Monitoring respiratory function and sleep in the obese Vietnamese pot-bellied pig.

Development of drug treatments for obstructive sleep-disordered breathing has been impeded by the lack of animal models. The obese pig may be a suitable animal model, as it has been reported to experience sleep-disordered breathing resembling human obstructive sleep apnea. The purpose of this paper is to describe in detail techniques for chronic instrumentation of the obese Vietnamese pot-bellied pig and to study respiratory function during sleep. Under general anesthesia, four obese pigs were instrumented for long-term recording of intrapleural and tracheal pressures, genioglossal EMG, and bioelectric signals related to sleep. A custom-fitted face mask was used to record respiratory variables including airflow, snoring, and expired CO(2). Most chronic instrumentation provided robust signals for up to 6 wk after installation. All pigs displayed sleep-disordered breathing characterized by increased resistance to airflow, snoring, inspiratory flow limitation, and possible sleep disruption. Apneas and hypopneas were not a feature of breathing during sleep in these animals. Nonetheless, this animal preparation may be useful for exploring possible drug treatments for obstructive sleep-disordered breathing.     

Relationship between sleep postures and sleep-disordered breathing parameters in people with Down syndrome in Japan

Sleep and Biological Rhythms - People with Down syndrome (DS) are prone to develop sleep-disordered breathing (SDB), especially obstructive sleep apnea (OSA) and they are reported to sleep in...     

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020

Sleep and Biological Rhythms - The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously...     

Obstructive sleep apnea and vascular disease

There is emerging evidence linking obstructive sleep apnea (OSA) to vascular disease, including hypertension. This relationship may be independent of co-morbidity, such as obesity. Even apparently healthy OSA patients have evidence of subtle functional vascular abnormalities that are known to occur in patients with hypertension and atherosclerosis. Untreated OSA may possibly contribute to the initiation and/or progression of pathophysiologic mechanisms involved in hypertension, heart failure, cardiac ischemia and stroke. This brief commentary will examine the evidence and mechanisms linking OSA to vascular disease.     

Dynamic ventilatory response to CO(2) in congestive heart failure patients with and without central sleep apnea.

Nonobstructive (i.e., central) sleep apnea is a major cause of sleep-disordered breathing in patients with stable congestive heart failure (CHF). Although central sleep apnea (CSA) is prevalent in this population, occurring in 40-50% of patients, its pathogenesis is poorly understood. Dynamic loop gain and delay of the chemoreflex response to CO(2) was measured during wakefulness in CHF patients with and without CSA by use of a pseudorandom binary CO(2) stimulus method. Use of a hyperoxic background minimized responses derived from peripheral chemoreceptors. The closed-loop and open-loop gain, estimated from the impulse response, was three times greater in patients with nocturnal CSA (n = 9) than in non-CSA patients (n = 9). Loop dynamics, estimated by the 95% response duration time, did not differ between the two groups of patients. We speculate that an increase in dynamic gain of the central chemoreflex response to CO(2) contributes to the genesis of CSA in patients with CHF.     

心源性睡眠呼吸异常：心衰患者睡眠期间陈-施呼吸 机制探讨的初步报告*

目的: 探讨心衰患者陈施呼吸的发生率及发生机制。方法: 连续入选2015年3月~2015年5月于阜外医院行睡眠呼吸监测的患者56例,分为心衰组和非心衰组。结果: 两组睡眠呼吸暂停的发生率均较高,心衰组11例患者中呼吸暂停低通气指数（AHI）>5的有10例,平均AHI指数23.93±14.63;非心衰组45例患者中AHI>5的有33例,平均AHI指数16.20±18.76;心衰组中枢性睡眠呼吸暂停（CSA）次数占睡眠呼吸暂停总数的比例明显大于非心衰组病人,分别为80.21%±30.55%和27.16%±35.71%,P<0.01。结论: 心脏的循环功能和肺脏的呼吸功能是联合一体化,相互联系、互为因果而又互相影响。慢性心力衰竭的循环障碍促成了潮式呼吸的发生,所以称之为心源性呼吸睡眠异常。     

Changes in the Cardiovascular Function in Healthy Subjects and Patients with Ischemic Heart Disease during Sleep

The purpose of this study was to investigate the autonomic regulation of the cardiovascular system during sleep in health and disease. The examination included 396 subjects: 29 healthy subjects and 367 patients with ischemic heart disease, of whom 149 had left-ventricular failure and 214 hypertension. Sleep quality and the presence of obstructive sleep apnea syndrome were evaluated by polysomnography; the character of autonomic regulation of cardiac rhythm and hemodynamics was determined by computerized testing during night sleep and an active orthostatic test immediately before and after sleep. The results permitted the authors to conclude that autonomic regulation may be restored to various degrees in health and disease, depending on the pathology level. The sleep quality influenced the restoration of hemodynamics more than that of the cardiac rhythm, mainly when obstructive sleep apnea syndrome was present.     

