Intermittent Hypoxemia Research Articles

Caffeine therapy in preterm infants.

Caffeine is the most commonly used medication for treatment of apnea of prematurity. Its effect has been well established in reducing the frequency of apnea, intermittent hypoxemia, and extubation failure in mechanically ventilated preterm infants. Evidence for additional short-term benefits on reducing the incidence of bronchopulmonary dysplasia and patent ductus arteriosus has also been suggested. Controversies exist among various neonatal intensive care units in terms of drug efficacy compared to other methylxanthines, dosage regimen, time of initiation, duration of therapy, drug safety and value of therapeutic drug monitoring. In the current review, we will summarize the available evidence for the best practice in using caffeine therapy in preterm infants.

Implications of Renal Denervation Therapy in Patients with Sleep Apnea.

Obstructive sleep apnea (OSA) syndrome is a prevalent condition characterized by repeated episodes of obstruction of the upper airway, leading to intermittent hypoxemia and important endothelial and anatomical dysfunctions that cause cardiovascular and cerebrovascular disease. The finding of the relationship between OSA and hypertension, especially resistant hypertension (RHT), has increased the interest in therapeutic strategies that affect renal sympathetic activity in these patients. The observational studies published until now demonstrated that renal denervation therapy can reduce the severity of OSA syndrome. Renal sympathetic denervation (RDN) could be a future therapeutic possibility for conditions other than RHT, such as atrial fibrillation, heart failure, obesity, and OSA syndrome, where renal sympathetic system plays an important physiological role. The aim of this review was to elucidate the implications of renal sympathetic activity in OSA syndrome.

Epidemiology and Etiology of Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is one of common sleep disorders in western countries, affecting 4% of males and 2% of females. It is characterized by repeated obstruction of the upper airway during sleep, leading to intermittent hypoxemia, sympathetic activation, and sleep fragmentation. OSA is an independent risk factor for a range of medical problems, including cardiovascular disease, diabetes, depression, and cognitive dysfunctions. The etiology of OSA is complex and incompletely understood, but recent studies have shown that the development of OSA depends on the structure of the airway anatomy, the responsiveness of the upper airway dilator muscle to stimulation, and the stability of the respiratory control system. This review details the epidemiological and experimental evidence surrounding the associations between OSA and chronic diseases. Recent findings on the etiology of OSA will also be discussed. (Korean J Med 2015;89:6-12)

Cerebral Oxygenation during Intermittent Hypoxemia and Bradycardia in Preterm Infants

Background: Episodes of hypoxemia and bradycardia frequently occur with apnea of prematurity in preterm infants. Little is known about the impact of different event types on the brain. Objectives: To describe the influence of hypoxemia and bradycardia, either isolated or in combination, on cerebral oxygenation. Methods: In 16 preterm infants with intermittent hypoxemia and/or bradycardia, cerebral tissue oxygen saturation (StO₂, as measured by near-infrared spectroscopy), heart rate and pulse oximetric saturation (SpO₂) were recorded simultaneously for 16 h. Events were classified as isolated bradycardia (type 1), isolated hypoxemia (type 2) or combined (simultaneous, type 3; bradycardia first, type 4; hypoxemia first, type 5). Primary outcome was a score representing the area below baseline for cerebral StO₂ desaturation during an event. Secondary outcomes were duration and depth of cerebral desaturation. Results: Patients had a median (range) gestational age of 25.9 (22.6-30.4) weeks and a postnatal age of 32.5 (7-58) days. The median (quartiles) number of events was 49 (34-58). Isolated hypoxemias were the most frequent events (24; 9-36) and isolated bradycardias the least common (0; 0-1). Cerebral StO₂ baseline was not different between event types. Cerebral desaturation score, duration of event and depth of cerebral desaturation were smallest for isolated bradycardias and largest for combined events, especially for those starting with hypoxemia followed by bradycardia. Regardless of event type, 12/16 infants maintained cerebral StO₂ >60% despite severe SpO₂ desaturations. Conclusions: Isolated bradycardias had the lowest impact on cerebral desaturation, and combined events had the highest. Most infants preserved cerebral oxygenation >60% during events.

