Respiratory Muscle Activity Research Articles

Sleep, sleep disordered breathing, and nocturnal hypoventilation in children with neuromuscular diseases

Sleep disordered breathing (SDB) is now well recognized in children with neuromuscular diseases (NMD) and may lead to significant morbidity and increased mortality. Predisposing factors to SDB in children with NMD include reduced ventilatory responses, reduced activity of respiratory muscles during sleep and poor lung mechanics due to the underlying neuro-muscular disorder. SDB may present long before signs of respiratory failure emerge. When untreated, SDB may contribute to significant cardiovascular morbidities, neuro-cognitive deficits and premature death. One of the problems in detecting SDB in patients with NMD is the lack of correlation between lung function testing and daytime gas exchange. Polysomnography is the preferred method to evaluate for SDB in children with NMD. When the diagnosis of SDB is confirmed, treatment by non-invasive ventilation (NIV) is usually recommended. However, other modalities of mechanical ventilation do exist and may be indicated in combination with or without other supportive measures.

Telemetered activity of the respiratory muscles in the ferret: A relevant approach for monitoring the emetic reflex

Telemetered activity of the respiratory muscles in the ferret: A relevant approach for monitoring the emetic reflex

Long‐term facilitation of upper airway muscle activity induced by episodic upper airway negative pressure and hypoxia in spontaneously breathing anaesthetized rats

Obstruction of the upper airway (UA) is associated with episodes of hypoxia and upper airway negative pressure (UANP). In the companion paper it is shown that episodic hypoxia elicits long-term facilitation (LTF) of tongue protrudor, retractor and respiratory pump muscle activity. However, whether repeated exposure to UANP also induces LTF is unknown. We hypothesized that repetitive exposure to UANP would induce LTF of UA and respiratory pump muscle activity and when coupled with hypoxia, as occurs when the UA obstructs, would lead to an even greater facilitation of muscle activity and the response to UANP. Experiments were performed in 24 anaesthetized, spontaneously breathing rats with intact vagi. To induce LTF, UANP stimuli (-10 cmH(2)O) of 5 s duration were delivered every 30 s for 3 min (+/- hypoxia). This was repeated eight times over 1 h, each 3 min episode separated by 5 min of normoxia. Genioglossus (GG), hyoglossus (HG) and diaphragm (Dia) muscle activity was recorded before, during and for 1 h following the last exposure to episodic UANP alone (n = 8), UANP and hypoxia together (n = 8) or normoxia alone (n = 8). During the final hour, single pulses of UANP were applied at 1 min and every 10 min thereafter to determine whether LTF of the response to UANP had been induced. Our results show that LTF of GG muscle activity and its response to UANP was induced following exposure to episodic UANP stimuli alone and UANP applied during hypoxia. However, there was no significant difference between these responses. Episodic UANP alone also induced LTF of HG muscle activity but this effect did not manifest until 40 min following the last episode of repeated UANP stimulation. In the presence of hypoxia, no LTF of HG muscle response to UANP was found. In conclusion, episodic UANP stimulation induces LTF of UA dilator and retractor tongue muscles, but no further facilitation occurs when coupled with hypoxia. This response may serve as an important protective mechanism of respiratory homeostasis during sleep, particularly in patients who suffer from obstructive sleep apnoea.

Respiratory muscle activity and dyspnea during exercise in chronic obstructive pulmonary disease

We aimed to determine by non-invasive EMG, whether during exercise: (1) COPD patients increase scalene and intercostal EMG activity, (2) increased EMG activity is associated with increased dyspnea, and (3) the ratio between EMG activity and volume displacement is increased in COPD compared to healthy subjects (HS). During a maximal incremental cycle test, scalene and intercostal EMG was derived transcutaneously in 17 COPD patients and 10 HS. Dyspnea was quantified using a Borg scale, ranging from zero to 10 (maximal dyspnea). For analyses the ratio between inspiratory muscle activity during exercise and activity during quiet breathing was used (logEMGAR). In COPD patients, scalene and intercostal activity increased at greater rate early in exercise compared to that of the HS. With a doubling of the logEMGAR, in COPD, dyspnea increased with 2.8/3.8 points, while in the HS, dyspnea increased less with 1.1/1.4 points. In COPD, there was a larger increase in EMG activity relatively to tidal volume increases.

