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.

Peripheral chemoreflex responsiveness is increased at elevated levels of carbon dioxide after episodic hypoxia in awake humans

2004 ◽  
Vol 96 (3) ◽  
pp. 1197-1205 ◽  
Author(s):  
Jason H. Mateika ◽  
Chris Mendello ◽  
Dany Obeid ◽  
M. Safwan Badr
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
High Oxygen ◽  
Recruitment Threshold ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Carbon Dioxide Levels ◽  
Peripheral Chemoreflex ◽  
Long Term Facilitation ◽  
Ventilatory Response To Hypoxia

We hypothesized that the acute ventilatory response to hypoxia is enhanced after exposure to episodic hypoxia in awake humans. Eleven subjects completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then breathed from a bag containing normocapnic (42 Torr), low (50 Torr), or high oxygen (140 Torr) gas mixtures. During the trials, PetCO2 increased while a constant oxygen level was maintained. The point at which ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the ventilatory recruitment threshold. The ventilatory response below and above the recruitment threshold was determined. Ventilation did not persist above baseline values immediately after exposure to episodic hypoxia; however, PetCO2 levels were reduced compared with baseline. In contrast, compared with baseline, the ventilatory response to progressive increases in carbon dioxide during rebreathing trials in the presence of low but not high oxygen levels was increased after exposure to episodic hypoxia. This increase occurred when carbon dioxide levels were above but not below the ventilatory recruitment threshold. We conclude that long-term facilitation of ventilation (i.e., increases in ventilation that persist when normoxia is restored after episodic hypoxia) is not expressed in awake humans in the presence of hypocapnia. Nevertheless, despite this lack of expression, the acute ventilatory response to hypoxia in the presence of hypercapnia is increased after exposure to episodic hypoxia.

Selected Contribution: Intermittent hypoxia induces phrenic long-term facilitation in carotid-denervated rats

2003 ◽  
Vol 94 (1) ◽  
pp. 399-409 ◽  
Author(s):  
Ryan W. Bavis ◽  
Gordon S. Mitchell
Keyword(s):  
Detectable Effect ◽  
Sprague Dawley ◽  
Neuron Activation ◽  
Sprague Dawley Rats ◽  
Burst Amplitude ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Inspiratory Activity ◽  
Long Term Facilitation

Episodic hypoxia elicits a long-lasting augmentation of phrenic inspiratory activity known as long-term facilitation (LTF). We investigated the respective contributions of carotid chemoafferent neuron activation and hypoxia to the expression of LTF in urethane-anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats. One hour after three 5-min isocapnic hypoxic episodes [arterial Po 2(PaO2 ) = 40 ± 5 Torr], integrated phrenic burst amplitude was greater than baseline in both carotid-denervated ( n = 8) and sham-operated ( n = 7) rats ( P < 0.05), indicating LTF. LTF was reduced in carotid-denervated rats relative to sham ( P < 0.05). In this and previous studies, rats were ventilated with hyperoxic gas mixtures (inspired oxygen fraction = 0.5) under baseline conditions. To determine whether episodic hyperoxia induces LTF, phrenic activity was recorded under normoxic (PaO2 = 90–100 Torr) conditions before and after three 5-min episodes of isocapnic hypoxia (PaO2 = 40 ± 5 Torr; n = 6) or hyperoxia (PaO2 > 470 Torr; n= 6). Phrenic burst amplitude was greater than baseline 1 h after episodic hypoxia ( P < 0.05), but episodic hyperoxia had no detectable effect. These data suggest that hypoxia per se initiates LTF independently from carotid chemoafferent neuron activation, perhaps through direct central nervous system effects.

The influence of episodic hypoxia on upper airway collapsibility in subjects with obstructive sleep apnea

2007 ◽  
Vol 103 (3) ◽  
pp. 911-916 ◽  
Author(s):  
James A. Rowley ◽  
Ihab Deebajah ◽  
Swapna Parikh ◽  
Ali Najar ◽  
Rajib Saha ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Upper Airway ◽  
Obstructive Sleep ◽  
Airway Collapsibility ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Upper Airway Collapsibility ◽  
Long Term Facilitation

We have previously shown that in subjects with obstructive sleep apnea, repetitive hypoxia is associated with long-term facilitation as manifested by decreased upper airway resistance (Rua). Our objective was to study the influence of long-term facilitation on upper airway collapsibility as measured by the critical closing pressure (Pcrit) model and to determine whether changes in Rua correlated with changes in collapsibility. We studied 13 subjects (10 men, 3 women) with a mean apnea-hypopnea index of 43.9 ± 24.0 events/h. In the first protocol with 11 subjects, we measured collapsibility using a Pcrit protocol before and after episodic hypoxia. Brief (3 min) isocapnic hypoxia (inspired O2 fraction = 8%) followed by 5 min of room air was induced 10 times. A sham study without hypoxia was performed on eight subjects. Ventilatory parameters, Rua, and Pcrit before and after episodic hypoxia were measured. At 20 min of recovery, there was no change in minute ventilation but there was a significant decrease in Rua compared with the control period (control, 8.6 ± 4.8 cmH2O·l−1·s vs. recovery, 5.9 ± 3.8 cmH2O·l−1·s; P < 0.05). However, there was no change in Pcrit between the control (2.3 ± 1.9 cmH2O) and recovery (2.7 ± 3.2 cmH2O) periods. No changes in Rua or Pcrit were observed in the sham protocol. We conclude that long-term facilitation of upper airway dilators is not associated with changes in upper airway collapsibility in subjects with obstructive sleep apnea. These results corroborate previous evidence that changes in upper airway resistance and caliber can be dissociated from changes in upper airway collapsibility.