Mild intermittent hypoxemia in neonatal mice causes permanent neurofunctional deficit and white matter hypomyelination

Very Low Birth Weight (VLBW) premature infants experience numerous, often self-limited non-bradycardic episodes of intermittent hypoxemia (IH). We hypothesized that these episodes of IH affect postnatal white matter (WM) development causing hypomyelination and neurological handicap in the absence of cellular degeneration. Based on clinical data from ten VLBW neonates; a severity, daily duration and frequency of non-bradycardic IH episodes were reproduced in neonatal mice. Changes in heart rate and cerebral blood flow during IH were recorded. A short-term and long-term neurofunctional performance, cerebral content of myelin basic protein (MBP), 2′3′ cyclic-nucleotide 3-phosphodiesterase (CNPase), electron microscopy of axonal myelination and the extent of cellular degeneration were examined.Neonatal mice exposed to IH exhibited no signs of cellular degeneration, yet demonstrated significantly poorer olfactory discrimination, wire holding, beam and bridge crossing, and walking-initiation tests performance compared to controls. In adulthood, IH-mice demonstrated no alteration in navigational memory. However, sensorimotor performance on rota-rod, wire-holding and beam tests was significantly worse compared to naive littermates. Both short- and long-term neurofunctional deficits were coupled with decreased MBP, CNPase content and poorer axonal myelination compared to controls.In neonatal mice mild, non-ischemic IH stress, mimicking that in VLBW preterm infants, replicates a key phenotype of non-cystic WM injury: permanent hypomyelination and sensorimotor deficits. Because this phenotype has developed in the absence of cellular degeneration, our data suggest that cellular mechanisms of WM injury induced by mild IH differ from that of cystic periventricular leukomalacia where the loss of myelin-producing cells and axons is the major mechanism of injury.

Nocturnal stem cell mobilization in patients with obstructive sleep apnoea: a pilot study.

Patients with obstructive sleep apnoea (OSA) experience repetitive cessation of breathing during sleep, leading to intermittent hypoxaemia, excessive oxidative stress and systemic inflammation. These insults may damage the vasculature and provoke the corresponding repair response, such as stem cell mobilization to peripheral blood. This study aimed to investigate nocturnal mobilization of stem cells in OSA. Thirty-five patients with OSA and thirteen healthy controls were enrolled. Polysomnography was performed, and severity of OSA was defined by apnoea-hypopnoea index (AHI). Peripheral venous blood was drawn after and before sleep for measurement of CD34+ cell and SDF-1α level. Stem cell mobilization was gauged by ratios of the CD34+ level in the morning to that at night or by their difference. Correlation analysis was performed to identify factors related to stem cell mobilization. Compared to controls, the nocturnal ratios and difference of CD34+ cell levels were larger in patients with OSA (ratios: 1·141 vs. 0·896, P=0·036; difference: 340 vs. -166/cc blood, P=0·036), suggestive of stem cell mobilization. The mobilization ratios were related to AHI, body mass index (BMI), SpO2 nadir, oxygen desaturation index and time sustaining hypoxaemia. After adjusting age, gender and BMI, AHI (r=0·357, P=0·016) and hypoxaemia-related parameter remained significant. Paired nocturnal differences in CD34+ cell count (P=0·009) and SDF-1α (P=0·001) were also significant in patients with OSA, but not in controls. After CPAP therapy for 6months, the elevated mobilization ratios in patients with OSA tended to decline (P=0·059). CD34+ stem cell mobilization during sleep was observed in OSA.

Bladder Oxidative Stress in Sleep Apnea Contributes to Detrusor Instability and Nocturia