Role of the respiratory muscles in acute respiratory failure of COPD: lessons from weaning failure

It is problematic to withhold therapy in a patient with chronic obstructive pulmonary disease (COPD) who presents with acute respiratory failure so that detailed physiological measurements can be obtained. Accordingly, most information on respiratory muscle activity in patients experiencing acute respiratory failure has been acquired by studying patients who fail a trial of weaning after a period of mechanical ventilation. Such patients experience marked increases in inspiratory muscle load consequent to increases in resistance, elastance, and intrinsic positive end-expiratory pressure. Inspiratory muscle strength is reduced secondary to hyperinflation and possibly direct muscle damage and the release of inflammatory mediators. Most patients recruit both their sternomastoid and expiratory muscles, even though airflow limitation prevents the expiratory muscles from lowering lung volume. Even when acute hypercapnia is present, patients do not exhibit respiratory center depression; indeed, voluntary activation of the diaphragm, in absolute terms, is greater in hypercapnic patients than in normocapnic patients. Instead, the major mechanism of acute hypercapnia is the development of rapid shallow breathing. Despite the marked increase in mechanical load and decreased force-generating capacity of the inspiratory muscles, patients do not develop long-lasting muscle fatigue, at least over the period of a failed weaning trial. Although the disease originates within the lung parenchyma, much of the distress faced by patients with COPD, especially during acute respiratory failure, is caused by the burdens imposed on the respiratory muscles.

Respiratory muscle function and activation in chronic obstructive pulmonary disease

Inspiratory muscles are uniquely adapted for endurance, but their function is compromised in chronic obstructive pulmonary disease (COPD) due to increased loads, reduced mechanical advantage, and increased ventilatory requirements. The hyperinflation of COPD reduces the flow and pressure-generating capacity of the diaphragm. This is compensated by a threefold increase in neural drive, adaptations of the chest wall and diaphragm shape to accommodate the increased volume, and adaptations of muscle fibers to preserve strength and increase endurance. Paradoxical indrawing of the lower costal margin during inspiration in severe COPD (Hoover's sign) correlates with high inspiratory drive and severe airflow obstruction rather than contraction of radially oriented diaphragm fibers. The inspiratory muscles remain highly resistant to fatigue in patients with COPD, and the ultimate development of ventilatory failure is associated with insufficient central drive. Sleep is associated with reduced respiratory drive and impairments of lung and chest wall function, which are exaggerated in COPD patients. Profound hypoxemia and hypercapnia can occur in rapid eye movement sleep and contribute to the development of cor pulmonale. Inspiratory muscles adapt to chronic loading with an increased proportion of slow, fatigue-resistant fiber types, increased oxidative capacity, and reduced fiber cross-sectional area, but the capacity of the diaphragm to increase ventilation in exercise is compromised in COPD. In COPD, neural drive to the diaphragm increases to near maximal levels in exercise, but it does not develop peripheral muscle fatigue. The improvement in exercise capacity and dyspnea following lung volume reduction surgery is associated with a substantial reduction in neural drive to the inspiratory muscles.

Responses of thoracic spinal interneurons to vestibular stimulation in decerebrate cats

Stimulation of vestibular receptors produces changes in respiratory muscle activity as well as alterations in sympathetic outflow. Unlike vestibular reflexes acting on the limbs, vestibulo‐respiratory and ‐sympathetic responses are elicited by otolith organ inputs, particularly those generated by body rotations in the pitch plane. Recent studies have shown that thoracic interneurons make connections with respiratory motoneurons and sympathetic preganglionic neurons, but the responses of these cells to vestibular stimulation have not been explored. In the present study, recordings were made from thoracic interneurons in decerebrate, paralyzed cats. 60% of thoracic interneurons were activated by electrical stimulation of vestibular afferents at short latency. The majority of these cells exhibited response dynamics similar to those of otolith organs. 75% of the units were activated by tilts in the roll plane or the planes of the vertical semicircular canals; few cells responded best to pitch rotations. These data show that vestibular signals to thoracic interneurons are distinct from those transmitted to the cervical and lumbar spinal cord; however the spatial properties of the responses of the cells to body rotation differ from that of respiratory and sympathetic outflow. Presumably, the latter responses are synthesized through the integration of signals.

