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David P White - One of the best experts on this subject based on the ideXlab platform.
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desipramine improves Upper Airway collapsibility and reduces osa severity in patients with minimal Muscle compensation
European Respiratory Journal, 2016Co-Authors: Luigi Tarantomontemurro, Danny J Eckert, Scott A. Sands, Bradley A. Edwards, Ali Azarbarzin, Melania Marques, Camila Maria De Melo, David P WhiteAbstract:We recently demonstrated that desipramine reduces the sleep-related loss of Upper Airway dilator Muscle activity and reduces pharyngeal collapsibility in healthy humans without obstructive sleep apnoea (OSA). The aim of the present physiological study was to determine the effects of desipramine on Upper Airway collapsibility and apnoea-hypopnea index (AHI) in OSA patients.A placebo-controlled, double-blind, randomised crossover trial in 14 OSA patients was performed. Participants received treatment or placebo in randomised order before sleep. Pharyngeal collapsibility (critical collapsing pressure of the Upper Airway (Pcrit)) and ventilation under both passive (V'0,passive) and active (V'0,active) Upper Airway Muscle conditions were evaluated with continuous positive Airway pressure (CPAP) manipulation. AHI was quantified off CPAP.Desipramine reduced active Pcrit (median (interquartile range) -5.2 (4.3) cmH2O on desipramine versus -1.9 (2.7) cmH2O on placebo; p=0.049) but not passive Pcrit (-2.2 (3.4) versus -0.7 (2.1) cmH2O; p=0.135). A greater reduction in AHI occurred in those with minimal Muscle compensation (defined as V'0,active-V'0,passive) on placebo (r=0.71, p=0.009). The reduction in AHI was driven by the improvement in Muscle compensation (r=0.72, p=0.009).In OSA patients, noradrenergic stimulation with desipramine improves pharyngeal collapsibility and may be an effective treatment in patients with minimal Upper Airway Muscle compensation.
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Upper Airway collapsibility pcrit and pharyngeal dilator Muscle activity are sleep stage dependent
Sleep, 2016Co-Authors: Jayne C Carberry, Amy S Jordan, David P White, Andrew Wellman, Danny J EckertAbstract:STUDY OBJECTIVES An anatomically narrow/highly collapsible Upper Airway is the main cause of obstructive sleep apnea (OSA). Upper Airway Muscle activity contributes to Airway patency and, like apnea severity, can be sleep stage dependent. Conversely, existing data derived from a small number of participants suggest that Upper Airway collapsibility, measured by the passive pharyngeal critical closing pressure (Pcrit) technique, is not sleep stage dependent. This study aimed to determine the effect of sleep stage on Pcrit and Upper Airway Muscle activity in a larger cohort than previously tested. METHODS Pcrit and/or Muscle data were obtained from 72 adults aged 20-64 y with and without OSA.Pcrit was determined via transient reductions in continuous positive Airway pressure (CPAP) during N2, slow wave sleep (SWS) and rapid eye movement (REM) sleep. Genioglossus and tensor palatini Muscle activities were measured: (1) awake with and without CPAP, (2) during stable sleep on CPAP, and (3) in response to the CPAP reductions used to quantify Pcrit. RESULTS Pcrit was 4.9 ± 1.4 cmH2O higher (more collapsible) during REM versus SWS (P = 0.012), 2.3 ± 0.6 cmH2O higher during REM versus N2 (P < 0.001), and 1.6 ± 0.7 cmH2O higher in N2 versus SWS (P = 0.048). Muscle activity decreased from wakefulness to sleep and from SWS to N2 to REM sleep for genioglossus but not for tensor palatini. Pharyngeal Muscle activity increased by ∼50% by breath 5 following CPAP reductions. CONCLUSIONS Upper Airway collapsibility measured via the Pcrit technique and genioglossus Muscle activity vary with sleep stage. These findings should be taken into account when performing and interpreting "passive" Pcrit measurements.
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Enhanced Upper-Airway Muscle responsiveness is a distinct feature of overweight/obese individuals without sleep apnea.
American journal of respiratory and critical care medicine, 2014Co-Authors: Scott A. Sands, Amy S Jordan, Danny J Eckert, Atul Malhotra, Bradley A. Edwards, Robert L. Owens, James P. Butler, Richard J. Schwab, Stephen H. Loring, David P WhiteAbstract:Rationale: Body habitus is a major determinant of obstructive sleep apnea (OSA). However, many individuals do not have OSA despite being overweight/obese (body mass index > 25 kg/m2) for reasons that are not fully elucidated.Objectives: To determine the key physiologic traits (Upper-Airway anatomy/collapsibility, Upper-Airway Muscle responsiveness, chemoreflex control of ventilation, arousability from sleep) responsible for the absence of OSA in overweight/obese individuals.Methods: We compared key physiologic traits in 18 overweight/obese subjects without apnea (apnea–hypopnea index < 15 events per hour) with 25 overweight/obese matched patients with OSA (apnea–hypopnea index ≥ 15 events per hour) and 11 normal-weight nonapneic control subjects. Traits were measured by repeatedly lowering continuous positive Airway pressure to subtherapeutic levels for 3 minutes during non-REM sleep.Measurements and Main Results: Overweight/obese subjects without apnea exhibited a less collapsible Airway than overweight/...