The English bulldog: a natural model of sleep-disordered breathing

To establish a natural model of sleep-disordered breathing, we investigated respiration during wakefulness and sleep in the English bulldog. This breed is characterized by an abnormal upper airway anatomy, with enlargement of the soft palate and narrowing of the oropharynx. During sleep, the animals had disordered respiration and episodes of O2 desaturation. These were worst in rapid-eye-movement (REM) sleep, with most bulldogs having O2 saturations of less than 90% for prolonged durations. In contrast, control dogs never desaturated. In REM sleep, the bulldogs had episodes of both central and obstructive apnea, the latter being associated with paradoxical movements of the rib cage and abdomen. During wakefulness, the bulldogs were hypersomnolent as evidenced by a shortened sleep latency (mean of 12 min compared with greater than 150 min for controls). This animal model should facilitate studies of the natural history of the sleep apnea syndrome and its complications.     

Positive outcome of average volume-assured pressure support mode of a Respironics V60 Ventilator in acute exacerbation of chronic obstructive pulmonary disease: a case report

ABSTRACT: INTRODUCTION: We were able to treat a patient with acute exacerbation of chronic obstructive pulmonary disease who also suffered from sleep-disordered breathing by using the average volume-assured pressure support mode of a Respironics V60 Ventilator (Philips Respironics: United States). This allows a target tidal volume to be set based on automatic changes in inspiratory positive airway pressure. This removed the need to change the noninvasive positive pressure ventilation settings during the day and during sleep. The Respironics V60 Ventilator, in the average volume-assured pressure support mode, was attached to our patient and improved and stabilized his sleep-related hypoventilation by automatically adjusting force to within an acceptable range. CASE PRESENTATION: Our patient was a 74-year-old Japanese man who was hospitalized for treatment due to worsening of dyspnea and hypoxemia. He was diagnosed with acute exacerbation of chronic obstructive pulmonary disease and full-time biphasic positive airway pressure support ventilation was initiated. Our patient was temporarily provided with portable noninvasive positive pressure ventilation at night-time following an improvement in his condition, but his chronic obstructive pulmonary disease again worsened due to the recurrence of a respiratory infection. During the initial exacerbation, his tidal volume was significantly lower during sleep (378.9 +/- 72.9mL) than while awake (446.5 +/- 63.3mL). A ventilator that allows ventilation to be maintained by automatically adjusting the inspiratory force to within an acceptable range was attached in average volume-assured pressure support mode, improving his sleep-related hypoventilation, which is often associated with the use of the Respironics V60 Ventilator. Polysomnography performed while our patient was on noninvasive positive pressure ventilation revealed obstructive sleep apnea syndrome (apnea-hypopnea index = 14), suggesting that his chronic obstructive pulmonary disease was complicated by obstructive sleep apnea syndrome. CONCLUSION: In cases such as this, in which patients with severe acute respiratory failure requiring full-time noninvasive positive pressure ventilation therapy also show sleep-disordered breathing, different ventilator settings must be used for waking and sleeping. On such occasions, the Respironics V60 Ventilator, which is equipped with an average volume-assured pressure support mode, may be useful in improving gas exchange and may achieve good patient compliance, because that mode allows ventilation to be maintained by automatically adjusting the inspiratory force to within an acceptable range whenever ventilation falls below target levels.     