Application of histamine or serotonin to the hypoglossal nucleus increases genioglossus muscle activity across the wake–sleep cycle

The decrease in genioglossus (GG) muscle activity during sleep, especially rapid eye movement (REM) or paradoxical sleep, can lead to airway occlusion and obstructive sleep apnoea (OSA). The hypoglossal nucleus innervating the GG muscle is under the control of serotonergic, noradrenergic and histaminergic neurons that cease firing during paradoxical sleep. The objectives of this study were to determine the effect on GG muscle activity during different wake-sleep states of the microdialysis application of serotonin, histamine (HA) or noradrenaline (NE) to the hypoglossal nucleus in freely moving cats. Six adult cats were implanted with electroencephalogram, electro-oculogram and neck electromyogram electrodes to record wake-sleep states and with GG muscle and diaphragm electrodes to record respiratory muscle activity. Microdialysis probes were inserted into the hypoglossal nucleus for monoamine application. Changes in GG muscle activity were assessed by power spectrum analysis. In the baseline conditions, tonic GG muscle activity decreased progressively and significantly from wakefulness to slow-wave sleep and even further during slow-wave sleep with ponto-geniculo-occipital waves and paradoxical sleep. Application of serotonin or HA significantly increased GG muscle activity during the wake-sleep states when compared with controls. By contrast, NE had no excitatory effect. Our results indicate that both serotonin and HA have a potent excitatory action on GG muscle activity, suggesting multiple aminergic control of upper airway muscle activity during the wake-sleep cycle. These data might help in the development of pharmacological approaches for the treatment of OSA.

Implications of an avian‐style respiratory system for gigantism in sauropod dinosaurs

In light of evidence for avian-like lungs in saurischian dinosaurs, the physiological implications of cross-current gas exchange and voluminous, highly heterogeneous lungs for sauropod gigantism are critically examined. At 12 ton the predicted body temperature and metabolic rate of a growing sauropod would be similar to that of a bird scaled to the same body weight, but would increase exponentially as body mass increases. Although avian-like lung structure would be consistent with either a tachymetabolic-endothermic or a bradymetabolic-gigantothermic model, increasing body temperature requires adjustments to avoid overheating. We suggest that a unique sauropod structure/function unit facilitated the evolution of gigantism. This unit consisted of (1) a reduction in metabolic rate below that predicted by the body temperature, akin to thermal adaptation as seen in extant squamates, (2) presence of air-filled diverticula in the long neck and in the visceral cavity, and (3) low activity of respiratory muscles coupled with the high efficiency of cross-current gas exchange.

Electrical and mechanical activity in human respiratory muscles.

Electrical and mechanical activity in human respiratory muscles.

Selective inhibition of rem sleep-active pedunculopontine tegmental neurons suppresses respiratory network activity and REM sleep expression