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enhanced Upper Airway Muscle responsiveness is a distinct feature of overweight obese individuals without sleep apnea
American Journal of Respiratory and Critical Care Medicine, 2014Co-Authors: Scott A. Sands, Amy S Jordan, Danny J Eckert, Atul Malhotra, Bradley A. Edwards, Robert L. Owens, James P. Butler, Stephen H. Loring, Richard Schwab, David P WhiteAbstract:Rationale: Body habitus is a major determinant of obstructive sleep apnea (OSA). However, many individuals do not have OSA despite being overweight/obese (body mass index > 25 kg/m2) for reasons that are not fully elucidated.Objectives: To determine the key physiologic traits (Upper-Airway anatomy/collapsibility, Upper-Airway Muscle responsiveness, chemoreflex control of ventilation, arousability from sleep) responsible for the absence of OSA in overweight/obese individuals.Methods: We compared key physiologic traits in 18 overweight/obese subjects without apnea (apnea–hypopnea index < 15 events per hour) with 25 overweight/obese matched patients with OSA (apnea–hypopnea index ≥ 15 events per hour) and 11 normal-weight nonapneic control subjects. Traits were measured by repeatedly lowering continuous positive Airway pressure to subtherapeutic levels for 3 minutes during non-REM sleep.Measurements and Main Results: Overweight/obese subjects without apnea exhibited a less collapsible Airway than overweight/...
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differential effects of isoflurane and propofol on Upper Airway dilator Muscle activity and breathing
Anesthesiology, 2008Co-Authors: Matthias Eikermann, Amy S Jordan, David P White, S Zaremba, Atul Malhotra, Philipp Fassbender, Shiva Gautam, Nancy L ChamberlinAbstract:Upper Airway patency depends on an appropriate balance between the dilating force of pharyngeal Muscles and the collapsing force of negative intraluminal pressure, which is generated by respiratory “pump” Muscles. The genioglossus protects pharyngeal patency in humans. This Muscle receives various types of neural drive, including a phasic (in phase with inspiration) and tonic (expiratory) drive, distributed differentially across the hypoglossal motoneuron pool.1 In addition, reflex genioglossus activation in response to negative pharyngeal pressure stabilizes Upper Airway patency both in humans2 and in rats.3 General anesthetic agents,4–9 including propofol7,9 and isoflurane,8 can predispose the Upper Airway to collapse, partly by decreasing Upper Airway Muscle activity.4–7 In contrast, recent data suggest that anesthetics can increase genioglossus phasic activity,10,11 an apparent paradox. It is not clear which of these disparate observations—activation versus inhibition of Upper Airway dilator function—are anesthetic type/agent dependent or dependent on the study conditions used.4,10,11 Understanding the mechanism by which anesthetics activate or inhibit Upper Airway dilator Muscle activity is fundamental to their safe use in settings where Upper Airway patency is at risk, e.g., during conscious sedation. In theory, anesthetics could affect Upper Airway dilator activity by several mechanisms, including the following. First, in humans, anesthetics induce a dose-dependent decrease in hypercapnic and hypoxic ventilatory drive.12–14 Because the activity of hypoglossal motoneurons is in part respiratory related,4 a decrease in ventilatory drive could result in a suppression of hypoglossal motor activity.4 Second, anesthetics depress hypoglossal motoneurons,15,16 both directly and possibly indirectly by enhancing the activity of the inhibitory neurotransmitters γ-aminobutyric acid and glycine,17 receptor mechanisms that are tonically active at the hypoglossal motor nucleus.18 Third, animal studies have revealed barbiturates and volatile anesthetics can decrease skeletal Muscle contractility directly by a variety of cellular mechanisms.19,20 Fourth, anesthetics decrease arterial blood pressure,21 a condition that has been shown to activate phasic genioglossus activity.22 Fifth, the vagus nerve is important for mediating the interplay between lung volume and Upper Airway Muscle activity,23,24 and isoflurane may have vagolytic effects.25,26 Finally, it has recently been suggested that volatile anesthetics can increase phasic hypoglossal nerve discharge by altering neuronal activity in the Kolliker-Fuse region, which contains hypoglossal premotor motoneurons.10 Based on the observations of Roda et al.,10 we tested the a priori hypothesis that phasic genioglossus Muscle activity is higher during isoflurane anesthesia compared with propofol. We tested the secondary hypothesis that flow rate, a measure of respiratory drive, predicts the effects of anesthetics on phasic genioglossus activation. Third, with an exploratory intention, we sorted out the above mentioned variables which could mediate the effects of isoflurane at the genioglossus4,10,21,22,25–28 by controlling in subsets of experiments for carbon dioxide concentration, mean arterial blood pressure, Kolliker-Fuse neuron influence, or vagus nerve effects.
