Potential therapeutic targets in obstructive sleep apnoea

Saboisky, Julian P.; Chamberlin, Nancy L.; Malhotra, Atul

doi:10.1517/14728220903005608

Cited by 23 publications

(25 citation statements)

References 140 publications

(143 reference statements)

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“…Recent evidence suggests that the pathogenesis of sleep apnea involves a complex interplay of upper airway anatomy (121), pharyngeal dilator motor control (69, 132), ventilatory control instability (loop gain) (17, 50, 154, 160), alone and/or in combination. The contribution of each of these factors to OSA in a given individual is quite variable (115), emphasizing the importance of defining the underlying mechanism of OSA in afflicted patients to achieve the goal of individualized, targeted therapy (115). This article focuses on the mechanics of the upper airway, understanding that other factors are thoroughly discussed elsewhere in the Handbook and in the literature (40).…”

Section: Introductionmentioning

confidence: 99%

Mechanical Properties of the Upper Airway

Strohl

Butler

Malhotra

2012

Comprehensive Physiology

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108

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The importance of the upper airway (nose, pharynx, and larynx) in health and in the pathogenesis of sleep apnea, asthma, and other airway diseases, discussed elsewhere in the Comprehensive Physiology series, prompts this review of the biomechanical properties and functional aspects of the upper airway. There is a literature based on anatomic or structural descriptions in static circumstances, albeit studied in limited numbers of individuals in both health and disease. As for dynamic features, the literature is limited to studies of pressure and flow through all or parts of the upper airway and to the effects of muscle activation on such features; however, the links between structure and function through airway size, shape, and compliance remain a topic that is completely open for investigation, particularly through analyses using concepts of fluid and structural mechanics. Throughout are included both historically seminal references, as well as those serving as signposts or updated reviews. This article should be considered a resource for concepts needed for the application of biomechanical models of upper airway physiology, applicable to understanding the pathophysiology of disease and anticipated results of treatment interventions.

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Section: Introductionmentioning

confidence: 99%

Mechanical Properties of the Upper Airway

Strohl

Butler

Malhotra

2012

Comprehensive Physiology

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108

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“…While pharmacological agents that increase genioglossal muscle activity (such as ampakines) may be a viable strategy for OSA therapy (e.g., Refs. 28,41,53), the ideal therapeutic targets remain unclear.…”

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confidence: 99%

Recruitment and rate-coding strategies of the human genioglossus muscle

Saboisky

Jordan

Eckert

et al. 2010

Journal of Applied Physiology

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Saboisky JP, Jordan AS, Eckert DJ, White DP, Trinder JA, Nicholas CL, Gautam S, Malhotra A. Recruitment and rate-coding strategies of the human genioglossus muscle. J Appl Physiol 109: 1939-1949. First published October 14, 2010 doi:10.1152/japplphysiol.00812.2010.-Single motor unit (SMU) analysis provides a means to examine the motor control of a muscle. SMUs in the genioglossus show considerable complexity, with several different firing patterns. Two of the primary stimuli that contribute to genioglossal activation are carbon dioxide (CO 2) and negative pressure, which act through chemoreceptor and mechanoreceptor activation, respectively. We sought to determine how these stimuli affect the behavior of genioglossus SMUs. We quantified genioglossus SMU discharge activity during periods of quiet breathing, elevated CO2 (facilitation), and continuous positive airway pressure (CPAP) administration (inhibition). CPAP was applied in 2-cmH2O increments until 10 cmH2O during hypercapnia. Five hundred ninety-one periods (each ϳ3 breaths) of genioglossus SMU data were recorded using wire electrodes(n ϭ 96 units) from 15 awake, supine subjects. Overall hypercapnic stimulation increased the discharge rate of genioglossus units (20.9 Ϯ 1.0 vs. 22.7 Ϯ 0.9 Hz). Inspiratory units were activated ϳ13% earlier in the inspiratory cycle, and the units fired for a longer duration (80.6 Ϯ 5.1 vs. 105.3 Ϯ 4.2% inspiratory time; P Ͻ 0.05). Compared with baseline, an additional 32% of distinguishable SMUs within the selective electrode recording area were recruited with hypercapnia. CPAP led to progressive SMU inhibition; at ϳ6 cmH 2O, there were similar numbers of SMUs active compared with baseline, with peak frequencies of inspiratory units close to baseline, despite elevated CO 2 levels. At 10 cmH2O, the number of units was 36% less than baseline. Genioglossus inspiratory phasic SMUs respond to hypercapnic stimulation with changes in recruitment and rate coding. The SMUs respond to CPAP with derecruitment as a homogeneous population, and inspiratory phasic units show slower discharge rates. Understanding upper airway muscle recruitment/derecruitment may yield therapeutic targets for maintenance of pharyngeal patency.

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“…Similarly, abnormal ventilatory control (loop gain) may be important in only a subgroup of patients with OSA 2. As a result, the concept of individualised therapy has now emerged, such that treatment of the major underlying abnormality is likely to be beneficial in the appropriately targeted patient subgroups 3. In theory, patients with OSA who respond well to palatal surgery probably primarily have an abnormality in the velopharyngeal anatomy,4 whereas those who respond well to oxygen may have mainly an abnormality in ventilatory control instability 5 6…”

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confidence: 99%