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

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.

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Peripheral chemoreflex induced long term facilitation of sympathetic nerve activity: Role of adrenomedullin in the rostral ventrolateral medulla

Autonomic Neuroscience ◽

10.1016/j.autneu.2011.05.210 ◽

2011 ◽

Vol 163 (1-2) ◽

pp. 116

Author(s):

D.S.A. Colombari ◽

E. Colombari ◽

D. Murphy ◽

J.F.R. Paton

Keyword(s):

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Rostral Ventrolateral Medulla ◽

Ventrolateral Medulla ◽

Nerve Activity ◽

Peripheral Chemoreflex ◽

Long Term Facilitation

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Tetraplegia is associated with enhanced peripheral chemoreflex sensitivity and ventilatory long-term facilitation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00088.2015 ◽

2015 ◽

Vol 119 (10) ◽

pp. 1183-1193 ◽

Cited By ~ 17

Author(s):

Abdulghani Sankari ◽

Amy T. Bascom ◽

Anas Riehani ◽

M. Safwan Badr

Keyword(s):

Heart Rate ◽

Minute Ventilation ◽

Low Frequency ◽

Time Period ◽

Cord Injury ◽

Chemoreflex Sensitivity ◽

Peripheral Chemoreflex ◽

Long Term Facilitation ◽

Mixed Gases

Cardiorespiratory plasticity induced by acute intermittent hypoxia (AIH) may contribute to recovery following spinal cord injury (SCI). We hypothesized that patients with cervical SCI would demonstrate higher minute ventilation (V̇e) following AIH compared with subjects with thoracic SCI and able-bodied subjects who served as controls. Twenty-four volunteers (8 with cervical SCI, 8 with thoracic SCI, and 8 able-bodied) underwent an AIH protocol during wakefulness. Each subject experienced 15 episodes of isocapnic hypoxia using mixed gases of 100% nitrogen (N2), 8% O2, and 40% CO2to achieve oxygen saturation ≤90% followed by room air (RA). Measurements were obtained before, during, and 40 min after AIH to obtain ventilation and heart rate variability data [R-R interval (RRI) and low-frequency/high-frequency power (LF/HF)]. AIH results were compared with those of sham studies conducted in RA during the same time period. Individuals with cervical SCI had higher V̇e after AIH compared with able-bodied controls (117.9 ± 23.2% vs. 97.9 ± 11.2%, P < 0.05). RRI decreased during hypoxia in all individuals (those with cervical SCI, from 1,009.3 ± 65.0 ms to 750.2 ± 65.0 ms; those with thoracic SCI, from 945.2 ± 65.0 ms to 674.9 ± 65.0 ms; and those who were able-bodied, from 949 ± 75.0 to 682.2 ± 69.5 ms; P < 0.05). LH/HF increased during recovery in individuals with thoracic SCI and those who were able-bodied (0.54 ± 0.22 vs. 1.34 ± 0.22 and 0.67 ± 0.23 vs. 1.82 ± 0.23, respectively; P < 0.05) but remained unchanged in the group with cervical SCI. Our conclusion is that patients with cervical SCI demonstrate ventilatory long-term facilitation following AIH compared with able-bodied controls. Heart rate responses to hypoxia are acutely present in patients with cervical SCI but are absent during posthypoxic recovery.

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