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.

scholarly journals The magnitude of the hypoxic ventilatory response and ventilatory long‐term facilitation is reduced during sleep when compared to wakefulness

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Ziauddin Syed ◽  
David G. Gerst ◽  
Sanar S. Yokhana ◽  
Kulraj S. Sandhu ◽  
Ho‐Sheng Lin ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Hypoxic Ventilatory Response ◽  
Long Term Facilitation

scholarly journals The hypoxic ventilatory response and ventilatory long-term facilitation are altered by time of day and repeated daily exposure to intermittent hypoxia

2011 ◽  
Vol 110 (1) ◽  
pp. 15-28 ◽  
Author(s):  
David G. Gerst ◽  
Sanar S. Yokhana ◽  
Laura M. Carney ◽  
Dorothy S. Lee ◽  
M. Safwan Badr ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Time Of Day ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Daily Exposure ◽  
Long Term Facilitation

This study examined whether time of day and repeated exposure to intermittent hypoxia have an impact on the hypoxic ventilatory response (HVR) and ventilatory long-term facilitation (vLTF). Thirteen participants with sleep apnea were exposed to twelve 4-min episodes of isocapnic hypoxia followed by a 30-min recovery period each day for 10 days. On days 1 (initial day) and 10 (final day) participants completed the protocol in the evening (PM); on the remaining days the protocol was completed in the morning (AM). The HVR was increased in the morning compared with evening on the initial (AM 0.83 ± 0.08 vs. PM 0.64 ± 0.11 l·min−1·%SaO2−1; P ≤ 0.01) and final days (AM 1.0 ± 0.08 vs. PM 0.81 ± 0.09 l·min−1·%SaO2−1; P ≤ 0.01, where %SaO2 refers to percent arterial oxygen saturation). Moreover, the magnitude of the HVR was enhanced following daily exposure to intermittent hypoxia in the morning (initial day 0.83 ± 0.08 vs. final day 1.0 ± 0.08 l·min−1·%SaO2−1; P ≤ 0.03) and evening (initial day 0.64 ± 0.11 vs. final day 0.81 ± 0.09 l·min−1·%SaO2−1; P ≤ 0.03). vLTF was reduced in the morning compared with the evening on the initial (AM 19.03 ± 0.35 vs. PM 22.30 ± 0.49 l/min; P ≤ 0.001) and final (AM 20.54 ± 0.32 vs. PM 23.11 ± 0.54 l/min; P ≤ 0.01) days. Following daily exposure to intermittent hypoxia, vLTF was enhanced in the morning (initial day 19.03 ± 0.35 vs. final day 20.54 ± 0.32 l/min; P ≤ 0.01). We conclude that the HVR is increased while vLTF is decreased in the morning compared with the evening in individuals with sleep apnea and that the magnitudes of these phenomena are enhanced following daily exposure to intermittent hypoxia.

Ventilatory long-term facilitation is greater in 1- vs. 2-mo-old awake rats

2005 ◽  
Vol 98 (4) ◽  
pp. 1195-1201 ◽  
Author(s):  
Michelle McGuire ◽  
Liming Ling
Keyword(s):  
Ventilatory Response ◽  
Age Groups ◽  
Male Rats ◽  
Chronic Intermittent Hypoxia ◽  
Hypoxic Ventilatory Response ◽  
Conscious Rat ◽  
Adult Rats ◽  
Old Rats ◽  
Long Term Facilitation

Respiratory long-term facilitation (LTF) declines in middle-aged vs. adult male rats. Chronic intermittent hypoxia (CIH; 5 min 11–12% O2/5 min air, 12 h/night, 7 nights) enhances LTF in adult rats. However, LTF in immature rats and the effect of early CIH are unevaluated. The present study compared LTF in 1- and 2-mo-old rats and examined the effect of neonatal CIH (initiated at 2 days after birth) on the LTF. Ventilatory LTF, elicited by 5 ( protocol 1) or 10 ( protocol 2) episodes of poikilocapnic hypoxia (5 min 12% O2/5 min air), was measured twice by plethysmography on the same male conscious rat when it was 1 and 2 mo old. In untreated (without CIH) rats, both resting ventilation (54.7 ± 0.6 vs. 43.0 ± 0.2 ml·100 g−1·min−1) and hypoxic ventilatory response (131 ± 4 vs. 66 ± 3% above baseline) were greater in 1- vs. 2-mo-old rats. Protocol 1 elicited LTF in 1-mo-old (12.5 ± 1.0% above baseline) but not 2-mo-old rats. Protocol 2 elicited a greater LTF in 1-mo-old (24.3 ± 0.8%) vs. 2-mo-old rats (18.2 ± 0.5%). In CIH-treated rats, protocol 1 also elicited LTF in 1-mo-old (13.1 ± 1.5%) but not 2-mo-old rats. Protocol 2 elicited LTF in both age groups, but LTF was enhanced by the CIH only in 1-mo-old rats (28.8 ± 0.9%). These results suggest that ventilatory LTF and hypoxic ventilatory response are greater in male rats shortly before their sexual maturity and that the neonatal CIH somewhat enhances ventilatory LTF ∼3 wk after CIH, but this enhancement does not last to adulthood.

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