Rat model of chronic recurrent airway obstructions to study the sleep apnea syndrome

STUDY OBJECTIVES: To implement a chronic rat model of recurrent airway obstructions to study the obstructive sleep apnea (OSA) syndrome. DESIGN: Prospective controlled animal study. SETTING: University laboratory. PATIENTS OR PARTICIPANTS: 24 male Sprague-Dawley rats (250-300 g). INTERVENTIONS: The rats were placed in a setup consisting of a body chamber and a head chamber separated by a neck collar specially designed to apply recurrent airway obstructions with OSA patterns. Rats in the Obstruction group (n=8) were subjected to 5-s obstructions at a rate of 60 per hour, 6 h/day during 4 weeks. Sham rats (n=8) were placed in the setup but no obstructions were applied. Naive rats (n=8) were subjected to no intervention. MEASUREMENTS AND RESULTS: Breathing flow, pressure, CO2 air concentration, and SpO2 showed that the model mimicked OSA respiratory events (obstructive apneas, increased respiratory efforts, and oxygen saturation dips). Animal stress, assessed by body weight and plasma corticosterone, was not significantly different across Obstruction and Sham groups. This supports the concept that this novel model does not introduce a significant burden of stress in the rat after acclimatization to the chamber. Thromboxane-B2/6-keto-Prostaglandin-Flalpha ratio in plasma, which is an index of vasoconstriction, was significantly increased in the rats subjected to obstructions. CONCLUSIONS: The designed animal model of chronic recurrent airway obstructions is feasible and potentially useful to study the mechanisms involved in the cardiovascular consequences of OSA.     

Electromyographic activity at the base and tip of the tongue across sleep–wake states in rats

Obstructive sleep apnea (OSA) patients have elevated tonic and phasic inspiratory activity in the genioglossus and other upper airway muscles during wakefulness; this protects their upper airway from collapse. In this group, sleep-related decrements of upper airway motor tone result in sleep-related upper airway obstructions. We previously reported that in the rat, a species widely used to study the neural mechanisms of both sleep and breathing, lingual electromyographic activity (EMG) is minimal or absent during slow-wave sleep (SWS) and then gradually increases after the onset of rapid eye movement sleep (REMS) due to the appearance of large phasic bursts. Here, we investigated whether sleep–wake patterns and respiratory modulation of lingual EMG depend on the site of EMG recording within the tongue. In nine chronically instrumented rats, we recorded from 17 sites within the tongue and from the diaphragm across sleep–wake states. We quantified lingual EMG in successive 10 s intervals of continuous 2 h recordings (1–3 p.m.). We found that sleep–wake patterns of lingual EMG did not differ between the base and tip of the tongue, and that respiratory modulation was extremely rare regardless of the recording site. We also determined that the often rhythmic lingual bursts during REMS do not occur with respiratory rhythmicity. This pattern differs from that in OSA subjects who, unlike rats, have collapsible upper airway, exhibit prominent respiratory modulation of upper airway motor tone during quiet wakefulness, retain considerable tonic and inspiratory phasic activity during SWS, and show nadirs of activity during REMS.     

Leptin receptor expression in the dorsomedial hypothalamus stimulates breathing during NREM sleep in db/db mice

Study ObjectivesObesity leads to obstructive sleep apnea (OSA), which is recurrent upper airway obstruction during sleep, and obesity hypoventilation syndrome (OHS), hypoventilation during sleep resulting in daytime hypercapnia. Impaired leptin signaling in the brain was implicated in both conditions, but mechanisms are unknown. We have previously shown that leptin stimulates breathing and treats OSA and OHS in leptin-deficient ob/ob mice and leptin-resistant diet-induced obese mice and that leptin’s respiratory effects may occur in the dorsomedial hypothalamus (DMH). We hypothesized that leptin receptor LepR^b-deficient db/db mice have obesity hypoventilation and that restoration of leptin signaling in the DMH will increase ventilation during sleep in these animals.MethodsWe measured arterial blood gas in unanesthetized awake db/db mice. We subsequently infected these animals with Ad-LepR^b or control Ad-mCherry virus into the DMH and measured ventilation during sleep as well as CO₂ production after intracerebroventricular (ICV) infusions of phosphate-buffered saline or leptin.ResultsAwake db/db mice had elevated CO₂ levels in the arterial blood. Ad-LepR^b infection resulted in LepR^b expression in the DMH neurons in a similar fashion to wildtype mice. In LepR^b-DMH db/db mice, ICV leptin shortened REM sleep and increased inspiratory flow, tidal volume, and minute ventilation during NREM sleep without any effect on the quality of NREM sleep or CO₂ production. Leptin had no effect on upper airway obstruction in these animals.ConclusionLeptin stimulates breathing and treats obesity hypoventilation acting on LepR^b-positive neurons in the DMH.     