Aidan Bradford - One of the best experts on this subject based on the ideXlab platform.
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Oxidative Stress Impairs Upper Airway Muscle Endurance in an Animal Model of Sleep-Disordered Breathing
Advances in experimental medicine and biology, 2008Co-Authors: Mark Dunleavy, Aidan Bradford, Ken D. O'halloranAbstract:Obstructive sleep apnoea is characterised by intermittent hypoxia due to recurrent obstructions of the pharyngeal Airway during sleep. We have shown that chronic intermittent hypoxia impairs respiratory Muscle function and CNS control of Upper Airway patency. In this study, we tested the hypothesis that disruption of an endogenous antioxidant defence system exacerbates the effects of intermittent hypoxia on Upper Airway Muscle contractile function. Thirty-two male Wistar rats were placed in restrainers with their heads in hoods in which the ambient oxygen concentration could be modified by controlling the gas supply to the hoods. Sixteen rats were exposed to alternating equal periods of hypoxia and normoxia, twice per minute, 8 hours per day for 1 week. The remaining 16 animals were exposed to normoxia continuously under identical experimental conditions. In both groups, half the animals received daily injections of buthionine sulfoxamine (BSO), an inhibitor of the rate-limiting enzyme in glutathione synthesis. The other half received daily vehicle injections. At the end of the 1-week treatment period, the sternohyoid Muscles were removed and fatigue characteristics were determined in vitro. Intermittent hypoxia was associated with a decrease in sternohyoid Muscle endurance, an effect that was exacerbated by treatment with BSO. In separate experiments, daily treatment with the antioxidant N-acetyl cysteine blocked the deleterious effects of intermittent hypoxia on respiratory Muscle function. We suggest that oxidative stress contributes to impaired Upper Airway Muscle endurance in our animal model and that endogenous glutathione may be especially important in limiting free radical-induced Muscle dysfunction. Our results may have particular relevance to respiratory disorders associated with recurrent hypoxia, such as the sleep apnoea/hypopnoea syndrome.
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Does episodic hypoxia affect Upper Airway dilator Muscle function? Implications for the pathophysiology of obstructive sleep apnoea.
Respiratory physiology & neurobiology, 2005Co-Authors: Aidan Bradford, Michelle Mcguire, Ken D. O'halloranAbstract:Obstructive sleep apnoea (OSA) is characterised by repetitive collapse of the Upper Airway during sleep owing to a sleep-related decrement in Upper Airway Muscle activity with consequent failure of the pharyngeal dilator Muscles to oppose the collapsing pressure that is generated by the diaphragm and accessory Muscles during inspiration. The causes of Upper Airway obstruction during sleep are multi-factorial but there is evidence implicating intrinsic Upper Airway Muscle function and impaired central regulation of the Upper Airway Muscles in the pathophysiology of OSA. The condition is associated with episodic hypoxia due to recurrent apnoea. However, despite its obvious importance very little is known about the effects of episodic hypoxia on Upper Airway Muscle function. In this review, we examine the evidence that chronic intermittent hypoxia can affect Upper Airway Muscle structure and function and impair CNS control of the pharyngeal dilator Muscles. We review the literature and discuss results from our laboratory showing that episodic hypoxia/asphyxia reduces Upper Airway Muscle endurance and selectively impairs pharyngeal dilator EMG responses to physiological stimulation. Our observations lead us to speculate that episodic hypoxia--a consequence of periodic Airway occlusion--is responsible for progression of OSA through impairment of the neural control systems that regulate Upper Airway patency and through altered respiratory Muscle contractile function, leading to the establishment of a vicious cycle of further Airway obstruction and hypoxic insult that chronically exacerbates and perpetuates the condition. We conclude that chronic intermittent hypoxia/asphyxia contributes to the pathophysiology of sleep-disordered breathing.
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Effects of chronic intermittent asphyxia on haematocrit, pulmonary arterial pressure and skeletal Muscle structure in rats
Experimental physiology, 2003Co-Authors: Aidan BradfordAbstract:Sleep-disordered breathing in humans is a common condition associated with serious cardiovascular and other abnormalities. The prevalence and pathogenesis of increased haematocrit and pulmonary hypertension is controversial and it has been suggested that these changes only occur in patients who also have daytime continuous hypoxaemia. The hypothesis tested here is that the chronic intermittent hypoxia and asphyxia associated with sleep-disordered breathing causes erythropoiesis and pulmonary hypertension and that this occurs in the absence of periods of continuous hypoxia. In humans and animals with obstructive sleep apnoea, there are abnormalities of Upper Airway Muscle structure that have been ascribed to increased load placed on these Muscles. An alternative hypothesis is that chronic intermittent hypoxia and asphyxia cause changes in Upper Airway Muscle structure and function. To test these hypotheses, rats were exposed to intermittent hypoxia and asphyxia for 8 h per day for 5 weeks. This caused an increase in haematocrit, right ventricular weight and pulmonary arterial pressure. There were only slight changes in diaphragm, Upper Airway and limb Muscle structure and force production but in general, Muscle fatigability was increased. In conclusion chronic intermittent hypoxia and asphyxia cause an increase in haematocrit and pulmonary arterial pressure in the absence of periods of continuous hypoxia. Chronic intermittent hypoxia and asphyxia have little effect on skeletal Muscle structure and force production but increase Muscle fatigue. Increased Upper Airway Muscle fatigue could lead to a vicious cycle of further compromise in Upper Airway patency and further hypoxia and asphyxia.