Obstructive sleep apnea is associated with voiding symptoms in humans and animals, and yet its effects on the urinary tract are poorly understood. We examined bladder structure and function, markers of oxidative damage and the redox survival pathway in a rat model of obstructive sleep apnea to identify changes. To model obstructive sleep apnea we used a rat oxycycler system to create cyclical interruption in breathing oxygen, thereby producing intermittent hypoxemia. Male Sprague Dawley® rats were divided into an obstructive sleep apnea, a sham treated and a control group of 8 each. After 8-week exposure to obstructive sleep apnea conditions we assessed daytime and nighttime rat voiding behavior in metabolic cages. Cystometrograms were done and bladder tissue was processed for biochemical assays, enzyme-linked immunosorbent assay and transmission electron microscopy. Increased urinary frequency and total urine output developed in rats exposed to obstructive sleep apnea conditions. Cystometric changes included detrusor instability, bladder noncompliance and increased spontaneous contractions. These changes were associated with bladder oxidative stress characterized by significant increases in tissue levels of malondialdehyde and advanced oxidation protein products. Obstructive sleep apnea activated cell survival signaling manifested by increased expression of PI3K and phosphorylated Akt1. Transmission electron microscopy revealed marked ultrastructural damage to subcellular elements. Intermittent hypoxia in obstructive sleep apnea causes oxidative stress with ultrastructural and functional changes in the bladder. Sleep apnea related nocturia/voiding symptoms could be the result of these direct changes. Untreated sleep apnea has significant health consequences. Identifying urinary oxidative stress products in patients with nocturia may be useful as an economical noninvasive biomarker to identify undiagnosed obstructive sleep apnea.

P293 Is Obstructive Sleep Apnoea A Risk Factor For Chronic Kidney Disease?

Background Obstructive sleep apnoea (OSA) is associated with intermittent hypoxaemia which leads to activation of a number of pathways including oxidative stress, sympathetic nervous system, endothelial dysfunction and inflammation. These in turn lead to hypertension and atherosclerosis. There is some evidence that the same process may predispose to renal dysfunction. In this retrospective study, we compared a group people with hypertension and OSA on continuous positive airways pressure therapy (CPAP) with matched control group not known to have OSA. Method Patients with known OSA and controls matched for age, sex and BMI were selected retrospectively from a hypertension clinic database. The two groups were compared using the following parameters: mean 24-hour systolic blood pressure (SBP, mmHg), mean serum creatinine (micromol/l) and mean urine albumin/creatinine ratio (ACR. mg/mmol). Results Forty-nine patients were identified with confirmed OSA on CPAP. 6 were excluded due to insufficient data. Of the 43 remaining patients 35 were male, the mean age was 53.5 years and the mean BMI was 34.6 km/m2. The mean SBP was 143 in patients versus 135 in controls (p = 0.04). The mean serum creatinine was 94.0 in patients versus 93.4 in controls (p = 0.45). The mean ACR was 2.50 in patients versus 0.63 in controls (p = 0.031). Conclusion This retrospective case-control study shows a higher prevalence of hypertension and proteinuria in patients with treated OSA when compared with controls matched for age, sex and BMI. OSA in the patients may not have been adequately treated. There may have been undiagnosed OSA in the controls. Patients’ higher proteinuria may have been caused by their more severe hypertension. Causation is not proven. However this study raises the possibility that OSA might predispose to chronic kidney disease. A larger, prospective study might confirm this finding and provide information on causation.

Obstructive sleep apnoea, insulin resistance and adipocytokines.

Obstructive sleep apnoea (OSA) is associated with multiple cardiometabolic abnormalities. Obesity is considered a major risk factor for the development of OSA, and it is also an established risk factor for insulin resistance and other cardiometabolic disorders. The enigma remains whether OSA has any causal role in the adverse metabolic profile, independent of or beyond that due to obesity. Sleep apnoeas and hypopnoeas result directly in intermittent hypoxaemia and cerebral arousals, both of which may evoke a cascade of downstream biologic responses in various body tissues and cells. Adipose tissue is a major source of adipocytokines many of which play important roles in the regulation of various metabolic functions. It is hypothesized that OSA may, through its unique pathophysiology, affect metabolic function through modulation of production or action of adipocytokines. This review focuses on insulin resistance, glucose metabolism and relevant adipocytokines in the context of OSA.