Glottic and cervical tracheal narrowing in patients with obstructive sleep apnea

There are several studies showing that patients with idiopathic obstructive sleep apnea (OSA) have a narrow and collapsible pharynx that may predispose them to repeated upper airway occlusions during sleep. We hypothesized that this structural abnormality may also extend to the glottic and tracheal region. Consequently, we measured pharyngeal (Aph), glottic (Agl), cervical tracheal (Atr1), midtracheal (Atr2), and distal (Atr3) tracheal areas during tidal breathing in 66 patients with OSA (16 nonobese and 50 obese) and 8 nonapneic controls. We found that Aph, Agl, and Atr1, but not Atr2 or Atr3, were significantly smaller in the OSA group than in the control group. Obese patients with OSA had the smallest upper airway area, although the nonapneic controls had the largest areas. Multiple linear regression analysis revealed that the pharyngeal area, cervical tracheal area, and body mass index were all independent determinants of the apnea-hypopnea index, accounting for 31% of the variability in apnea-hypopnea index. Aph, Agl, and Atr showed significant correlation with the body mass index. We conclude that sleep-disordered breathing is associated with diffuse upper airway narrowing and that obesity contributes to this narrowing. Furthermore, we speculate that a common pathophysiological mechanism may be responsible for this reduction in upper airway area extending from the pharynx to the proximal trachea.     

Bradyarrythmias in the obstructive sleep apnea sundrome: a dangerous complication or defense mechanism?

Sleep is characterized by cycling and consecutive alternation of different phases and stages, each of which features intrinsic changes in autonomic regulation with heart rate oscillations; this may cause heart rhythm disorders, especially in the presence of comorbidities. This review addresses the issues of interrelationship between cardiac conduction disorders and obstructive sleep apnea. It is shown that some mechanisms of bradyarrythmia emergence (first of all, features of autonomic regulation with increases in parasympathetic tone) under respiratory arrest during sleep are also inherent to human divers as well as aquatic or para-aquatic mammals that have to hold their breath when diving or staying under water for a long time. These mechanisms may fulfill the defense function.     

Hemodynamic effects of pressures applied to the upper airway during sleep.

The increase in systemic blood pressure after an obstructive apnea is due, in part, to sympathetically mediated vasoconstriction. We questioned whether upper airway (UA) receptors could contribute reflexly to this vasoconstriction. Four unanesthetized dogs were studied during wakefulness and non-rapid-eye-movement (NREM) sleep. The dogs breathed via a fenestrated tracheostomy tube sealed around the tracheal stoma. The snout was sealed with an airtight mask, thereby isolating the UA when the fenestration was closed and exposing the UA to negative inspiratory intrathoracic pressure when it was open. The blood pressure response to three UA perturbations was studied: 1) square-wave negative pressures sufficient to cause UA collapse with the fenestration closed during a mechanical hyperventilation-induced central apnea; 2) tracheal occlusion with the fenestration open vs. closed; and 3) high-frequency pressure oscillations (HFPO) with the fenestration closed. During NREM sleep, 1) blood pressure response to tracheal occlusion was similar with the fenestration open or closed; 2) collapsing the UA with negative pressures failed to alter blood pressure during a central apnea; and 3) application of HFPO to the UA during eupnea and resistive-loaded breaths increased heart rate and blood pressure. However, these changes were likely to be secondary to the effects of HFPO-induced reflex changes on prolonging expiratory time. These findings suggest that activation of UA pressure-sensitive receptors does not contribute directly to the pressor response associated with sleep-disordered breathing events.     

Sleep-related obstructive disordered breathing in cleft palate patients after palatoplasty

Sleep-disordered breathing is frequently associated with children presenting congenital midface defects. Because of structural and functional anomalies in the upper airway, children with cleft palate, especially after surgery, may carry a higher risk of developing sleep-disordered breathing. However, the presence of such sleep-disordered breathing in older cleft palate children has not been emphasized. The aim of this comparative overnight cardiorespiratory sleep study was to evaluate cleft palate patients according to sleep-disordered breathing. A group of 43 cleft palate children (17 girls and 26 boys; mean age, 12.1 +/- 3.8 years) was compared with a control group of 20 randomly selected, noncleft children matched for age, sex, and body mass index. None of the patients suffered from manifest sleep-disordered breathing. Cleft palate patients had a statistically significantly higher respiratory disturbance index and snoring index, but no increased apnea index. The data suggest that cleft palate patients having undergone primary closure of the palate demonstrate microsymptoms of nocturnal upper airway obstruction.     

Nocturia, sleep-disordered breathing, and cardiovascular morbidity in a community-based cohort

Background

Nocturia has been independently associated with cardiovascular morbidity and all-cause mortality, but such studies did not adjust for sleep-disordered breathing (SDB), which may have mediated such a relationship. Our aims were to determine whether an association between nocturia and cardiovascular morbidity exists that is independent of SDB. We also determined whether nocturia is independently associated with SDB.