Increased load on the respiratory muscles in obstructive sleep apnea

We wished to quantify, in patients with obstructive sleep apnoea (OSA), the activity of the respiratory muscles in relation to upper airway occlusion and patency in sleep. We hypothesized that particular levels of neuromuscular activation are directly associated with upper airway patency. 21 patients with previously diagnosed OSA and 21 healthy control subjects underwent respiratory muscle testing and polysomnography. Neural respiratory drive, as measured by the electromyogram of the diaphragm (EMG_di) was elevated in the obese OSA patients, awake and supine (13.1(5.6)%max), compared to normal subjects (mean (SD) 8.1(2.3)%max, p < 0.01). During unobstructed breathing in sleep (stage N2) normal subjects had an EMG_di of 7.7(3.9) compared to 22.8(19.2)%max in the OSA group (p < 0.001). Prior to airway occlusion, EMG_{submandibular} and EMG_di dropped markedly, and then, following occlusion, increased progressively to their highest levels at airflow onset. Patients with OSA require specific and increased levels of neural respiratory drive to sustain ventilation in sleep.     

Airway Dilator Muscle Activity and Lung Volume During Stable Breathing in Obstructive Sleep Apnea

Study Objectives:

Many patients with obstructive sleep apnea (OSA) have spontaneous periods of stable flow limited breathing during sleep without respiratory events or arousals. In addition, OSA is often more severe during REM than NREM and more severe during stage 2 than slow wave sleep (SWS). The physiological mechanisms for these observations are unknown. Thus we aimed to determine whether the activity of two upper airway dilator muscles (genioglossus and tensor palatini) or end-expiratory lung volume (EELV) differ between (1) spontaneously occurring stable and cyclical breathing and (2) different sleep stages in OSA.

Design:

Physiologic observation.

Setting:

Sleep physiology laboratory.

Study Participants:

15 OSA patients with documented periods of spontaneous stable breathing.

Intervention:

Subjects were instrumented with intramuscular electrodes for genioglossus and tensor palatini electromyograms (EMG_GG and EMG_TP), chest and abdominal magnetometers (EELV measurement), an epiglottic pressure catheter (respiratory effort), and a mask and pneumotachograph (airflow/ventilation). Patients slept supine overnight without CPAP.

Measurements and Results:

Peak and Tonic EMG_GG were significantly lower during cyclical (85.4 ± 2.7 and 94.6 ± 4.7 % total activity) than stable breathing (109.4 ± 0.4 and 103 ± 0.8 % total activity, respectively). During respiratory events in REM, tonic EMG_GG activity was lower than during respiratory events in stage 2 (71.9 ± 5.1 and 119.6 ± 5.6 % total activity). EMG_GG did not differ between stable stage 2 and stable SWS (98.9 ± 3.2 versus 109.7 ± 4.4 % total activity), nor did EMG_TP or EELV differ in any breathing condition/sleep stage.

Conclusions:

Increased genioglossus muscle tone is associated with spontaneous periods of stable flow limited breathing in the OSA subjects studied. Reductions in genioglossus activity during REM may explain the higher severity of OSA in that stage. Increased lung volume and tensor palatini activity do not appear to be major mechanisms enabling spontaneous stable flow limited breathing periods.

Citation:

Jordan AS; White DP; Lo YL; Wellman A; Eckert DJ; Yim-Yeh S; Eikermann M; Smith SA; Stevenson KE; Malhotra A. Airway dilator muscle activity and lung volume during stable breathing in obstructive sleep apnea. SLEEP 2009;32(3):361–368.     

Assessment of upper airway mechanics during sleep

Obstructive sleep apnea, which is the most prevalent sleep breathing disorder, is characterized by recurrent episodes of upper airway collapse and reopening. However, the mechanical properties of the upper airway are not directly measured in routine polysomnography because only qualitative sensors (thermistors for flow and thoraco-abdominal bands for pressure) are used. This review focuses on two techniques that quantify upper airway obstruction during sleep. A Starling model of collapsible conduit allows us to interpret the mechanics of the upper airway by means of two parameters: the critical pressure (P_crit) and the upstream resistance (R_up). A simple technique to measure P_crit and R_up involves the application of different levels of continuous positive airway pressure (CPAP) during sleep. The forced oscillation technique is another non-invasive procedure for quantifying upper airway impedance during the breathing cycle in sleep studies. The latest developments in these two methods allow them to be easily applied on a routine basis in order to more fully characterize upper airway mechanics in patients with sleep breathing disorders.     