Sleep-related intermittent hypoxemia and glucose intolerance: a community-based study

BackgroundIntermittent hypoxemia is a fundamental pathophysiological consequence of sleep-disordered breathing and may alter glucose metabolism. To characterize the association between sleep-related intermittent hypoxemia and glucose metabolism, overnight pulse-oximetry and an oral glucose tolerance test were completed in a cohort of middle-aged and older Japanese adults. MethodsThe study sample consisted of 1836 community-dwelling Japanese (age, 30–79 years; women, 65.5%; mean body mass index, 23.1 kg/m2). The oxygen desaturation index (ODI) was quantified during sleep using a ≥3% oxygen desaturation threshold and categorized as normal (<5.0 events/h), mild (5.0–15.0 events/h), and moderate to severe (≥15.0 events/h). The independent associations between the ODI and the prevalence of impaired fasting glucose, impaired glucose tolerance, diabetes, and two metrics of insulin resistance [homeostasis model assessment index for insulin resistance (HOMA-IR) and Matsuda index] were examined. ResultsCompared with subjects with an ODI < 5 events/h, the adjusted odds ratio for prevalent impaired fasting glucose, glucose intolerance, and diabetes for subjects with an ODI ≥15.0 events/h were 1.27 (95% confidence interval, 0.72–2.23), 1.69 (1.03–2.76), and 1.28 (0.59–2.79), respectively. Both HOMA-IR and Matsuda index were significantly associated with the severity of sleep-related intermittent hypoxemia as assessed by the ODI (P for trend = 0.03 and 0.007, respectively). ConclusionAmong middle-aged and older Japanese adults, sleep-related intermittent hypoxemia is associated with glucose intolerance and insulin resistance, and may contribute to the development of type 2 diabetes mellitus.

The effect of red blood cell transfusion on intermittent hypoxemia in ELBW infants.

ObjectiveTo test the hypothesis that the effect of red blood cell (RBC) transfusion on intermittent hypoxemia (IH) in extremely low birth weight (ELBW) infants is dependent on postnatal age.Study DesignOxygen saturation of 130 ELBW infants, who required transfusion, was monitored continuously for the first 8wks of life. We compared the characteristics of IH (SpO2 ≤ 80% for ≥4s and ≤3min), 24h before and both 24h and 24-48h after each RBC transfusion at three distinct time periods: Epoch 1, 1-7d; Epoch 2, 8-28d; and Epoch 3, >28d.ResultsIn Epoch 1, the frequency and severity of IH events were not significantly different before and after transfusion. In both Epochs 2 and 3 there was a decrease in IH frequency and severity 24h after RBC transfusion that persisted for 48h. In addition, there was a decrease in the overall time spent with SpO2 ≤ 80% which persisted for 24h after transfusion in Epochs 1 and 3, and for 48h in Epoch 3.ConclusionThe benefit of RBC transfusion on IH is age dependent as improvement in the frequency and severity of IH after transfusion only occurs beyond the first week of life. These observations will aid clinician’s decision making by clarifying the benefit of RBC transfusions on patterns of oxygenation in preterm infants.

Pathophysiology of human ventilatory control.

We review the substantial recent progress made in understanding the underlying mechanisms controlling breathing and the applicability of these findings to selected human diseases. Emphasis is placed on the sites of central respiratory rhythm and pattern generation as well as newly described functions of the carotid chemoreceptors, the integrative nature of the central chemoreceptors, and the interaction between peripheral and central chemoreception. Recent findings that support critical contributions from cortical central command and muscle afferent feedback to exercise hyperpnoea are also reviewed. These basic principles, and the evidence supporting chemoreceptor and ventilatory control system plasticity during and following constant and intermittent hypoxaemia and stagnant hypoxia, are applied to: 1) the pathogenesis, consequences and treatment of obstructive sleep apnoea; and 2) exercise hyperpnoea and its control and limitations with ageing, chronic obstructive pulmonary disease and congestive heart failure.