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the effects of chronic episodic hypercapnic hypoxia on rat Upper Airway Muscle contractile properties and fiber type distribution
Chest, 2002Co-Authors: Michelle Mcguire, Marry Macdermott, Aidan BradfordAbstract:Objective: Obstructive sleep apnea (OSA) is caused by episodes of Upper Airway (UA) obstruction due to an inability of UA Muscles such as the geniohyoids and sternohyoids to maintain Airway patency. This results in chronic episodic hypercapnic hypoxia. Chronic continuous hypoxia and episodic hypocapnic hypoxia affect skeletal Muscle structure and function, but the effects of chronic episodic hypercapnic hypoxia on UA Muscle structure and function are unknown. Design: Rats breathed air and hypercapnic hypoxic gas twice per minute for 8 h/d for 5 weeks in order to mimic the intermittent hypercapnic hypoxia of OSA in humans. Isometric contractile properties were determined using strips of isolated geniohyoid and sternohyoid Muscles in physiologic saline solution at 30°C. Fiber-type distribution was determined by adenosine triphosphatase staining. Results: For both Muscles, chronic episodic hypercapnic hypoxia had no significant effect on twitch or tetanic tension, twitch/tetanic tension ratio, and tension-frequency relationship. There was a significant (p < 0.05) increase in geniohyoid fatigue (50.5 6.6% vs 43.6 5.8% of initial tension), but sternohyoid fatigue was reduced (31.5 5.2% vs 37.8 6.0% of initial tension). Geniohyoid type 1 fibers were reduced and type 2B fibers increased, whereas sternohyoid Muscle had an increase in type 1 and 2A fibers and a decrease in type 2B fibers. Conclusions: Chronic episodic hypercapnic hypoxia alters UA Muscle structure and function, changes that may affect the regulation of UA patency. (CHEST 2002; 122:1400 –1406)
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effects of chronic episodic hypoxia on rat Upper Airway Muscle contractile properties and fiber type distribution
Chest, 2002Co-Authors: Michelle Mcguire, M Macdermott, Aidan BradfordAbstract:Objective Contraction of Upper Airway (UA) Muscles such as the geniohyoids and sternohyoids dilates and/or stabilizes the UA, thereby maintaining its patency. Obstructive sleep apnea (OSA) is caused by episodes of UA collapse, and this results in chronic episodic hypoxia. Chronic continuous hypoxia affects skeletal Muscle structure and function, but the effects of chronic episodic hypoxia on UA Muscle structure and function are unknown. Design Rats were exposed to alternating periods of hypoxia and normoxia twice per minute for 8 h/d for 5 weeks in order to mimic the intermittent hypoxia of OSA in humans. Isometric contractile properties were determined using strips of isolated geniohyoid and sternohyoid Muscles in physiologic saline solution at 30°C. Fiber-type distribution was determined using adenosine triphosphatase staining. Results Chronic episodic hypoxia had no significant effect on twitch or tetanic tension, twitch/tetanic tension ratio, contractile kinetics, tension-frequency relationship, or fiber-type distribution for either the sternohyoid or geniohyoid Muscle. However, chronic episodic hypoxia did significantly increase sternohyoid and geniohyoid fatigue and reduced recovery from fatigue. Conclusions Chronic episodic hypoxia increases UA Muscle fatigue, an effect that may compromise the maintenance of UA patency.
John Trinder - One of the best experts on this subject based on the ideXlab platform.
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mechanisms of the deep slow wave sleep related increase of Upper Airway Muscle tone in healthy humans
Journal of Applied Physiology, 2017Co-Authors: Amelia J Hicks, Amy S Jordan, Atul Malhotra, Jennifer M Cori, Christian L Nicholas, Leszek Kubin, John G Semmler, David G Mcsharry, John TrinderAbstract:The characteristic increase in the activity of the Upper Airway dilator Muscle genioglossus during slow-wave sleep (SWS) in young healthy individuals was found to be related to increased stimulatio...
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Common drive to the Upper Airway Muscle genioglossus during inspiratory loading.
Journal of neurophysiology, 2015Co-Authors: Michael J Woods, Amy S Jordan, Christian L Nicholas, John G Semmler, Julia K. M. Chan, John TrinderAbstract:Common drive is thought to constitute a central mechanism by which the efficiency of a motor neuron pool is increased. This study tested the hypothesis that common drive to the Upper Airway Muscle ...