Determinants of Ventilatory Instability in Obstructive Sleep Apnea: Inherent or Acquired?

Study Objectives:

Certain respiratory control characteristics determine whether patients with collapsible upper airway develop stable or unstable breathing during sleep, thereby influencing the severity of obstructive apnea (OSA). These include arousal threshold (T_A), response to transient hypoxia and hypercapnia (Dynamic Response) and the increase in respiratory drive required for arousal-free airway opening (T_ER). We wished to determine whether these characteristics are inherent or are acquired during untreated OSA.

Design:

T_A, Dynamic Response, and T_ER were measured in patients with severe OSA before and after treatment with continuous positive airway pressure (CPAP). Changes observed after treatment were deemed to have been acquired during untreated OSA.

Setting:

University-based sleep laboratory.

Patients:

15 patients with severe OSA.

Interventions:

(1) 30-sec alterations in inspired gases during sleep on CPAP. (2) Brief dial-downs of CPAP (dial-downs) both during air breathing and when ventilation was increased to different levels.

Measurements and Results:

T_A: the increase in ventilation associated with a 50% probability of arousal (T_A50). Dynamic Response: the increase in ventilation on the 5th breath following breathing 3% CO₂ in 11% to 15% O₂. T_ER: the increase in ventilation prior to dial-downs that was associated with an arousal-free airway opening during dial-down. CPAP therapy (10.5 ± 4.3 months) resulted in marked reduction in Dynamic Response (131% ± 95% to 52% ± 34% baseline ventilation, P < 0.005), a decrease in T_A50 (134% ± 78% to 86% ± 47% baseline ventilation, P < 0.05), and no change in T_ER.

Conclusions:

T_ER may be an inherent characteristic. Untreated OSA results in an increase in dynamic response to asphyxia and an increase in arousal threshold.

Citation:

Loewen A; Ostrowski M; Laprairie J; Atkar R; Gnitecki J; Hanly P; Younes M. Determinants of Ventilatory Instability in Obstructive Sleep Apnea: Inherent or Acquired? SLEEP 2009;32(10):1355-1365.     

Upper airway collapsibility evaluated by a negative expiratory pressure test in severe obstructive sleep apnea

OBJECTIVES:

To investigate the usefulness of measuring upper airway collapsibility with a negative expiratory pressure application as a screening test for severe obstructive sleep apnea (OSA).

INTRODUCTION:

OSA is a risk factor for cardiovascular disease, and it may have serious consequences. Its recognition may have important implications during the perioperative period. Increased upper airway collapsibility is one of the main determinants of OSA, and its evaluation could be useful for identifying this condition.

METHODS:

Severe OSA and normal subjects (24 in each group) were matched by body mass index and referred to our sleep laboratory. The subjects were enrolled in an overnight sleep study, and a diurnal negative expiratory pressure test was performed. Flow drop (ΔV̇) and expiratory volume were measured in the first 0.2 s (V_0.2) of the negative expiratory pressure test.

RESULTS:

ΔV̇ and V_0.2 (%) values were statistically different between normal and OSA subjects. OSA patients showed a greater decrease in flow than normal subjects. In addition, severely OSA patients exhaled during the first 0.2 s of the negative expiratory pressure application was an average of only 11.2% of the inspired volume compared to 34.2% for the normal subjects. Analysis of the receiver operating characteristics showed that V_0.2 (%) and ΔV̇ could accurately identify severe OSA in subjects with sensitivities of 95.8% and 91.7%, respectively, and specificities of 95.8% and 91.7%, respectively.

CONCLUSIONS:

V_0.2 (%) and ΔV̇ are highly accurate parameters for detecting severe OSA. The pharyngeal collapsibility measurement, which uses negative expiratory pressure during wakefulness, is predictive of collapsibility during sleep.     