CPAP versus Oxygen in Obstructive Sleep Apnea

BackgroundObstructive sleep apnea is associated with hypertension, inflammation, and increased cardiovascular risk. Continuous positive airway pressure (CPAP) reduces blood pressure, but adherence is often suboptimal, and the benefit beyond management of conventional risk factors is uncertain. Since intermittent hypoxemia may underlie cardiovascular sequelae of sleep apnea, we evaluated the effects of nocturnal supplemental oxygen and CPAP on markers of cardiovascular risk.MethodsWe conducted a randomized, controlled trial in which patients with cardiovascular disease or multiple cardiovascular risk factors were recruited from cardiology practices. Patients were screened for obstructive sleep apnea with the use of the Berlin questionnaire, and home sleep testing was used to establish the diagnosis. Participants with an apnea–hypopnea index of 15 to 50 events per hour were randomly assigned to receive education on sleep hygiene and healthy lifestyle alone (the control group) or, in addition to education, either CPAP or nocturnal supplemental oxygen. Cardiovascular risk was assessed at baseline and after 12 weeks of the study treatment. The primary outcome was 24-hour mean arterial pressure.ResultsOf 318 patients who underwent randomization, 281 (88%) could be evaluated for ambulatory blood pressure at both baseline and follow-up. On average, the 24-hour mean arterial pressure at 12 weeks was lower in the group receiving CPAP than in the control group (−2.4 mm Hg; 95% confidence interval [CI], −4.7 to −0.1; P=0.04) or the group receiving supplemental oxygen (−2.8 mm Hg; 95% CI, −5.1 to −0.5; P=0.02). There was no significant difference in the 24-hour mean arterial pressure between the control group and the group receiving oxygen. A sensitivity analysis performed with the use of multiple imputation approaches to assess the effect of missing data did not change the results of the primary analysis.ConclusionsIn patients with cardiovascular disease or multiple cardiovascular risk factors, the treatment of obstructive sleep apnea with CPAP, but not nocturnal supplemental oxygen, resulted in a significant reduction in blood pressure. (Funded by the National Heart, Lung, and Blood Institute and others; HeartBEAT ClinicalTrials.gov number, NCT01086800.)

Usefulness of reinforcing interventions on continuous positive airway pressure compliance.

BackgroundObstructive sleep apnea (OSA) is a high prevalence sleep disorder characterized by upper airway obstruction during sleep, nocturnal intermittent hypoxemia, poor sleep quality, risk for cardiovascular and metabolic diseases. The adherence to CPAP is the key for an effective management of these patients.The aim of the study was to assess the adherence to CPAP therapy with and without early reinforcing interventions, consisting of motivational reinforcement and technical support in the first month of therapy.MethodsForty patients with OSA undergoing counseling and a one year follow-up on a quarterly basis were included in the study. Twenty subjects (intervention group) underwent reinforcing interventions with telephone interviews in the first month of therapy, and twenty (control group) remained without reinforcing interventions. The two populations were homogeneous for age, severity of illness and BMI.ResultsDuring the first month, intervention group patients showed a higher number of nights with a device use ≥4 hours. Average treatment adherence in the first month (days of therapy with at least 4 hours per night on the total number of days from device delivery) was 77.5% in the intervention group and 55.7% in the control group (p = 0.022). At one year the differences between the two groups were not significant.ConclusionsOur findings suggest that it is important that adequate time and effort is spent to ensure patient comfort at the time of CPAP therapy start to optimize acceptance and adherence to treatment, and suggest that it is necessary to maintain reinforcing interventions over time.

Diabetes, sleep and metformin.