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The effect of sleep onset on Upper Airway Muscle activity in patients with sleep apnoea versus controls
The Journal of Physiology, 2005Co-Authors: Robert B. Fogel, David P White, Atul Malhotra, John Trinder, Darci Kleverlaan, Jill Raneri, Karen Schory, Robert J. PierceAbstract:Pharyngeal dilator Muscles are important in the pathophysiology of obstructive sleep apnoea syndrome (OSA). We have previously shown that during wakefulness, the activity of both the genioglossus (GGEMG) and tensor palatini (TPEMG) is greater in patients with OSA compared with controls. Further, EMG activity decreases at sleep onset, and the decrement is greater in apnoea patients than in healthy controls. In addition, it is known that the prevalence of OSA is greater in middle-aged compared with younger men. Thus, we had two goals in this study. First we compared Upper Airway Muscle activity between young and middle-aged healthy men compared with men with OSA. We also explored the mechanisms responsible for the decrement in Muscle activity at sleep onset in these groups. We investigated Muscle activity, ventilation , and Upper Airway resistance (UAR) during wakefulness and sleep onset (transition from α to θ EEG activity) in all three groups. Measurements were obtained during basal breathing (BB) and nasal continuous positive Airway pressure (CPAP) was applied to reduce negative pressure-mediated Muscle activation). We found that during wakefulness there was a gradation of GGEMG and UAR (younger < older < OSA) and that Muscle activity was reduced by the application of nasal CPAP (to a greater degree in the OSA patients). Although CPAP eliminated differences in UAR during wakefulness and sleep, GGEMG remained greater in the OSA patients. During sleep onset, a greater initial fall in GGEMG was seen in the OSA patients followed by subsequent Muscle recruitment in the third to fifth breaths following the α to θ transition. On the CPAP night, and GGEMG still fell further in the OSA patients compared with control subjects. CPAP prevented the rise in UAR at sleep onset along with the associated recruitment in GGEMG. Differences in TPEMG among the groups were not significant. These data suggest that the middle-aged men had Upper Airway function midway between that of young normal men and the abnormal Airway of those with OSA. Furthermore it suggests that the initial sleep onset reduction in Upper Airway Muscle activity is due to loss of a ‘wakefulness’ stimulus, rather than to loss of responsiveness to negative pressure, and that this wakefulness stimulus may be greater in the OSA patient than in healthy controls.
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Control of Upper Airway Muscle activity in younger versus older men during sleep onset.
The Journal of physiology, 2003Co-Authors: Robert B. Fogel, David P White, Atul Malhotra, Robert J. Pierce, Jill K. Edwards, Judy Dunai, Darci Kleverlaan, John TrinderAbstract:Pharyngeal dilator Muscles are clearly important in the pathophysiology of obstructive sleep apnoea syndrome (OSA). We have previously shown that the activity of both the genioglossus (GGEMG) and tensor palatini (TPEMG) are decreased at sleep onset, and that this decrement in Muscle activity is greater in the apnoea patient than in healthy controls. We have also previously shown this decrement to be greater in older men when compared with younger ones. In order to explore the mechanisms responsible for this decrement in Muscle activity nasal continuous positive Airway pressure (CPAP) was applied to reduce negative pressure mediated Muscle activation. We then investigated the effect of sleep onset (transition from predominantly alpha to predominantly theta EEG activity) on ventilation, Upper Airway Muscle activation and Upper Airway resistance (UAR) in middle-aged and younger healthy men. We found that both GGEMG and TPEMG were reduced by the application of nasal CPAP during wakefulness, but that CPAP did not alter the decrement in activity in either Muscle seen in the first two breaths following an alpha to theta transition. However, CPAP prevented both the rise in UAR at sleep onset that occurred on the control night, and the recruitment in GGEMG seen in the third to fifth breaths following the alpha to theta transition. Further, GGEMG was higher in the middle-aged men than in the younger men during wakefulness and was decreased more in the middle-aged men with the application of nasal CPAP. No differences were seen in TPEMG between the two age groups. These data suggest that the initial sleep onset reduction in Upper Airway Muscle activity is due to loss of a 'wakefulness' stimulus, rather than to loss of responsiveness to negative pressure. In addition, it suggests that in older men, higher wakeful Muscle activity is due to an anatomically more collapsible Upper Airway with more negative pressure driven Muscle activation. Sleep onset per se does not appear to have a greater effect on Upper Airway Muscle activity as one ages.
