced at lower baseline O2 concentrations. We studied 12 healthy preterm infants [birth weight 1,425 +/- 103 (SE) g; study weight 1,670 +/- 93 g; gestational age 30 +/- 1 wk; postnatal age 27 +/- 7 days] during quiet sleep. The infants inhaled 15, 21, 25, 30, 35, 40, and 45% O2 for 5 min in a randomized manner (control period), followed by 100% O2 for 2 min, and then the same initial O2 concentration again for 2 min (recovery period). A nose piece and a flow-through system were used to measure ventilation. The immediate decrease in ventilation with 100% O2 was 46% on 15% O2, 24% on 21% O2, 11% on 25% O2, 8% on 30% O2, 12% on 35% O2, and 8% on 40% O2; there was no decrease on 45% O2 (P < 0.01). The corresponding mean duration of apnea was 29 s during 15% O2, 18 s during 21% O2, 8 s during 25% O2, 9 s during 30 and 35% O2, and 3 s during 40% O2; only one infant developed a 5-s apnea during 45% O2 (P < 0.001). The findings suggest that 1) the ventilatory decrease in response to 100% O2 is dependent on the baseline oxygenation, being more pronounced the lower the baseline O2 concentration; and 2) this ventilatory decrease is entirely related to more prolonged apneas observed with lower baseline O2 concentrations. We speculate that the peripheral chemoreceptors, being so active in the small preterm infant with relatively low arterial PO2, are highly susceptible to changes in PO2, and this makes them prone to irregular or periodic breathing, especially during sleep.

scholarly journals Compensatory rebound of body movements during sleep, after asphyxia in neonatal rats

2008 ◽  
Vol 23 (3) ◽  
pp. 253-257
Author(s):  
Olivia Adayr Xavier Suarez ◽  
Katsumasa Hoshino
Keyword(s):  
Perinatal Asphyxia ◽  
Recovery Period ◽  
Control Period ◽  
Neonatal Rats ◽  
Newborn Rats ◽  
Body Movements ◽  
Movement Frequency ◽  
Sleep Parameters ◽  
Long Term Consequences

PURPOSE: The usefulness of body movements that occur during sleep when assessing perinatal asphyxia and predicting its long-term consequences is contradictory. This study investigated whether neonatal rats manifest these movements in compensatory rebound after asphyxia, and if these alterations play an important role in its pathogenesis. METHODS: Eight neonatal rats (aged 6-48h) were implanted with small EMG and EKG electrodes and sleep movements were recorded over a 30-minute control period. Recordings were continued during asphyxia caused by the enclosure of the animal in a polyvinyl sheet for 60 minutes, followed by a 30-minute recovery period. RESULTS: Heart rate was lowered to bradycardic level during asphyxia causing behavioral agitation and increased waking time during the initial phase (30 minutes). Sleep-related movements were also significantly reduced from 12.5 ± 0.5 (median ± SE/2min) to 9.0 ± 0.44 in the final half of the period (Anova, p<0.05). Movement frequency increased in the recovery period to 15.0 ± 0.49 (Anova, p<0.05). CONCLUSION: These data show that newborn rats present compensatory rebound of body movements during sleep which may help in the diagnosis of asphyxia and other problems related to sleep parameters.

scholarly journals Effect of episodic hypoxia on the susceptibility to hypocapnic central apnea during NREM sleep

2010 ◽  
Vol 108 (2) ◽  
pp. 369-377 ◽  
Author(s):  
Susmita Chowdhuri ◽  
Irina Shanidze ◽  
Lisa Pierchala ◽  
Daniel Belen ◽  
Jason H. Mateika ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Ventilatory Response ◽  
Recovery Period ◽  
Positive Pressure ◽  
Central Apnea ◽  
Hypoxic Ventilatory Response ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Long Term Facilitation

