scholarly journals Episodic hypoxia induces long-term facilitation of upper airway muscle activity in spontaneously breathing anaesthetized rats

2009 ◽  
Vol 587 (13) ◽  
pp. 3329-3342 ◽  
Author(s):  
Stephen Ryan ◽  
Philip Nolan
Keyword(s):  
Muscle Activity ◽  
Upper Airway ◽  
Episodic Hypoxia ◽  
Anaesthetized Rats ◽  
Spontaneously Breathing ◽  
Long Term Facilitation

No evidence for long-term facilitation after episodic hypoxia in spontaneously breathing, anesthetized rats

2000 ◽  
Vol 89 (4) ◽  
pp. 1345-1351 ◽  
Author(s):  
Patrick L. Janssen ◽  
Ralph F. Fregosi
Keyword(s):  
Esophageal Pressure ◽  
Tongue Muscle ◽  
Ventilatory Drive ◽  
Episodic Hypoxia ◽  
Tongue Movements ◽  
Motoneuron Activity ◽  
Spontaneously Breathing ◽  
Long Term Facilitation ◽  
Inspired Oxygen

Repeated electrical or hypoxic stimulation of peripheral chemoreceptors has been shown to cause a persistent poststimulus increase in respiratory motoneuron activity, termed long-term facilitation (LTF). LTF after episodic hypoxia has been demonstrated most consistently in anesthetized, vagotomized, paralyzed, artificially ventilated rats. Evidence for LTF in spontaneously breathing animals and humans after episodic hypoxia is equivocal and may have been influenced by the awake state of the subjects in these studies. The present study was designed to test the hypothesis that LTF is evoked in respiratory-related tongue muscle and inspiratory pump muscle activities after episodic hypoxia in 10 spontaneously breathing, anesthetized, vagotomized rats. The animals were exposed to three (5-min) episodes of isocapnic hypoxia, separated by 5 min of hyperoxia (50% inspired oxygen). Genioglossus, hyoglossus, and inspiratory intercostal EMG activities, along with respiratory-related tongue movements and esophageal pressure, were recorded before, during, and for 60 min after the end of episodic isocapnic hypoxia. We found no evidence for LTF in tongue muscle (genioglossus, hyoglossus) or inspiratory pump muscle (inspiratory intercostal) activities after episodic hypoxia. Rather, the primary poststimulus effect of episodic hypoxia was diminished respiratory frequency, which contributed to a reduction in ventilatory drive.

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.

Episodic hypoxia induces long-term facilitation of neural drive to tongue protrudor and retractor muscles

2005 ◽  
Vol 98 (5) ◽  
pp. 1761-1767 ◽  
Author(s):  
D. D. Fuller
Keyword(s):  
Upper Airway ◽  
Male Rats ◽  
Potential Contribution ◽  
Motor Axons ◽  
Nerve Branch ◽  
Airway Patency ◽  
Pharyngeal Airway ◽  
Episodic Hypoxia ◽  
Long Term Facilitation

Hypoxic episodes can evoke a prolonged augmentation of inspiratory motor output called long-term facilitation (LTF). Hypoglossal (XII) LTF has been assumed to represent increased tongue protrudor muscle activation and pharyngeal airway dilation. However, recent studies indicate that tongue protrudor and retractor muscles are coactivated during inspiration, a behavior that promotes upper airway patency by reducing airway compliance. These experiments tested the hypothesis that XII LTF is manifest as increased inspiratory drive to both tongue protrudor and retractor muscles. Neurograms were recorded in the medial XII nerve branch (XIIMED; contains tongue protrudor motor axons), the lateral XII nerve branch (XIILAT; contains tongue retractor motor axons), and the phrenic nerve in anesthetized, vagotomized, paralyzed, ventilated male rats. Strict isocapnia was maintained for 60 min after five 3-min hypoxic episodes (arterial Po2 = 35 ± 2 Torr) or sham treatment. Peak inspiratory burst amplitude showed a persistent increase in XIIMED, XIILAT, and phrenic nerves during the hour after episodic hypoxia ( P < 0.05 vs. sham). This effect was present regardless of the quantification method (e.g., % baseline vs. percent maximum); however, comparisons of the relative magnitude of LTF between neurograms (e.g., XIIMED vs. XIILAT) varied with the normalization procedure. There was no persistent effect of episodic hypoxia on inspiratory burst frequency ( P > 0.05 vs. sham). These data demonstrate that episodic hypoxia induces LTF of inspiratory drive to both tongue protrudor and retractor muscles and underscore the potential contribution of tongue muscle coactivation to regulation of upper airway patency.