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Control of Upper Airway Muscle activity in younger versus older men during sleep onset
The Journal of Physiology, 2003Co-Authors: Robert B. Fogel, David P White, Atul Malhotra, Robert J. Pierce, Jill K. Edwards, Judy Dunai, Darci Kleverlaan, John TrinderAbstract:Pharyngeal dilator Muscles are clearly important in the pathophysiology of obstructive sleep apnoea syndrome (OSA). We have previously shown that the activity of both the genioglossus (GGEMG) and tensor palatini (TPEMG) are decreased at sleep onset, and that this decrement in Muscle activity is greater in the apnoea patient than in healthy controls. We have also previously shown this decrement to be greater in older men when compared with younger ones. In order to explore the mechanisms responsible for this decrement in Muscle activity nasal continuous positive Airway pressure (CPAP) was applied to reduce negative pressure mediated Muscle activation. We then investigated the effect of sleep onset (transition from predominantly α to predominantly θ EEG activity) on ventilation, Upper Airway Muscle activation and Upper Airway resistance (UAR) in middle-aged and younger healthy men. We found that both GGEMG and TPEMG were reduced by the application of nasal CPAP during wakefulness, but that CPAP did not alter the decrement in activity in either Muscle seen in the first two breaths following an α to θ transition. However, CPAP prevented both the rise in UAR at sleep onset that occurred on the control night, and the recruitment in GGEMG seen in the third to fifth breaths following the α to θ transition. Further, GGEMG was higher in the middle-aged men than in the younger men during wakefulness and was decreased more in the middle-aged men with the application of nasal CPAP. No differences were seen in TPEMG between the two age groups. These data suggest that the initial sleep onset reduction in Upper Airway Muscle activity is due to loss of a ‘wakefulness’ stimulus, rather than to loss of responsiveness to negative pressure. In addition, it suggests that in older men, higher wakeful Muscle activity is due to an anatomically more collapsible Upper Airway with more negative pressure driven Muscle activation. Sleep onset per se does not appear to have a greater effect on Upper Airway Muscle activity as one ages.
Atul Malhotra - One of the best experts on this subject based on the ideXlab platform.
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catecholaminergic a1 c1 neurons contribute to the maintenance of Upper Airway Muscle tone but may not participate in nrem sleep related depression of these Muscles
Respiratory Physiology & Neurobiology, 2017Co-Authors: Irma Rukhadze, Atul Malhotra, Nancy J Carballo, Sathyajit S Bandaru, Patrick M Fuller, Victor B. FenikAbstract:Neural mechanisms of obstructive sleep apnea, a common sleep-related breathing disorder, are incompletely understood. Hypoglossal motoneurons, which provide tonic and inspiratory activation of genioglossus (GG) Muscle (a major Upper Airway dilator), receive catecholaminergic input from medullary A1/C1 neurons. We aimed to determine the contribution of A1/C1 neurons in control of GG Muscle during sleep and wakefulness. To do so, we placed injections of a viral vector into DBH-cre mice to selectively express the hMD4i inhibitory chemoreceptors in A1/C1 neurons. Administration of the hM4Di ligand, clozapine-N-oxide (CNO), in these mice decreased GG Muscle activity during NREM sleep (F1,1,3=17.1, p<0.05); a similar non-significant decrease was observed during wakefulness. CNO administration had no effect on neck Muscle activity, respiratory parameters or state durations. In addition, CNO-induced inhibition of A1/C1 neurons did not alter the magnitude of the naturally occurring depression of GG activity during transitions from wakefulness to NREM sleep. These findings suggest that A1/C1 neurons have a net excitatory effect on GG activity that is most likely mediated by hypoglossal motoneurons. However, the activity of A1/C1 neurons does not appear to contribute to NREM sleep-related inhibition of GG Muscle activity, suggesting that A1/C1 neurons regulate Upper Airway patency in a state-independent manner.
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mechanisms of the deep slow wave sleep related increase of Upper Airway Muscle tone in healthy humans
Journal of Applied Physiology, 2017Co-Authors: Amelia J Hicks, Amy S Jordan, Atul Malhotra, Jennifer M Cori, Christian L Nicholas, Leszek Kubin, John G Semmler, David G Mcsharry, John TrinderAbstract:The characteristic increase in the activity of the Upper Airway dilator Muscle genioglossus during slow-wave sleep (SWS) in young healthy individuals was found to be related to increased stimulatio...
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Enhanced Upper-Airway Muscle responsiveness is a distinct feature of overweight/obese individuals without sleep apnea.
American journal of respiratory and critical care medicine, 2014Co-Authors: Scott A. Sands, Amy S Jordan, Danny J Eckert, Atul Malhotra, Bradley A. Edwards, Robert L. Owens, James P. Butler, Richard J. Schwab, Stephen H. Loring, David P WhiteAbstract:Rationale: Body habitus is a major determinant of obstructive sleep apnea (OSA). However, many individuals do not have OSA despite being overweight/obese (body mass index > 25 kg/m2) for reasons that are not fully elucidated.Objectives: To determine the key physiologic traits (Upper-Airway anatomy/collapsibility, Upper-Airway Muscle responsiveness, chemoreflex control of ventilation, arousability from sleep) responsible for the absence of OSA in overweight/obese individuals.Methods: We compared key physiologic traits in 18 overweight/obese subjects without apnea (apnea–hypopnea index < 15 events per hour) with 25 overweight/obese matched patients with OSA (apnea–hypopnea index ≥ 15 events per hour) and 11 normal-weight nonapneic control subjects. Traits were measured by repeatedly lowering continuous positive Airway pressure to subtherapeutic levels for 3 minutes during non-REM sleep.Measurements and Main Results: Overweight/obese subjects without apnea exhibited a less collapsible Airway than overweight/...