Cover image: ‘African Tears’ by Rebekka Ivacson. © All rights reserved David Hadden sadly died on 26 February 2014. He was an ‘old school’ diabetologist and an internationally respected authority on diabetes and pregnancy. Over the last 4 years he served as technical editor for Diabetic Medicine and despite his illness worked to the end of 2013. He will be truly missed by all those that contribute to Diabetic Medicine. At the European Association for the Study of Diabetes (EASD) 2013 board meeting when he announced his impending retirement from the journal he said that he would be known by the journal for the person who removed abbreviations; we celebrate his life and legacy to people with diabetes. It is well established that there is a relationship between sleep disturbances and insulin resistance 1, with a wealth of evidence to support that sleep disturbances results in decreased insulin sensitivity through the effects of intermittent hypoxaemia and sleep fragmentation. There is some evidence to suggest bidirectionality with hyperinsulinaemia and insulin resistance once established, promoting sleep disturbances arising from diabetic neuropathy and/or ventilatory instability. As metformin exerts its effect on insulin resistance, one might therefore postulate that it could have a beneficial effect on sleep disturbance. This month's highlighted article in this issue of Diabetic Medicine is by Kajbaf and colleagues (page 577). In their short report they describe a relationship between metformin therapy and sleep quantity and quality in patients with Type 2 diabetes. The research is based on a retrospective study of 387 consecutive outpatient referrals with Type 2 diabetes for screening for sleep apnoea syndrome at Amiens University Hospital (France). Two groups were compared; 314 subjects who were metformin treated and 73 subjects who did not take metformin. In the metformin-treated group, total sleep time was longer by 36 min and sleep efficiency was also higher. Importantly, these differences persisted in a multivariate analysis despite a higher BMI in the metformin-treated group. Although the number of insulin-treated patients were similar in both groups (15–17%), more patients not taking metformin were on sulphonylurea therapy (55%) compared with those who were metformin treated (28%). As pointed out by the authors, there are a number of weaknesses of the study, including study design, the low number of people with Type 2 diabetes not being treated with metformin and differences in the number of concomitant anti-diabetic medications. Nonetheless, the data presented require the randomized clinical trial evidence of the benefit of metformin on sleep disturbance in Type 2 diabetes.

Le syndrome d’apnées obstructives du sommeil : une cause de troubles cognitifs chez les personnes âgées ?

Obstructive sleep apnea syndrome is a chronic disease characterized by repeated upper airway obstructions during sleep, resulting in fragmented sleep with arousals, nocturnal intermittent hypoxemia and diurnal dysfunctions. Despite its high prevalence in elderly, sleep apnea syndrome seems to be underestimated and difficult to be recognized because of the lack of clinical symptoms specificity in this population. Among the numerous consequences of the obstructive sleep apnea syndrome, cognitive impairment prevails on the attention, executive functions and memory. Neuroimaging studies in human and experimental models allowed to highlight neural correlates of these cognitive dysfunctions in obstructive sleep apnea syndrome. The obstructive sleep apnea syndrome with cognitive impairment shares some features with Alzheimer's disease, involving genetic predisposition ApoE4, hippocampus and synaptic plasticity abnormalities. In this context, the question arises whether obstructive sleep apnea syndrome is a possible etiological or aggravating factor of cognitive decline in elderly with mild cognitive impairment or Alzheimer's disease. Although there are conflicting results in studies evaluating therapeutic efficiency of continuous positive air pressure, obstructive sleep apnea syndrome seems nevertheless as a correctable factor, at least for its impact on some cognitive consequences. Looking for sleep apnea syndrome in elderly with cognitive decline should be considered in a global, diagnosis and therapeutic management.

Is sleep-disordered breathing associated with miscarriages? An emerging hypothesis

Sleep-disordered breathing (SDB) is a common disorder that has numerous medical consequences including cardiovascular morbidity. The clinical presentation in women is frequently vague, leading to its under-recognition in this population. Sleep is known to influence several female hormonal cycles including estrogen, progesterone, prolactin, luteinizing hormone (LH), and follicle stimulating hormone (FSH); consequently, sleep disruption may have adverse effects on female health including pregnancy. Miscarriage, defined as the loss of a pregnancy in the first trimester, occurs in one in four pregnancies; in up to half of cases, the cause may be unknown. Risk factors for miscarriage include increased age, increased weight, and a history of polycystic ovarian syndrome, all of which are also risk factors for SDB. Since SDB is frequently accompanied by sleep fragmentation and intermittent hypoxemia, we speculate that these factors may contribute to miscarriage risk. If this is the case, then treatment of SDB may be a possible intervention for subsequent pregnancies.

Role of chemoreception in cardiorespiratory acclimatization to, and deacclimatization from, hypoxia

During sojourn to high altitudes, progressive time-dependent increases occur in ventilation and in sympathetic nerve activity over several days, and these increases persist upon acute restoration of normoxia. We discuss evidence concerning potential mediators of these changes, including the following: 1) correction of alkalinity in cerebrospinal fluid; 2) increased sensitivity of carotid chemoreceptors; and 3) augmented translation of carotid chemoreceptor input (at the level of the central nervous system) into increased respiratory motor output via sensitization of hypoxic sensitive neurons in the central nervous system and/or an interdependence of central chemoreceptor responsiveness on peripheral chemoreceptor sensory input. The pros and cons of chemoreceptor sensitization and cardiorespiratory acclimatization to hypoxia and intermittent hypoxemia are also discussed in terms of their influences on arterial oxygenation, the work of breathing, sympathoexcitation, systemic blood pressure, and exercise performance. We propose that these adaptive processes may have negative implications for the cardiovascular health of patients with sleep apnea and perhaps even for athletes undergoing regimens of "sleep high-train low"!