Exposure to intermittent hypoxia and sustained hypercapnia reduces therapeutic CPAP in participants with obstructive sleep apnea

2017 ◽  
Vol 123 (4) ◽  
pp. 993-1002 ◽  
Author(s):  
Mohamad El-Chami ◽  
Sukhesh Sudan ◽  
Ho-Sheng Lin ◽  
Jason H. Mateika
Keyword(s):  
Sleep Apnea ◽  
Muscle Activity ◽  
Airway Pressure ◽  
Intermittent Hypoxia ◽  
Positive Airway Pressure ◽  
Upper Airway ◽  
Flow Limitation ◽  
Long Term Facilitation ◽  
Therapeutic Pressure

Our purpose was to determine whether exposure to mild intermittent hypoxia leads to a reduction in the therapeutic continuous positive airway pressure required to eliminate breathing events. Ten male participants were treated with twelve 2-min episodes of hypoxia ([Formula: see text] ≈50 mmHg) separated by 2-min intervals of normoxia in the presence of [Formula: see text] that was sustained 3 mmHg above baseline. During recovery from the last episode, the positive airway pressure was reduced in a stepwise fashion until flow limitation was evident. The participants also completed a sham protocol under normocapnic conditions, which mimicked the time frame of the intermittent hypoxia protocol. After exposure to intermittent hypoxia, the therapeutic pressure was significantly reduced (i.e., 5 cmH2O) without evidence of flow limitation (103.4 ± 6.3% of baseline, P = 0.5) or increases in upper airway resistance (95.6 ± 15.0% of baseline, P = 0.6). In contrast, a similar decrease in pressure was accompanied by flow limitation (77.0 ± 1.8% of baseline, P = 0.001) and an increase in upper airway resistance (167.2 ± 17.5% of baseline, P = 0.01) after the sham protocol. Consistent with the initiation of long-term facilitation of upper airway muscle activity, exposure to intermittent hypoxia reduced the therapeutic pressure required to eliminate apneic events that could improve treatment compliance. This possibility, coupled with the potentially beneficial effects of intermittent hypoxia on comorbidities linked to sleep apnea, suggests that mild intermittent hypoxia may have a multipronged therapeutic effect on sleep apnea. NEW & NOTEWORTHY Our new finding is that exposure to mild intermittent hypoxia reduced the therapeutic pressure required to treat sleep apnea. These findings are consistent with previous results, which have shown that long-term facilitation of upper muscle activity can be initiated following exposure to intermittent hypoxia in humans.

scholarly journals Selected Contribution: Phrenic long-term facilitation requires 5-HT receptor activation during but not following episodic hypoxia

2001 ◽  
Vol 90 (5) ◽  
pp. 2001-2006 ◽  
Author(s):  
D. D. Fuller ◽  
A. G. Zabka ◽  
T. L. Baker ◽  
G. S. Mitchell
Keyword(s):  
Receptor Antagonist ◽  
Phrenic Nerve ◽  
Receptor Activation ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Sprague Dawley Rats ◽  
Episodic Hypoxia ◽  
Baseline Levels ◽  
Long Term Facilitation

Episodic hypoxia evokes a sustained augmentation of respiratory motor output known as long-term facilitation (LTF). Phrenic LTF is prevented by pretreatment with the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin. We tested the hypothesis that 5-HT receptor activation is necessary for the induction but not maintenance of phrenic LTF. Peak integrated phrenic nerve activity (∫Phr) was monitored for 1 h after three 5-min episodes of isocapnic hypoxia (arterial Po 2 = 40 ± 2 Torr; 5-min hyperoxic intervals) in four groups of anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats [ 1) control ( n = 11), 2) ketanserin pretreatment (2 mg/kg iv; n = 7), and ketanserin treatment 0 and 45 min after episodic hypoxia ( n = 7 each)]. Ketanserin transiently decreased ∫Phr, but it returned to baseline levels within 10 min. One hour after episodic hypoxia, ∫Phr was significantly elevated from baseline in control and in the 0- and 45-min posthypoxia ketanserin groups. Conversely, ketanserin pretreatment abolished phrenic LTF. We conclude that 5-HT receptor activation is necessary to initiate (during hypoxia) but not maintain (following hypoxia) phrenic LTF.

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