Schlafbezogene Atmungsst?rungen und Vorhofflimmern

Sleep-disordered breathing is one of the most common sleep disorders. Especially obstructive sleep apnea (OSA) is an independent cardiovascular risk factor. Clinical studies have proven a significant association between OSA and atrial fibrillation, the most common cardiac arrhythmia. Currently, there is no proven evidence for causality. Untreated OSA seems to be a risk factor for failure of rhythm control strategy in atrial fibrillation. The recurrence rate after cardioversion is higher in case of additional untreated OSA. Continuous positive airway pressure (CPAP) therapy in OSA patients could reduce relapse rate. However, there is a lack of randomized controlled clinical trials with defined end points on this topic. A specific sleep medicine interview as well as sleep studies with portable monitoring and cardiorespiratory polysomnography are recommended when sleep-disordered breathing is suspected. Procedures for the management of patients with atrial fibrillation are given.     

Complex sleep apnea and obesity hypoventilation syndrome. Opposite ends of the spectrum of obstructive sleep apnea?

In most cases, the application of continuous positive airway pressure (CPAP) during sleep in patients affected by obstructive sleep apnea (OSA) eliminates upper airway obstruction and makes breathing stable and regular. However, some OSA patients develop periodic breathing and central apneas during CPAP administration, a finding that has been labelled as “complex sleep apnea” (complex SA). Such breathing disorder may occur only acutely after CPAP treatment initiation or sometimes persist with chronic CPAP treatment. We hypothesize that complex SA may be the consequence of mechanisms analogous to those leading to obesity hypoventilation syndrome (OHS), but operating in an opposite direction.Periodic breathing is one of the factors predisposing to OSA and is an essential factor for the recurrence of central apneas in normo or hypocapnic patients. A high ventilatory responsiveness to chemical stimuli enhances breathing periodicity. In subjects with periodic central apneas chemoresponsiveness is high, while in subjects with OSA it spans throughout a wide range, and is correlated to diurnal blood gas levels. In fact, sleep respiratory disorders may be responsible for either an augmentation in ventilatory responses to chemical stimuli consequent to chronic exposure to intermittent hypoxia, or for a decrease in ventilatory responses when prolonged exposure to hypercapnia is experienced. Among OSA subjects, those with OHS show very depressed hypercapnic responses. After chronic OSA treatment, ventilatory responses to chemical stimuli may either decrease, in previously hyperresponsive subjects, or increase, in previously hyporesponsive subjects. Most patients with OHS decrease daytime PCO₂ levels and increase their ventilatory responses after chronic CPAP treatment.Complex SA could appear in those OSA subjects in whom chronic exposure to nocturnal respiratory disorders leads to the highest responsiveness to chemical stimuli, and could disappear after blunting of ventilatory responses following chronic CPAP treatment. Complex SA may be one extreme of evolutionary spectrum of OSA, the opposite end being represented by OHS.     

Prevention of airway obstructions during sleep in infants with breath-holding spells by means of oral belladonna: a prospective double-blind crossover evaluation.

We investigated whether the brief airway obstructions seen during sleep in infants with breath-holding spells were controlled by the autonomic nervous system. We studied 20 infants, with a history of breath-holding spells and a median age of 12 wk (range 4-46 wk). During sleep they had a median of 6 airway obstructions per 10-hr recording (range 3-16 events), with a median duration of 8 sec (range 4-12 sec). No explanation was found for the airway obstructions. In every infant, a double-blind crossover challenge was conducted. It included oral administration of tincture of belladonna, equivalent to 0.01 mg/kg weight of atropine, and placebo syrup containing no belladonna. The belladonna, or the placebo, was administered at bedtime for 7 days, followed by a 7-day washout period. Another 7-day series of syrup administration was then undertaken. A nighttime polygraphic recording was made after each 7-day series. It was the belladonna, and not the placebo, that induced the disappearance of the obstructions in 10 infants; these were called "drug responsive". In 5 children no effect was observed after either the placebo or belladonna; these infants were defined as "drug unresponsive". In 4 subjects the obstructions disappeared after both belladonna and the placebo; the children were considered to have an "inconclusive response". One infant was excluded from the study because he developed an airway infection. It is concluded that in some breath-holding infants, obstructed breathing episodes during sleep disappear after the administration of an atropinic drug. The observation could indicate a role of the autonomic nervous system in the control of the upper airways during sleep in infants.     