Methodology/Principal Findings

In order to accomplish these aims we performed a cross-sectional analysis of the Sleep Heart Health Study that contained information regarding SDB, nocturia, and cardiovascular morbidity in a middle-age to elderly community-based population. In 6342 participants (age 63±11 [SD] years, 53% women), after adjusting for known confounders such as age, body mass index, diuretic use, diabetes mellitus, alpha-blocker use, nocturia was independently associated with SDB (measured as Apnea Hypopnea index >15 per hour; OR 1.3; 95%CI, 1.2–1.5). After adjusting for SDB and other known confounders, nocturia was independently associated with prevalent hypertension (OR 1.23; 95%CI 1.08–1.40; P = 0.002), cardiovascular disease (OR 1.26; 95%CI 1.05–1.52; P = 0.02) and stroke (OR 1.62; 95%CI 1.14–2.30; P = 0.007). Moreover, nocturia was also associated with adverse objective alterations of sleep as measured by polysomnography and self-reported excessive daytime sleepiness (P<0.05).

Conclusions/Significance

Nocturia is independently associated with sleep-disordered breathing. After adjusting for SDB, there remained an association between nocturia and cardiovascular morbidity. Such results support screening for SDB in patients with nocturia, but the mechanisms underlying the relationship between nocturia and cardiovascular morbidity requires further study. MeSH terms: Nocturia, sleep-disordered breathing, obstructive sleep apnea, sleep apnea, polysomnography, hypertension.     

Obstructive sleep apnea and chronic intermittent hypoxia: a review

Hypoxia is an important topic both physiologically and clinically. Traditionally, physiology research has been focusing on the effect of acute and chronic sustained hypoxia and human adaptive response to high altitude. In the past 20 years, genetic studies by many have expanded our understanding of hypoxia to the molecular level. However, in contrast to our extensive knowledge about acute and chronic sustained hypoxia, we know relatively little about the effect of chronic intermittent hypoxia (CIH). In recent years, CIH has attracted more research attention because of the increasing prevalence of obesity and obstructive sleep apnea (OSA) in the western countries. Clinically, CIH is commonly seen in patients with sleep-disordered breathing including OSA, Cheyne-Stokes respiration and nocturnal hypoventilation. It was estimated that for OSA of at least mild severity prevalence estimates range from 3 to 28% in the general population. OSA is characterized by recurrent upper airway collapse during sleep leading to intermittent nocturnal hypoxia and sleep fragmentation. OSA is associated with significant mortality and morbidity including neurocognitive dysfunction, hypertension, many cardiovascular disorders and metabolic disorders such as diabetes and metabolic syndrome. The intermittent hypoxia in OSA closely mimics what is seen in the ischemia-reperfusion injury. Experimentally, there is no universally accepted definition for CIH. Laboratory protocols vary greatly in duration of hypoxia exposure, numbers of hypoxia episodes per day and the total number of days of exposure. Despite the lack of a uniform definition, recent data suggest that CIH may lead to multiple long-term pathophysiologic consequences similar to what we see in patients with OSA. Recent evidences also demonstrate that there are remarkable differences in the response of the physiologic systems to sustained hypoxia and intermittent hypoxia. This review is aimed to briefly discuss the clinical significance of sleep-disordered breathing and our current understanding of CIH.     

Compensatory responses to upper airway obstruction in obese apneic men and women

Defective structural and neural upper airway properties both play a pivotal role in the pathogenesis of obstructive sleep apnea. A more favorable structural upper airway property [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] has been documented for women. However, the role of sex-related modulation in compensatory responses to upper airway obstruction (UAO), independent of the passive Pcrit, remains unclear. Obese apneic men and women underwent a standard polysomnography and physiological sleep studies to determine sleep apnea severity, passive Pcrit, and compensatory airflow and respiratory timing responses to prolonged periods of UAO. Sixty-two apneic men and women, pairwise matched by passive Pcrit, exhibited similar sleep apnea disease severity during rapid eye movement (REM) sleep, but women had markedly less severe disease during non-REM (NREM) sleep. By further matching men and women by body mass index and age (n = 24), we found that the lower NREM disease susceptibility in women was associated with an approximately twofold increase in peak inspiratory airflow (P = 0.003) and inspiratory duty cycle (P = 0.017) in response to prolonged periods of UAO and an ～20% lower minute ventilation during baseline unobstructed breathing (ventilatory demand) (P = 0.027). Thus, during UAO, women compared with men had greater upper airway and respiratory timing responses and a lower ventilatory demand that may account for sex differences in sleep-disordered breathing severity during NREM sleep, independent of upper airway structural properties and sleep apnea severity during REM sleep.     

