Mechanisms of Apnea

Harvard University, Cambridge, Massachusetts, United States
Progress in cardiovascular diseases (Impact Factor: 4.25). 02/2009; 51(4):313-23. DOI: 10.1016/j.pcad.2008.02.003
Source: PubMed


This paper focuses on the underlying mechanisms contributing to sleep-disordered breathing. Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is characterized by repetitive narrowing or collapse of the pharyngeal airway during sleep. Conversely, central sleep apnea (CSA), highly prevalent in congestive heart failure, is distinguished by a lack of drive to breathe during sleep, resulting in repetitive periods of insufficient ventilation. Both lead to compromised gas exchange, impaired sleep continuity, and catecholamine surges and are associated with major comorbidities including excessive daytime sleepiness and increased risk of cardiovascular disease. Although OSA and CSA exist on a spectrum of sleep-disordered breathing, the 2 entities may overlap in their underlying pathophysiologies. This brief review summarizes the etiology and current understanding of OSA and CSA pathophysiology and the role that the cardiovascular system may play in contributing to disease pathology and highlights the likely substantial overlap that exists between the various forms of sleep-disordered breathing.

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    • "The contribution of central apneas in patients with ACS may be underestimated. It should also be noted that central apneas can be induced by severe obstructive events [Eckert et al., 2009; Salloum et al., 2010]. "
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    ABSTRACT: Auriculocondylar syndrome (ACS) is a branchial arch syndrome typically inherited in an autosomal dominant fashion. Patients with ACS display the following core symptoms with varying severity: a specific malformation of the external ear, known as a "question mark ear," micrognathia and mandibular condyle hypoplasia. Recently, phospholipase C, β 4 (PLCB4) mutations were identified as the major cause of autosomal dominant ACS, with mutations of the PLCB4 catalytic domain predicted to have a dominant negative effect. In addition, one ACS patient born to related parents harbored a homozygous partial deletion of PLCB4, and presented with ACS plus central apnea and macropenis; these features had not been previously reported in association with ACS. His parents, each with a heterozygous partial PLCB4 deletion, were phenotypically normal, suggesting autosomal recessive inheritance of ACS, with complete loss of function of PLCB4 predicted in the patient. We herein describe two brothers with ACS caused by compound heterozygous splice site mutations in PLCB4. The patients were born to the same unrelated and healthy parents, with each parent harboring one of the mutations, indicating autosomal recessive ACS. Both patients reported here had mixed apneas, gastrointestinal transit defects and macropenis, in addition to typical craniofacial features of ACS. This is the first example of ACS caused by compound heterozygous splice site mutations in PLCB4, the second autosomal recessive case of ACS confirmed by molecular analysis, and strengthens the link between complete loss of function of PLCB4 and extra-craniofacial features. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2013 · American Journal of Medical Genetics Part A
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    • "Obstructive Sleep Apnea (OSA) is a prevalent disorder with significant neurocognitive and cardiovascular consequences (Lavie et al., 2000; Pepperd et al., 2000; Roth et al., 1995). Sleep related changes in the activity of pharyngeal muscles are considered to be a major factor causing obstructions (Eckert et al., 2009; White, 2005). As a consequence there has been considerable interest in the motor control of these muscles, particularly of genioglossus (GG) and tensor palatini (TP), largely because they are relatively accessible in humans and because they are considered representative of inspiratory phasic and tonic muscles respectively (Tangel et al., 1992). "
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    ABSTRACT: Common oscillatory inputs to genioglossus (GG) and tensor palatini (TP) motoneurons were assessed using coherence analysis. Oscillations in the ranges 0 to 5Hz (common drive) and 10 to 30Hz (short term synchrony) were analyzed. GG and TP electromyograms were recorded via intramuscular fine wire electrodes in 32 subjects during wakefulness. Coherence analysis was conducted on 201 pairs of motor units paired according to their discharge patterns. Results were similar for the two muscles. Common drive was significantly higher for unilateral than bilateral pairs of units (p<.001), and was highest in Inspiratory Tonic pairs and lowest in Tonic pairs (p<.001). Pairs constructed from one muscle had higher common drive than pairs from two muscles (p<.001), the difference being greater for tonic pairs (interaction effect, p=.003). Short term synchrony was weak. The results indicate strong common drive to GG and TP phasic motoneurons, while common drive to Tonic motoneurons was weaker and idiosyncratic to each muscle.
    Full-text · Article · Jun 2013 · Respiratory Physiology & Neurobiology
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    • "Taken together, RV distension, impairment of LV filling, and increased sympathetic activity will occur, and can synergistically increase myocardial oxygen demand in a contextual setting in which apnea-related hypoxia will reduce tissue oxygen delivery (Kasai and Bradley, 2011). Upon arousal from sleep, sympathetic activity, blood pressure, cardiac output, and heart rate rapidly increase, resulting in more increased cardiac oxygen demand at a time when arterial oxygen saturation is at its lowest level (Eckert et al., 2009). This can precipitate more severe myocardial ischemia and impair cardiac contractility and diastolic relaxation. "
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    ABSTRACT: Sleep is involved in the regulation of major organ functions in the human body, and disruption of sleep potentially can elicit organ dysfunction. Obstructive sleep apnea (OSA) is the most prevalent sleep disorder of breathing in adults and children, and its manifestations reflect the interactions between intermittent hypoxia, intermittent hypercapnia, increased intra-thoracic pressure swings, and sleep fragmentation, as elicited by the episodic changes in upper airway resistance during sleep. The sympathetic nervous system is an important modulator of the cardiovascular, immune, endocrine and metabolic systems, and alterations in autonomic activity may lead to metabolic imbalance and organ dysfunction. Here we review how OSA and its constitutive components can lead to perturbation of the autonomic nervous system in general, and to altered regulation of catecholamines, both of which then playing an important role in some of the mechanisms underlying OSA-induced morbidities.
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