Schlafbezogene Atmungsstörungen und zerebrovaskuläre Erkrankungen

Sleep-related breathing disorders comprise obstructive sleep apnea (OSA), central sleep apnea (CSA), Cheyne–Stokes respiration (CSR), and central alveolar hypoventilation. OSA is significantly associated with known cardiovascular risk factors, e.g., arterial hypertension, atrial fibrillation, and carotid atheromatosis. In addition, OSA has been shown to independently increase stroke risk. Thus, OSA is a direct and indirect risk factor of ischemic stroke, and early diagnosis and treatment of OSA may be crucial for stroke prevention. Acute ischemic stroke may cause any type of sleep-related breathing disorder in an affected patient. Nocturnal breathing abnormalities may be present transiently or persist for a longer period of time, affecting both neurological outcome and the risk of recurrent stroke. Sleep-disordered breathing is highly prevalent in patients with large supratentorial or bihemispheric infarctions, brainstem and cerebellar infarctions. It is associated with worse prognosis, increased disability, and higher mortality. Recently, several interventional studies showed that early implementation of continuous positive airway pressure (CPAP) treatment overnight is feasible and significantly improves neurological outcome in patients with ischemic stroke even if overall mortality may not be significantly reduced.     

Factors affecting respiratory system stability

Periodic breathing (recurrent central apneas) occurs frequently during sleep. Periodic breathing can arise as a result of unstable behavior of the respiratory control system. A mathematical model of the respiratory control system was used to investigate, systematically, the effect of severity of disturbances to respiration and certain system parameters on periodic breathing occurring during sleep. The model consisted of multi-compartment representation of O₂ and CO₂ stores, a peripheral controller sensitive to O₂ and CO₂, and a central controller sensitive to CO₂. The effects of hypoxia and hypercapnia on the upper airway muscles were not considered in the model. Episodes of hyperventilation or asphyxia were used to disturb the control system and explore the boundaries of stable breathing. Circulation time and metabolic rate were also varied. Simulations with the model produced the following findings: The number of central apneas associated with periodic breathing were greater as circulation time increased; controller gain increases also made the number of apneas greater, although periodic breathing occurs with lower controller gains as circulation time increases. At each level of circulation time there was a range of controller gain changes which caused little change in the number of apneas. There were more apneas with hypoxia; also the number of apneas increased with sleep-associated reductions in metabolic rate. The more rapidly resting PCO₂ rose at sleep onset, the greater the likelihood of recurrent apneas. Finally, the more intense the disturbance, the more apneas there were.     

Effects of nasal pathologies on obstructive sleep apnea

Increased airway resistance can induce snoring and sleep apnea, and nasal obstruction is a common problem in snoring and obstructive sleep apnea (OSA) patients. Many snoring and OSA patients breathe via the mouth during sleep. Mouth breathing may contribute to increased collapsibility of the upper airways due to decreased contractile efficiency of the upper airway muscles as a result of mouth opening. Increased nasal airway resistance produces turbulent flow in the nasal cavity, induces oral breathing, promotes oscillation of the pharyngeal airway and can cause snoring.     

Sleep‐disordered breathing in children with pycnodysostosis

Upper airway obstruction is a common feature in pycnodysostosis and may cause obstructive sleep apnea (OSA). The aim of our study was to analyze sleep‐disordered breathing and respiratory management in children with pycnodysostosis. A retrospective review of the clinical charts and sleep studies of 10 consecutive children (three girls and seven boys) with pycnodysostosis seen over a time period of 10 years was performed. Six patients had severe OSA and/or nocturnal hypoventilation and were started on continuous positive airway pressure (CPAP) as a first treatment at a median age of 3.4 ± 2.6 years, because of the lack of indication of any surgical treatment. Three patients could be weaned after several years from CPAP after spontaneous improvement (two patients) or multiple upper airway surgeries (one patient). Three patients had upper airway surgery prior to their first sleep study with two patients still needing CPAP during their follow‐up. Only one patient never developed OSA. Patients with pycnodysostosis are at a high risk of severe OSA, underlying the importance of a systematic screening for sleep‐disordered breathing. Multidisciplinary care is mandatory because of the multilevel airway obstruction. CPAP is very effective and well accepted for treating OSA.     