Event Abstract Back to Event Selective inhibition of rem sleep-active pedunculopontine tegmental neurons suppresses respiratory network activity and REM sleep expression Kevin P. Grace1*, H. Liu1, 2 and Richard L. Horner1, 2 1 University of Toronto, Department of Physiology, Canada 2 University of Toronto, Department of Medicine, Canada Introduction: Rapid eye movement (REM) sleep is one of the three phenomenologically distinct and naturally occurring states of the mammalian central nervous system; associated with heightened neural activity and the inhibition of motor output pathways. During REM sleep, respiratory rate and variability are increased and the activity of certain respiratory muscles (e.g., genioglossus muscle of the tongue) is suppressed, with these changes defining the respiratory phenotype of REM sleep. Hypothesis: Based on several lines of new evidence which challenge the prevailing notion that pedunculopontine tegmental (PPT) neurons generate REM sleep, we hypothesize that selective inhibition of PPT REM sleep-active neurons will indicate that this cell group functions to suppresses REM sleep as well as shape its respiratory phenotype. Methods: This study used a combination of reverse microdialysis, electrophysiology, NADPH-diaphorase histochemistry and pharmacological methods in freely behaving rats (n=30) chronically instrumented for recording of sleep-wake states and respiratory muscle activities. Results: Bilateral perfusion of 8-OH-DPAT (10µM) into the PPT nuclei in order to selectively inhibit REM sleep-active neurons resulted in increased transitioning between sleep-wake states (P<0.001; normalized increase in transitions/hr = 76%) and a 15% reduction (P<0.001) of time spent in wakefulness predominantly accounted for by an increase in REM sleep. This increase in REM sleep propensity is reflected in the finding that the proportion of total sleep time occupied by REM sleep increased by 7.3% (P=0.017) during 8-OH-DPAT perfusion. Across all sleep-wake states, 8-OH-DPAT produced a significant increase in respiratory rate (P=0.003; mean increase = 7.3 breaths/min) and respiratory-related genioglossus activity (P=0.027; mean normalized increase = 69%). Given that a subset of PPT neurons are cholinergic, the latter effect may be due to withdrawal of direct cholinergic inhibition of the hypoglossal motor nucleus (HMN), which innervates the genioglossus muscle, since increasing endogenous acetylcholine at the HMN via microdialysis perfusion of an acetylcholinesterase inhibitor (100µM - eserine) resulted in significant suppression of respiratory-related genioglossus activity across sleep-wake states (P=0.008; mean normalized decrease = 56%). Conclusions: The PPT REM sleep-active cell population has a necessary role in shaping the phenotype of breathing via tonic suppression of respiratory rate and genioglossus muscle activity. Additionally, these neurons are critically involved in shaping sleep-wake state architecture; acting to suppress REM sleep, maintain wakefulness, and limit sleep-wake state transitioning. Current models regard the PPT nucleus as a generator of REM sleep on the basis of circumstantial evidence and therefore current models ought to be amended to reflect these direct findings. Acknowledgements: This research was supported by the CIHR K.G. is supported by a Graduate Studentship from the Ontario Thoracic Society Conference: B.R.A.I.N. platform in Physiology poster day 2009, Toronto, ON, Canada, 16 Dec - 16 Dec, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Grace KP, Liu H and Horner RL (2009). Selective inhibition of rem sleep-active pedunculopontine tegmental neurons suppresses respiratory network activity and REM sleep expression. Front. Neurosci. Conference Abstract: B.R.A.I.N. platform in Physiology poster day 2009. doi: 10.3389/conf.neuro.03.2009.17.033 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Dec 2009; Published Online: 17 Dec 2009. * Correspondence: Kevin P Grace, University of Toronto, Department of Physiology, Toronto, Canada, kevin.grace@utoronto.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kevin P Grace H. Liu Richard L Horner Google Kevin P Grace H. Liu Richard L Horner Google Scholar Kevin P Grace H. Liu Richard L Horner PubMed Kevin P Grace H. Liu Richard L Horner Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Stimulation of the rat medullary raphe nuclei induces differential responses in respiratory muscle activity

Neural control circuits that coordinate the motor activity of the diaphragm (DIA) and the geniohyoid muscle (GH) are potentially involved in pathological conditions such as various forms of sleep apnea. Here we investigated a differential role of the raphe magnus (RMg), pallidus (RPa) and the obscurus (ROb) nuclei in the neural control of DIA and GH muscle activity in rats under volatile anesthesia. In order to characterize a topographical organization of the raphe nuclei we analyzed changes in DIA and GH during high-frequency stimulation (HFS, 10-130 Hz, 60 micros pulse width, 40-160 microA, 30s). HFS of the RMg and the ROb induced apnea, in the latter case apnea was associated with massive tonic discharge in the GH. By contrast, HFS of the RPa induced tachypnea. At caudal stimulation sites the tachypnea was accompanied by tonic DIA activity and cessation of GH. These data suggest a differential distribution of inhibitory and excitatory drives of DIA and GH muscles within distinct raphe nuclei.

