scholarly journals Intermittent but not sustained hypercapnic hypoxia induces ventilatory long‐term facilitation in awake rats

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Michelle McGuire ◽  
Liming Ling
Keyword(s):  
Hypercapnic Hypoxia ◽  
Long Term Facilitation ◽  
Awake Rats

Long-term facilitation of breathing is absent after episodes of hypercapnic hypoxia in awake humans

2007 ◽  
Vol 156 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Tu Tuan Diep ◽  
Tuba Rashid Khan ◽  
Richard Zhang ◽  
James Duffin
Keyword(s):  
Hypercapnic Hypoxia ◽  
Long Term Facilitation

scholarly journals Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males

2017 ◽  
Vol 123 (3) ◽  
pp. 534-543 ◽  
Author(s):  
Naomi L. Deacon ◽  
R. Doug McEvoy ◽  
Daniel L. Stadler ◽  
Peter G. Catcheside
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Arousal State ◽  
Obstructive Sleep ◽  
Hypercapnic Hypoxia ◽  
Long Term Facilitation ◽  
Healthy Males ◽  
Gas Exposure

Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO2levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO2and 3.0 ± 0.2% O2) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO2, O2saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea.NEW & NOTEWORTHY Both arousal state and concomitant CO2levels are known modulators of the effects of intermittent hypoxia on ventilatory neuroplasticity. This is the first study to investigate the effects of combined intermittent hypercapnic hypoxia during sleep in humans. The lack of neuroplastic effects suggests a need for further studies more closely replicating obstructive sleep apnea to determine the pathophysiological relevance of intermittent hypoxia-induced ventilatory neuroplasticity.

scholarly journals Peripheral chemoreflex contribution to ventilatory long‐term facilitation induced by acute intermittent hypercapnic hypoxia in males and females

2020 ◽  
Vol 598 (20) ◽  
pp. 4713-4730 ◽  
Author(s):  
Tyler D. Vermeulen ◽  
Jenna Benbaruj ◽  
Courtney V. Brown ◽  
Brooke M. Shafer ◽  
John S. Floras ◽  
...  
Keyword(s):  
Hypercapnic Hypoxia ◽  
Males And Females ◽  
Peripheral Chemoreflex ◽  
Long Term Facilitation

Chronic intermittent hypoxia enhances ventilatory long-term facilitation in awake rats

2003 ◽  
Vol 95 (4) ◽  
pp. 1499-1508 ◽  
Author(s):  
Michelle McGuire ◽  
Yi Zhang ◽  
David P. White ◽  
Liming Ling
Keyword(s):  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Freely Behaving ◽  
Long Term Facilitation ◽  
Awake Rats

This study examined the effect of chronic intermittent hypoxia (CIH: 5 min 11-12% O2/5 min air, 12 h/night, 7 nights) on ventilatory long-term facilitation (LTF) and determined the persistence period of this CIH effect in awake rats. LTF, elicited by 5 or 10 episodes of 5 min 12% O2, was measured four times in the same Sprague-Dawley rats by plethysmography, before and 8 h, 3 days, and 7 days after CIH treatment. Resting ventilation was unchanged after CIH. Five episodes of 12% O2 did not initially elicit LTF but elicited LTF (23.5 ± 1.4% above baseline) 8 h after CIH, which partially remained at 3 days (11.4 ± 2.2%, P < 0.05) and disappeared at 7 days. Ten episodes initially elicited LTF (17.7 ± 1.1%, 45-min duration) and elicited an enhanced LTF (29.1 ± 1.5%, 75 min) 8 h after CIH. These results demonstrated that CIH enhanced ventilatory LTF in conscious, freely behaving rats in two ways: 1) a previously ineffective protocol induced LTF; and 2) LTF magnitude was increased and LTF duration prolonged, and this CIH effect on LTF persisted for at least 3 days.