We hypothesized that episodic hypoxia (EH) leads to alterations in chemoreflex characteristics that might promote the development of central apnea in sleeping humans. We used nasal noninvasive positive pressure mechanical ventilation to induce hypocapnic central apnea in 11 healthy participants during stable nonrapid eye movement sleep before and after an exposure to EH, which consisted of fifteen 1-min episodes of isocapnic hypoxia (mean O2 saturation/episode: 87.0 ± 0.5%). The apneic threshold (AT) was defined as the absolute measured end-tidal Pco2 (PetCO2) demarcating the central apnea. The difference between the AT and baseline PetCO2 measured immediately before the onset of mechanical ventilation was defined as the CO2 reserve. The change in minute ventilation (V̇I) for a change in PetCO2 (ΔV̇I/ ΔPetCO2) was defined as the hypocapnic ventilatory response. We studied the eupneic PetCO2, AT PetCO2, CO2 reserve, and hypocapnic ventilatory response before and after the exposure to EH. We also measured the hypoxic ventilatory response, defined as the change in V̇I for a corresponding change in arterial O2 saturation (ΔV̇I/ΔSaO2) during the EH trials. V̇I increased from 6.2 ± 0.4 l/min during the pre-EH control to 7.9 ± 0.5 l/min during EH and remained elevated at 6.7 ± 0.4 l/min the during post-EH recovery period ( P < 0.05), indicative of long-term facilitation. The AT was unchanged after EH, but the CO2 reserve declined significantly from −3.1 ± 0.5 mmHg pre-EH to −2.3 ± 0.4 mmHg post-EH ( P < 0.001). In the post-EH recovery period, ΔV̇I/ΔPetCO2 was higher compared with the baseline (3.3 ± 0.6 vs. 1.8 ± 0.3 l·min−1·mmHg−1, P < 0.001), indicative of an increased hypocapnic ventilatory response. However, there was no significant change in the hypoxic ventilatory response (ΔV̇I/ΔSaO2) during the EH period itself. In conclusion, despite the presence of ventilatory long-term facilitation, the increase in the hypocapnic ventilatory response after the exposure to EH induced a significant decrease in the CO2 reserve. This form of respiratory plasticity may destabilize breathing and promote central apneas.

Long-term facilitation of ventilation is not present during wakefulness in healthy men or women

2002 ◽  
Vol 93 (6) ◽  
pp. 2129-2136 ◽  
Author(s):  
A. S. Jordan ◽  
P. G. Catcheside ◽  
F. J. O'Donoghue ◽  
R. D. McEvoy
Keyword(s):  
Repeated Measures ◽  
Human Subjects ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Menstrual Phase ◽  
Healthy Human ◽  
Dilator Muscle ◽  
Obstructive Sleep ◽  
Long Term Facilitation

Obstructive sleep apnea (OSA) is more common in men than in women for reasons that are unclear. The stability of the respiratory controller has been proposed to be important in OSA pathogenesis and may be involved in the gender difference in prevalence. Repetitive hypoxia elicits a progressive rise in ventilation in animals [long-term facilitation (LTF)]. There is uncertainty whether LTF occurs in humans, but if present it may stabilize respiration and possibly also the upper airway. This study was conducted to determine 1) whether LTF exists during wakefulness in healthy human subjects and, if so, whether it is more pronounced in women than men and 2) whether inspiratory pump and upper airway dilator muscle activities are affected differently by repetitive hypoxia. Twelve healthy young men and ten women in the luteal menstrual phase were fitted with a nasal mask and intramuscular genioglossal EMG (EMGgg) recording electrodes. After 5 min of rest, subjects were exposed to ten 2-min isocapnic hypoxic periods (∼9% O2 in N2, arterial O2 saturation ∼80%) separated by 2 min of room air. Inspired minute ventilation (V˙i) and peak inspiratory EMGgg activity were averaged over 30-s intervals, and respiratory data were compared between genders during and after repetitive hypoxia by using ANOVA for repeated measures. V˙i during recovery from repetitive hypoxia was not different from the resting level and not different between genders. There was no facilitation of EMGgg activity during or after repetitive hypoxia. EMGgg activity was reduced below baseline during recovery from repetitive hypoxia in women. In conclusion, we have found no evidence of LTF of ventilation or upper airway dilator muscle activity in healthy subjects during wakefulness.

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