Is there a link between intermittent hypoxia-induced respiratory plasticity and obstructive sleep apnoea?

Department of Comparative Biosciences, University of Wisconsin Madison, 2015 Linden Drive, Madison, WI 53706, USA.
Experimental Physiology (Impact Factor: 2.87). 02/2007; 92(1):27-37. DOI: 10.1113/expphysiol.2006.033720
Source: PubMed

ABSTRACT Although neuroplasticity is an important property of the respiratory motor control system, its existence has been appreciated only in recent years and, as a result, its functional significance is not completely understood. The most frequently studied models of respiratory plasticity is respiratory long-term facilitation (LTF) following acute intermittent hypoxia and enhanced LTF following chronic intermittent hypoxia. Since intermittent hypoxia is a prominent feature of sleep-disordered breathing, LTF and/or enhanced LTF may compensate for factors that predispose to sleep-disordered breathing, particularly during obstructive sleep apnoea (OSA). Long-term facilitation has been studied most frequently in rats, and exhibits interesting properties consistent with a role in stabilizing breathing during sleep. Specifically, LTF: (1) is prominent in upper airway respiratory motor activity, suggesting that it stabilizes upper airways and maintains airway patency; (2) is most prominent during sleep in unanaesthetized rats; and (3) exhibits sexual dimorphism (greatest in young male and middle-aged female rats; smallest in middle-aged male and young female rats). Although these features are consistent with the hypothesis that upper airway LTF minimizes the prevalence of OSA in humans, there is little direct evidence for such an effect. Here we review advances in our understanding of LTF and its underlying mechanisms and present evidence concerning a potential role for LTF in maintaining upper airway patency, stabilizing breathing and preventing OSA in humans. Regardless of the relationship between LTF and OSA, a detailed understanding of cellular and synaptic mechanisms that underlie LTF may guide the development of new drugs to regulate upper airway tone, thereby offsetting the tendency for upper airway collapse characteristic of heavy snoring and OSA.

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    ABSTRACT: A major cause of mortality after spinal cord injury is respiratory failure. In normal rats, acute intermittent hypoxia (AIH) induces respiratory motor plasticity, expressed as diaphragm (Dia) and second external intercostal (T2 EIC) long-term facilitation (LTF). Dia (not T2 EIC) LTF is enhanced by systemic adenosine 2A (A2A) receptor inhibition in normal rats. We investigated the respective contributions of Dia and T2 EIC to daily AIH-induced functional recovery of breathing capacity with/without A2A receptor antagonist (KW6002, i.p.) following C2 hemisection (C2HS). Rats received daily AIH (dAIH: 10, 5-min episodes, 10.5% O2; 5-min normoxic intervals; 7 successive days beginning 7days post-C2HS) or daily normoxia (dNx) with/without KW6002, followed by weekly (reminder) presentations for 8weeks. Ventilation and EMGs from bilateral diaphragm and T2 EIC muscles were measured with room air breathing (21% O2) and maximum chemoreceptor stimulation (MCS: 7% CO2, 10.5% O2). dAIH increased tidal volume (VT) in C2HS rats breathing room air (dAIH+vehicle: 0.47±0.02, dNx+vehicle: 0.40±0.01ml/100g; p<0.05) and MCS (dAIH+vehicle: 0.83±0.01, dNx+vehicle: 0.73±0.01ml/100g; p<0.001); KW6002 had no significant effect. dAIH enhanced contralateral (uninjured) diaphragm EMG activity, an effect attenuated by KW6002, during room air breathing and MCS (p<0.05). Although dAIH enhanced contralateral T2 EIC EMG activity during room air breathing, KW6002 had no effect. dAIH had no statistically significant effects on diaphragm or T2 EIC EMG activity ipsilateral to injury. Thus, two weeks post-C2HS: 1) dAIH enhances breathing capacity by effects on contralateral diaphragm and T2 EIC activity; and 2) dAIH-induced recovery is A2A dependent in diaphragm, but not T2 EIC. Daily AIH may be a useful in promoting functional recovery of breathing capacity after cervical spinal injury, but A2A receptor antagonists (e.g. caffeine) may undermine its effectiveness shortly after injury. Copyright © 2015. Published by Elsevier Inc.
    Experimental Neurology 02/2015; 266. DOI:10.1016/j.expneurol.2015.02.007 · 4.62 Impact Factor
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    American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California; 04/2009

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