Effect of hypoxic episode number and severity on ventilatory long-term facilitation in awake rats

2002 ◽  
Vol 93 (6) ◽  
pp. 2155-2161 ◽  
Author(s):  
Michelle McGuire ◽  
Yi Zhang ◽  
David P. White ◽  
Liming Ling
Keyword(s):  
Respiratory Activity ◽  
Minute Ventilation ◽  
Severe Hypoxia ◽  
Sprague Dawley ◽  
Hypoxic Episode ◽  
Sprague Dawley Rats ◽  
Episodic Hypoxia ◽  
Long Term Facilitation ◽  
Awake Rats

Episodic hypoxia induces a persistent augmentation of respiratory activity, termed long-term facilitation (LTF). Phrenic LTF saturates in anesthetized animals such that additional episodes of stimulation cause no further increase in LTF magnitude. The present study tested the hypothesis that 1) ventilatory LTF also saturates in awake rats and 2) more severe hypoxia and hypoxic episodes increase the effectiveness of eliciting ventilatory LTF. Minute ventilation was measured in awake, male Sprague-Dawley rats by plethysmography. LTF was elicited by five episodes of 10% O2 poikilocapnic hypoxia (magnitude: 17.3 ± 2.8% above baseline, between 15 and 45 min posthypoxia, duration: 45 min) but not 12 or 8% O2. LTF was also elicited by 10, 20, and 72 episodes of 12% O2(19.1 ± 2.2, 18.9 ± 1.8, and 19.8 ± 1.6%; 45, 60, and 75 min, respectively) but not by three or five episodes. These results show that there is a certain range of hypoxia that induces ventilatory LTF and that additional hypoxic episodes may increase the duration but not the magnitude of this response.

scholarly journals Formation and maintenance of ventilatory long-term facilitation require NMDA but not non-NMDA receptors in awake rats

2008 ◽  
Vol 105 (3) ◽  
pp. 942-950 ◽  
Author(s):  
Michelle McGuire ◽  
Chun Liu ◽  
Ying Cao ◽  
Liming Ling
Keyword(s):  
Nmda Receptors ◽  
Serotonin Receptor ◽  
Nmda Antagonist ◽  
Sprague Dawley ◽  
Receptor Antagonism ◽  
Sprague Dawley Rats ◽  
Episodic Hypoxia ◽  
Long Term Facilitation ◽  
Awake Rats

N-methyl-d-aspartate (NMDA) receptor antagonism in the phrenic motonucleus area eliminates phrenic long-term facilitation (pLTF; a persistent augmentation of phrenic nerve activity after episodic hypoxia) in anesthetized rats. However, whether NMDA antagonism can eliminate ventilatory LTF (vLTF) in awake rats is unclear. The role of non-NMDA receptors in LTF is also unknown. Serotonin receptor antagonism before, but not after, episodic hypoxia eliminates pLTF, suggesting that serotonin receptors are required for induction, but not maintenance, of pLTF. However, because NMDA and non-NMDA ionotropic glutamate receptors are directly involved in mediating the inspiratory drive to phrenic, hypoglossal, and intercostal motoneurons, we hypothesized that these receptors are required for both formation and maintenance of vLTF. vLTF, induced by five episodes of 5-min poikilocapnic hypoxia (10% O2) with 5-min normoxia intervals, was measured with plethysmography in conscious adult male Sprague-Dawley rats. Either (±)-2-amino-5-phosphonovaleric acid (APV; NMDA antagonist, 1.5 mg/kg) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; non-NMDA antagonist, 10 mg/kg) was systemically (ip) injected ∼30 min before hypoxia. APV was also injected immediately after or 20 min after episodic hypoxia in additional groups. As control, vehicle was similarly injected in each rat 1–2 days before. Regardless of being injected before or after episodic hypoxia, vehicle did not alter vLTF (∼23%), whereas APV eliminated vLTF while having little effect on baseline ventilation or hypoxic ventilatory response. In contrast, CNQX enhanced vLTF (∼34%) while decreasing baseline ventilation. Collectively, these results suggest that activation of NMDA but not non-NMDA receptors is necessary for formation and maintenance of vLTF in awake rats.

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