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enhanced Upper Airway Muscle responsiveness is a distinct feature of overweight obese individuals without sleep apnea
American Journal of Respiratory and Critical Care Medicine, 2014Co-Authors: Scott A. Sands, Amy S Jordan, Danny J Eckert, Atul Malhotra, Bradley A. Edwards, Robert L. Owens, James P. Butler, Stephen H. Loring, Richard Schwab, David P WhiteAbstract:Rationale: Body habitus is a major determinant of obstructive sleep apnea (OSA). However, many individuals do not have OSA despite being overweight/obese (body mass index > 25 kg/m2) for reasons that are not fully elucidated.Objectives: To determine the key physiologic traits (Upper-Airway anatomy/collapsibility, Upper-Airway Muscle responsiveness, chemoreflex control of ventilation, arousability from sleep) responsible for the absence of OSA in overweight/obese individuals.Methods: We compared key physiologic traits in 18 overweight/obese subjects without apnea (apnea–hypopnea index < 15 events per hour) with 25 overweight/obese matched patients with OSA (apnea–hypopnea index ≥ 15 events per hour) and 11 normal-weight nonapneic control subjects. Traits were measured by repeatedly lowering continuous positive Airway pressure to subtherapeutic levels for 3 minutes during non-REM sleep.Measurements and Main Results: Overweight/obese subjects without apnea exhibited a less collapsible Airway than overweight/...
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neostigmine but not sugammadex impairs Upper Airway dilator Muscle activity and breathing
BJA: British Journal of Anaesthesia, 2008Co-Authors: Amy S Jordan, Matthias Eikermann, S Zaremba, Atul Malhotra, Carl E Rosow, Nancy L ChamberlinAbstract:Background Cholinesterase inhibitor-based reversal agents, given in the absence of neuromuscular block, evoke a partial Upper Airway obstruction by decreasing skeletal Upper Airway Muscle function. Sugammadex reverses neuromuscular block by encapsulating rocuronium. However, its effects on Upper Airway integrity and breathing are unknown.
Robert B. Fogel - One of the best experts on this subject based on the ideXlab platform.
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The effect of sleep onset on Upper Airway Muscle activity in patients with sleep apnoea versus controls
The Journal of Physiology, 2005Co-Authors: Robert B. Fogel, David P White, Atul Malhotra, John Trinder, Darci Kleverlaan, Jill Raneri, Karen Schory, Robert J. PierceAbstract:Pharyngeal dilator Muscles are important in the pathophysiology of obstructive sleep apnoea syndrome (OSA). We have previously shown that during wakefulness, the activity of both the genioglossus (GGEMG) and tensor palatini (TPEMG) is greater in patients with OSA compared with controls. Further, EMG activity decreases at sleep onset, and the decrement is greater in apnoea patients than in healthy controls. In addition, it is known that the prevalence of OSA is greater in middle-aged compared with younger men. Thus, we had two goals in this study. First we compared Upper Airway Muscle activity between young and middle-aged healthy men compared with men with OSA. We also explored the mechanisms responsible for the decrement in Muscle activity at sleep onset in these groups. We investigated Muscle activity, ventilation , and Upper Airway resistance (UAR) during wakefulness and sleep onset (transition from α to θ EEG activity) in all three groups. Measurements were obtained during basal breathing (BB) and nasal continuous positive Airway pressure (CPAP) was applied to reduce negative pressure-mediated Muscle activation). We found that during wakefulness there was a gradation of GGEMG and UAR (younger < older < OSA) and that Muscle activity was reduced by the application of nasal CPAP (to a greater degree in the OSA patients). Although CPAP eliminated differences in UAR during wakefulness and sleep, GGEMG remained greater in the OSA patients. During sleep onset, a greater initial fall in GGEMG was seen in the OSA patients followed by subsequent Muscle recruitment in the third to fifth breaths following the α to θ transition. On the CPAP night, and GGEMG still fell further in the OSA patients compared with control subjects. CPAP prevented the rise in UAR at sleep onset along with the associated recruitment in GGEMG. Differences in TPEMG among the groups were not significant. These data suggest that the middle-aged men had Upper Airway function midway between that of young normal men and the abnormal Airway of those with OSA. Furthermore it suggests that the initial sleep onset reduction in Upper Airway Muscle activity is due to loss of a ‘wakefulness’ stimulus, rather than to loss of responsiveness to negative pressure, and that this wakefulness stimulus may be greater in the OSA patient than in healthy controls.