Relative impact of respiratory muscle activity on tidal flow and end expiratory volume in healthy neonates

It has been suggested that infants dynamically regulate their tidal flow and end-expiratory volume level. The interaction between muscle activity, flow and lung volume in spontaneously sleeping neonates is poorly studied, since it requires the assessment of transcutaneous electromyography of respiratory muscles (rEMG) in matched comparison to lung function measurements. After determining feasibility and repeatability of rEMG in 20 spontaneously sleeping healthy neonates, we measured the relative impact of intercostal and diaphragmatic EMG activity in direct comparison to the resulting tidal flow and FRC. We found good feasibility, repeatability and correlation of timing indices between rEMG activity and flow. The rEMG amplitude was significantly dependent on the resistive load of the face mask. Diaphragm and intercostal muscle activity commenced prior to the onset of flow and remained active during the expiratory cycle. The relative contribution of intercostal and diaphragmatic activity to flow was variable and changed dynamically. Using matched rEMG, air flow and lung volume measurements, we have found good feasibility and repeatability of intercostal and diaphragm rEMG measurements and provide the first quantitative measures of the temporal relationship between muscle activity and flow in spontaneously sleeping healthy neonates. Lung mechanical function is dynamically regulated and adapts on a breath to breath basis. So, non-invasive rEMG measurements alone or in combination with lung function might provide a more comprehensive picture of pulmonary mechanics in future studies. The data describing the timing of EMG and flow may be important for future studies of EMG triggered mechanical ventilation.

Evaluation of Respiratory Muscles Activity by Means of Cross Mutual Information Function at Different Levels of Ventilatory Effort

Analysis of respiratory muscles activity is an effective technique for the study of pulmonary diseases such as obstructive sleep apnea syndrome (OSAS). Respiratory diseases, especially those associated with changes in the mechanical properties of the respiratory apparatus, are often associated with disruptions of the normally highly coordinated contractions of respiratory muscles. Due to the complexity of the respiratory control, the assessment of OSAS related dysfunctions by linear methods are not sufficient. Therefore, the objective of this study was the detection of diagnostically relevant nonlinear complex respiratory mechanisms. Two aims of this work were: (1) to assess coordination of respiratory muscles contractions through evaluation of interactions between respiratory signals and myographic signals through nonlinear analysis by means of cross mutual information function (CMIF); (2) to differentiate between functioning of respiratory muscles in patients with OSAS and in normal subjects. Electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from three respiratory muscles: genioglossus, sternomastoid and diaphragm. Inspiratory pressure and flow were also acquired. All signals were measured in eight patients with OSAS and eight healthy subjects during an increased respiratory effort while awake. Several variables were defined and calculated from CMIF in order to describe correlation between signals. The results indicate different nonlinear couplings of respiratory muscles in both populations. This effect is progressively more evident at higher levels of respiratory effort.

Physiological and electromyographic responses during 40-km cycling time trial: Relationship to muscle coordination and performance

The purpose of this study was to compare the oxygen uptake (VO(2)), respiratory exchange ratio (RER), cadence and muscle activity during cycling a 40-km time trial (TT), and to analyse the relationship between muscle activity and power output (PO). Eight triathletes cycled a 40-km TT on their own bicycles, which were mounted on a stationary cycle simulator. The VO(2), RER and muscle activity (electromyography, EMG) from tibialis anterior (TA), gastrocnemius medialis (GA), biceps femoris (BF), rectus femoris (RF) and vastus lateralis (VL) of the lower limb were collected. The PO was recorded from the cycle simulator. The data were collected at the 3rd, 10th, 20th, 30th and 38th km. The root mean square envelope (RMS) of EMG was calculated. The VO(2) and PO presented a significant increase at the 38th km (45.23+/-8.35 ml kg min(-1) and 107+/-7.11% of mean PO of 40-km, respectively) compared to the 3rd km (38.12+/-5.98 ml kg min(-1) and 92+/-8.30% of mean PO of 40-km, respectively). There were no significant changes in cadence and RER throughout the TT. The VL was the only muscle that presented significant increases in the RMS at the 10th km (22.56+/-3.05% max), 20th km (23.64+/-2.52% max), 30th km (25.27+/-3.00% max), and 38th km (26.28+/-3.57%max) when compared to the 3rd km (21.03+/-1.88%max). The RMS of VL and RF presented a strong relationship to PO (r=0.89 and 0.86, respectively, p<0.05). The muscular steady state reported for cycling a 30-min TT seems to occur in the 40-km TT, for almost all assessed muscles, probably in attempt to avoid premature muscle fatigue.