Mechanisms of sleep-disordered breathing: causes and consequences

Obstructive sleep apnea (OSA) is very common in the general population and is characterized by ineffective inspiratory efforts against a collapsed upper airway during sleep. Collapse occurs mainly at the level of the velopharynx and oropharynx due to a combination of predisposing anatomy and the withdrawal of pharyngeal dilator activity during sleep. Central sleep apnea (CSA) is a manifestation of chemoreflex control instability, leading to periods of inadequate respiratory drive sufficient to trigger breathing, usually alternating with periods of hyperventilation. While both forms of apnea are the result of differing pathophysiology, it has become increasingly clear that OSA and CSA often coexist in the same patient, the existence of one can predispose to the other, and that the two are not as distinct as previously thought. Both OSA and CSA exert a number of acute deleterious effects including intermittent hypoxia, arousals from sleep, and swings in negative intrathoracic pressure, which in turn lead to chronic physiologic consequences such as autonomic dysregulation, endothelial dysfunction, and cardiac remodeling. These underlying pathophysiological mechanisms provide a framework for understanding why OSA and CSA may predispose to cardiovascular diseases like ischemic heart disease and stroke.     

Is there a link between intermittent hypoxia-induced respiratory plasticity and obstructive sleep apnoea?

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 models 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). Long-term facilitation has been studied most frequently in rats, and exhibits interesting properties consistent with a role in stabilizing breathing during sleep. Specifically, 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 and 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 and 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.     

The effect of acute exposure to morphine on breathing variability and cardiopulmonary coupling in men with obstructive sleep apnea: A randomized controlled trial

Opioid‐related deaths from respiratory depression are increasing but there is only limited information on the effect of morphine on breathing during sleep. This study aimed to detect and quantify opioid‐induced cardiorespiratory pattern changes during sleep in obstructive sleep apnea (OSA) patients using novel automated methods and correlate these with conventional polysomnography (PSG) measures. Under a randomized double‐blind placebo‐controlled crossover design, 60 male OSA patients attended two one‐night visits to the sleep laboratory, at least a week apart. Either a 40‐mg controlled‐release oral morphine dose or placebo was administered. Breathing during sleep was measured by standard in‐laboratory PSG. We analysed the inter‐breath interval (IBI) from the PSG flow channel to quantify breathing irregularity. Cardiopulmonary coupling (CPC) was analysed using the PSG electrocardiogram (ECG) channel. Following the consumption of morphine, the 60 OSA patients had fewer breaths (p = .0006), a longer inter‐breath interval (p < .0001) and more irregular breathing with increased IBI coefficient of variation (CV) (p = .0015) compared to the placebo night. A higher CPC sleep quality index was found with morphine use. The change of key IBI and CPC parameters was significantly correlated with the change of key PSG sleep‐disordered breathing parameters. In conclusion, 40 mg controlled‐release morphine resulted in a longer breathing cycle and increased breathing irregularity but generally more stable sleep in OSA patients. The significant links between the IBI and CPC techniques and a range of PSG sleep‐disordered breathing parameters may suggest a practical value as surrogate overnight cardiorespiratory measurements, because both respiratory flow and ECG can be detected by small portable devices.     

Schlafbezogene Atmungsstörungen bei Parkinsonsyndromen: Häufigkeit, Art und Behandlungsansätze

Objective

In recent literature the contribution of sleep related breathing disorders [SRBD] to the complex sleep disorder of Parkinson's disease [PD] patients is controversely discussed. In our study we discovered the frequency and kind of SRBD in a group of PD patients with sleep complaints.

Patients and methods

83 patients with different types of parkinsonism were studied polysomnographically. Respiration was measured by means of inductance plethysmography, capnography, and pulse oximetry. Different analysing techniques were used. Besides the evaluation of apneas and hypopneas a visual classification of the respiratory pattern and a breath-to-breath calculation of the laboured breathing index [LBI] was carried out.

Results

More than 50% of the patients showed sleep disordered breathing. Most of them had upper airway obstructions. Central apnea was observed in 5 cases, three of those suffered from a heart disease. In 25% the SRBD should be treated. The LBI calculation revealed hints for short pharyngeal obstructions in each patient. This parameter turned out to be highly sensitive to detect changes in upper airway mechanics and was therefore considered to be useful in testing dopaminergic influences on respiratory movements.

Conclusion

Disturbances of the extrapyramidal motor system may lead to long lasting obstructive hypoventilation of different clinical importance. Specific measurement techniques should be used to identify these disturbances. The laboured breathing index may be useful to detect dopaminergic deficits in respiratory motion. As more than 50% of severe SRBD patients are not able to handle nCPAP it is necessary to develop pharmacological options. Dopaminergic medication as a possible therapeutical alternative to nCPAP should be tested in further studies.     

Does episodic hypoxia affect upper airway dilator muscle function? Implications for the pathophysiology of obstructive sleep apnoea

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.