Recent advances in obstructive sleep apnea pathophysiology and treatment

Obstructive sleep apnea (OSA) is a sleep disorder characterized by recurring collapse of the pharyngeal airway leading to restricted airflow. OSA is becoming increasingly common with at least moderate disease now evident in 17% of middle aged men and 9% of women. The list of recognized adverse health consequences associated with OSA is growing and includes daytime symptoms of sleepiness, impaired cognition and risk of motor vehicle accidents as well as associations with hypertension, cardiovascular morbidity, malignancy and all-cause mortality. In this context adequate treatment of OSA is imperative; however, there are well-recognized pitfalls in the uptake and usage of the standard treatment modality, Continuous Positive Airway Pressure (CPAP). A broad range of pathophysiological mechanisms are now recognized beyond an anatomically smaller pharyngeal airway and impaired compensatory pharyngeal muscle responsiveness. Perturbations in ventilatory control stability, low arousal threshold, sleep-related decrease in lung volume and fluid redistribution as well as upper airway surface tension have all been shown to variously contribute to sleep-disordered breathing. Many new therapies are emerging from these advances in understanding of the mechanisms of OSA. Although many may not be universally effective, the promise of phenotyping patients according to their individual pathophysiology in order to target one or more therapies may prove highly effective and allow the treatment of OSA towards a personalized medicine approach.

     

Effects of increase in body temperature on the breathing pattern in premature infants

This study was designed to determine the effects of a mild increase in body temperature within the physiological range (0.8 degrees C) in healthy premature infants. Seven unsedated premature infants (38.4 wk +/- 1.5 postconceptional age) were monitored polygraphically during "morning naps" in an incubator under two different environmental temperatures: (1) normothermia with the incubator temperature set at 25 degrees C and the rectal temperature equal to 36.9 degrees C +/- 0.1; (2) hyperthermia with the incubator temperature set at 35 degrees C and the rectal temperature equal to 37.7 degrees C +/- 0.15. Respiratory frequency and heart rate, respiratory events, i.e., central and obstructive apnea, and periodic breathing with and without apneic oscillations were tabulated. Results for respiratory events were expressed as (1) indices of the total number of respiratory events, and of specific respiratory events per hour of total, quiet and active sleep times; (2) duration of total and specific respiratory events expressed as a percentage of total sleep, quiet and active sleep times. Respiratory frequency and heart rate were significantly increased by hyperthermia (P less than 0.05). Hyperthermia did not significantly modify the indices or the duration of central and obstructive apnea. But the indices and the duration of periodic breathing with and without apneic oscillations were significantly increased by hyperthermia during active sleep (P less than 0.05) but not during quiet sleep. The present study shows that a mild increase in body temperature within the physiological range in premature infants enhances the instability of the breathing pattern during active sleep.     

The positional characteristics of patients with obstructive sleep apnea: a single institute retrospective study in Japan

Sleep and Biological Rhythms - Obstructive sleep apnea (OSA) causes sleep-disordered breathing (SDB) due to upper airway obstruction. The severity of OSA changes with position during sleep....     

Periodicities in respiration and heart rate in newborns

Periodic breathing is common in normal infants, but may be associated with prolonged apnea leading to crib death. The mechanisms of periodic breathing and its relation to normal breathing patterns are unclear. We recorded respiratory and heart rate (HR) patterns of 11 healthy newborn infants during quiet sleep, in both normal and periodic breathing. Spectral analysis of the respiratory pattern revealed a low-frequency (LF) periodicity in normal breathing approximately equal to the frequency of periodic breathing when this occurs. Periodic breathing thus appears to be an exaggeration of an underlying slow amplitude variation which is present in regular breathing. LF periodicity also appeared in the HR pattern in both normal and periodic breathing, suggesting an LF modulation of cardiovascular control as well. The lack of a definite phase relation between HR and ventilation at LF may indicate dominant peripheral, rather than central, interactions between HR and respiration at these frequencies.