Electromyographic activity of respiratory muscles: The possibility of considering diaphragmatic EMG as an isolated signal

Electromyographic activity of respiratory muscles: The possibility of considering diaphragmatic EMG as an isolated signal

Inspiratory muscle activity during incremental exercise in obese men

The aim of this study was to assess overall inspiratory muscle activity during incremental exercise in obese men and healthy controls using the non-invasive, inspiratory muscle tension-time index (T(T0.1)). We studied 17 obese subjects (mean age+/-s.d.; 49+/-13 years) and 14 control subjects (42+/-16) during an incremental, maximal exercise test. Measurements included anthropometric parameters, spirometry, breathing patterns and inspiratory muscle activity. T(T0.1) was calculated using the equation T(T0.1)=P(0.1)/P(Imax) x T(I)/T(TOT) (where P(0.1) is mouth occlusion pressure, P(Imax) is maximal inspiratory pressure and T(I)/T(TOT) is the duty cycle). At same levels of maximal exercise (%W(max)) (20, 40, 60, 80, 100% W(max)), obese subjects showed higher P(0.1) (P<0.001) and P(0.1)/P(Imax) (P<0.001) values than controls. T(T0.1) was thus higher in obese subjects for each workload increment and at maximal exercise (P<0.001). During exercise, patients with obesity show alterations in inspiratory muscle activity as a result of both reduced inspiratory strength (as measured by maximal inspiratory pressure) and increased ventilatory drive (as reflected by mouth occlusion pressure), which prone obese subject to respiratory muscle weakness. Our results suggest that impaired respiratory muscle activity could contribute to a decrease in exercise capacity. T(T0.1) may be useful in our understanding concerning the benefits of endurance training.

Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis

Patients with sepsis in the ICU (intensive care unit) are characterized by skeletal muscle wasting. This leads to muscle dysfunction that also influences the respiratory capacity, resulting in prolonged mechanical ventilation. Catabolic conditions are associated with a general activation of the ubiquitin-proteasome pathway in skeletal muscle. The aim of the present study was to measure the proteasome proteolytic activity in both respiratory and leg muscles from ICU patients with sepsis and, in addition, to assess the variation of proteasome activity between individuals and between duplicate leg muscle biopsy specimens. When compared with a control group (n=10), patients with sepsis (n=10) had a 30% (P<0.05) and 45% (P<0.05) higher proteasome activity in the respiratory and leg muscles respectively. In a second experiment, ICU patients with sepsis (n=17) had a 55% (P<0.01) higher proteasome activity in the leg muscle compared with a control group (n=10). The inter-individual scatter of proteasome activity was larger between the patients with sepsis than the controls. We also observed a substantial intra-individual difference in activity between duplicate biopsies in several of the subjects. In conclusion, the proteolytic activity of the proteasome was higher in skeletal muscle from patients with sepsis and multiple organ failure compared with healthy controls. It was shown for the first time that respiratory and leg muscles were affected similarly. Furthermore, the variation in proteasome activity between individuals was more pronounced in the ICU patients for both muscle types, whereas the intra-individual variation between biopsies was similar for ICU patients and controls.

Respiratory motor activity: influence of neuromodulators and implications for sleep disordered breathingThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigators' Forum.

