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First published online on November 10, 2006.
Experimental Physiology (2006)
DOI: 10.1113/expphysiol.2006.033720
© The Physiological Society 2006

A more recent version of this article appeared on January 1, 2007
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Received October 9, 2006
Revised October 24, 2006
Accepted after revision November 6, 2006


Respiratory [290]

Is there a Link between Intermittent Hypoxia-Induced Respiratory Plasticity and Obstructive Sleep Apnoea?

Safraaz Mahamed 1 Gordon Mitchell 1*

1 University of Wisconsin

* To whom correspondence should be addressed. E-mail: mitchell{at}svm.vetmed.wisc.edu.


   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 model 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). LTF has been studied most frequently in rats, and exhibits interesting properties consistent with a role in stabilizing breathing during sleep. In specific, 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, 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/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.

Key Words: Plasticity, Respiratory control, Sleep




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