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Sleep · 2: Pathophysiology of obstructive sleep apnoea/hypopnoea syndrome
Thorax, 2004Co-Authors: Robert B. Fogel, Atul Malhotra, David P WhiteAbstract:The pathogenesis of Airway obstruction in patients with obstructive sleep apnoea/hypopnoea syndrome is reviewed. The primary defect is probably an anatomically small or collapsible pharyngeal Airway, in combination with a sleep induced fall in Upper Airway Muscle activity.
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Control of Upper Airway Muscle activity in younger versus older men during sleep onset.
The Journal of physiology, 2003Co-Authors: Robert B. Fogel, David P White, Atul Malhotra, Robert J. Pierce, Jill K. Edwards, Judy Dunai, Darci Kleverlaan, John TrinderAbstract:Pharyngeal dilator Muscles are clearly important in the pathophysiology of obstructive sleep apnoea syndrome (OSA). We have previously shown that the activity of both the genioglossus (GGEMG) and tensor palatini (TPEMG) are decreased at sleep onset, and that this decrement in Muscle activity is greater in the apnoea patient than in healthy controls. We have also previously shown this decrement to be greater in older men when compared with younger ones. In order to explore the mechanisms responsible for this decrement in Muscle activity nasal continuous positive Airway pressure (CPAP) was applied to reduce negative pressure mediated Muscle activation. We then investigated the effect of sleep onset (transition from predominantly alpha to predominantly theta EEG activity) on ventilation, Upper Airway Muscle activation and Upper Airway resistance (UAR) in middle-aged and younger healthy men. We found that both GGEMG and TPEMG were reduced by the application of nasal CPAP during wakefulness, but that CPAP did not alter the decrement in activity in either Muscle seen in the first two breaths following an alpha to theta transition. However, CPAP prevented both the rise in UAR at sleep onset that occurred on the control night, and the recruitment in GGEMG seen in the third to fifth breaths following the alpha to theta transition. Further, GGEMG was higher in the middle-aged men than in the younger men during wakefulness and was decreased more in the middle-aged men with the application of nasal CPAP. No differences were seen in TPEMG between the two age groups. These data suggest that the initial sleep onset reduction in Upper Airway Muscle activity is due to loss of a 'wakefulness' stimulus, rather than to loss of responsiveness to negative pressure. In addition, it suggests that in older men, higher wakeful Muscle activity is due to an anatomically more collapsible Upper Airway with more negative pressure driven Muscle activation. Sleep onset per se does not appear to have a greater effect on Upper Airway Muscle activity as one ages.
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Control of Upper Airway Muscle activity in younger versus older men during sleep onset
The Journal of Physiology, 2003Co-Authors: Robert B. Fogel, David P White, Atul Malhotra, Robert J. Pierce, Jill K. Edwards, Judy Dunai, Darci Kleverlaan, John TrinderAbstract:Pharyngeal dilator Muscles are clearly important in the pathophysiology of obstructive sleep apnoea syndrome (OSA). We have previously shown that the activity of both the genioglossus (GGEMG) and tensor palatini (TPEMG) are decreased at sleep onset, and that this decrement in Muscle activity is greater in the apnoea patient than in healthy controls. We have also previously shown this decrement to be greater in older men when compared with younger ones. In order to explore the mechanisms responsible for this decrement in Muscle activity nasal continuous positive Airway pressure (CPAP) was applied to reduce negative pressure mediated Muscle activation. We then investigated the effect of sleep onset (transition from predominantly α to predominantly θ EEG activity) on ventilation, Upper Airway Muscle activation and Upper Airway resistance (UAR) in middle-aged and younger healthy men. We found that both GGEMG and TPEMG were reduced by the application of nasal CPAP during wakefulness, but that CPAP did not alter the decrement in activity in either Muscle seen in the first two breaths following an α to θ transition. However, CPAP prevented both the rise in UAR at sleep onset that occurred on the control night, and the recruitment in GGEMG seen in the third to fifth breaths following the α to θ transition. Further, GGEMG was higher in the middle-aged men than in the younger men during wakefulness and was decreased more in the middle-aged men with the application of nasal CPAP. No differences were seen in TPEMG between the two age groups. These data suggest that the initial sleep onset reduction in Upper Airway Muscle activity is due to loss of a ‘wakefulness’ stimulus, rather than to loss of responsiveness to negative pressure. In addition, it suggests that in older men, higher wakeful Muscle activity is due to an anatomically more collapsible Upper Airway with more negative pressure driven Muscle activation. Sleep onset per se does not appear to have a greater effect on Upper Airway Muscle activity as one ages.
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Upper Airway Muscle responsiveness to rising PCO(2) during NREM sleep.
Journal of applied physiology (Bethesda Md. : 1985), 2000Co-Authors: Giora Pillar, Atul Malhotra, Robert B. Fogel, Josée Beauregard, David I. Slamowitz, Steven Shea, David P WhiteAbstract:Although pharyngeal Muscles respond robustly to increasing Pco 2 during wakefulness, the effect of hypercapnia on Upper Airway Muscle activation during sleep has not been carefully assessed. This m...