Sleep, especially rapid-eye-movement sleep, causes fundamental modifications of respiratory muscle activity and control mechanisms, modifications that can predispose individuals to sleep-related breathing disorders. One of the most common of these disorders is obstructive sleep apnea (OSA) that affects approximately 4% of adults. OSA is caused by repeated episodes of pharyngeal airway obstruction that can occur hundreds of times per night, leading to recurrent asphyxia, arousals from sleep, daytime sleepiness, and adverse cardiovascular and cerebrovascular consequences. OSA is caused by the effects of sleep on pharyngeal muscle tone in individuals with already narrow upper airways. Moreover, since OSA occurs only in sleep, this disorder by definition is a state-dependent process ultimately caused by the influence of sleep neural mechanisms on the activity of pharyngeal motoneurons. This review synthesizes recent findings relating to control of pharyngeal muscle activity across sleep-wake states, with special emphasis on the influence of neuromodulators acting at the hypoglossal motor nucleus that inervates the genioglossus muscle of the tongue. The results of such basic physiological studies may be relevant to identifying and developing new pharmacological strategies to augment pharyngeal muscle activity in sleep, especially rapid-eye-movement sleep, as potential treatments for OSA.

REBUTTAL FROM DR. BRENGELMANN

POINT-COUNTERPOINTREBUTTAL FROM DR. BRENGELMANNPublished Online:01 Nov 2006https://doi.org/10.1152/japplphysiol.00698c.2006MoreSectionsPDF (35 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Point of agreement:the utility of combining open-loop cardiac and vascular subsystem properties in analyses of cardiovascular stability. For the heart, Pra ↑→ F ↑; for the vasculature, F ↑→ Pra ↓. Connected, they form a negative feedback system that stabilizes at the Pra that causes the heart to pump out the F that causes that Pra. Showing this graphically requires plotting one of the relationships with its independent variable on the y-axis.“Waterfall” relevance?Yes, resistance of a vascular segment or Starling resistor increases as it collapses. But, the (Pms−Pra)/Rv concept applies only to the sloped segment of venous return curves, for which intravascular pressures are positive and apparent Rv is constant, i.e., no vessel collapse. About waterfalls: 1) flow depends only on the flow arriving at the precipice edge; 2) transport to the lower level is due to gravity; and 3) they are not enveloped by flexible elastic walls. Why are we talking about them?Bathtub analogous?In Magder's Fig. 1A, (1) we see the right atrium at the level of the water surface and Pra labeled as equal to MSFP (my Pms). But surface level pressure has to be zero, i.e., equal to atmospheric (Patm). Just as the Fig. 1A tub cartoon does not correspond to the pressures marked on the graph below it, the hydrostatic relationships are incorrect in the other panels (e.g., pressure at the atrium level would be greater than any in the tub). Correcting all pressures to the same level would reveal the pressure gradient associated with flow, but why pursue this? The (Pms−Pra)/Rv concept is not about blood flowing downhill, and flow in the defining experiments was certainly not driven by gravity. And that faucet? How does it know the flow needed to keep the tub full?MSFP (Pms) energy source?Quantitatively, the elastic work that moves blood out of a compartment equals the integral of instantaneous pressure times compartment volume decrement dV. Magder's compartment at Pms, kept at constant volume for steady states, has no dV. No dV, no energy release.To Magder's “what makes the blood go around?” (1, first sentence), I reply not elastic energy from a compartment at Pms; but the work manifested in the integral of P times dV for the ventricles (ignoring for the purposes of the present argument the energy input by vessel compression and expansion due to activity of skeletal and respiratory muscles).REFERENCE1 Magder S. Point: The classical Guyton view that mean systemic pressure, right atrial pressure, and venous resistance govern venous return is correct. J Appl Physiol. In press.Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByAn analytical perspective on the venous return controversy7 June 2018 | Canadian Journal of Anesthesia/Journal canadien d'anesthésie, Vol. 65, No. 9Understanding Guyton's venous return curvesDaniel A. Beard, and Eric O. Feigl1 September 2011 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. 301, No. 3 More from this issue > Volume 101Issue 5November 2006Pages 1527-1527 Copyright & PermissionsCopyright © 2006 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00698c.2006History Published online 1 November 2006 Published in print 1 November 2006 Metrics Downloaded 288 times