Proton magnetic resonance spectroscopy of brain in obstructive sleep apnea in Egyptian subjects

ObjectiveThe overall objective of this work is to study the cerebral metabolic changes in patients with OSA and to determine the usefulness of MRS as an objective method for evaluation of CNS impairment in these patients. Materials and methodsThis study included two groups; group1 fifteen (15) patients diagnosed with obstructive sleep apnea hypopnea syndrome, and group 2 ten (10) healthy volunteers of comparable age.Magnetic resonance spectra were obtained from frontal periventricular white matter.For all subjects, height, body weight, and BMI were assessed. Waist and hip circumference were measured and waist/hip ratio (W/H ratio) was calculated.Overnight polysomnography (PSG) to identify sleep apnea was done. Daytime sleepiness was evaluated by the Epworth Sleepiness Scale. Symptoms of anxiety and depression were measured with the Hospital Anxiety and Depression Scale (HADS). ResultsN-acetylaspartate-to-creatine (NAA/Cr) and choline-to-creatine (Cho/Cr) ratios were significantly lower in the frontal white matter of obstructive sleep apnea patients when compared to controls. Absolute concentrations of N-acetylaspartate (NAA) and choline (Cho) were also significantly reduced in the frontal white matter of patients with sleep apnea. Statistically significant negative correlations existed between AHI and metabolites concentrations and ratios in patients with OSAHS. Significant positive correlations existed in patients with OSAHS between Hospital and depression scale for depression (HAD-D) and AHI (r=0.764, p=0.001), ODI (r=0.571, p=0.026), and ESS (r=0.644, p=0.010), respectively. Significant positive correlations existed in patients with OSAHS between Hospital and depression scale for anxiety (HAD-A) and AHI (r=0.753, p=0.001), and ESS (r=0.537, p=0.039), respectively. Multivariate Linear regression model of factors predictive showed AHI as the main predictor factor for choline to creatine ratio in patients with OSAHS with t=5.180, at p<0.001. ConclusionOSA patients show abnormal brain metabolites related to neuronal damage due to intermittent chronic hypoxemia. Anxious and depressive symptoms are highly prevalent in patients with severe untreated OSAS. The severity of depressive and anxious symptoms may be related to excessive daytime sleepiness and to nocturnal hypoxemia both of which are strongly correlated to brain metabolites. AHI seems to be the main predictor factor for choline to creatine ratio in patients with OSAHS.

Hypertension and endothelial dysfunction in obstructive sleep apnea (OSA) – Is it related to hypoxia?

Introduction OSA is a prevalent disorder causing hypertension. Endothelial dysfunction appears to underlie development of hypertension. It is generally believed that intermittent hypoxemia during sleep is the underlying process leading to hypertension. However, patients with OSA and hypertension have increased sympathetic tone while awake so as patients with OSA without hypertension. We have previously shown that both hypertensive (H-OSA) and normotensive OSA (N-OSA) patients have elevated plasma levels of catecholamines. It is not established whether hypoxia during sleep is necessarily the prerequisite process for endothelial dysfunction and hypertension in OSA. We therefore examined the relationship between endothelial-dependent vasodilatory capacity (using brachial artery flow-mediated method, FMD), arterial oxygen saturation (SaO2) in OSA and non-OSA patients with and without hypertension. We also investigated the role of angiogenic inhibitors that are known to cause endothelial dysfunction and hypertension. Materials and methods We studies 95 subjects with and without OSA and hypertension. Plasma angiogenic inhibitors, endoglin (sEng) and fms-like tyrosine kinase-1 (sFlt-1), were measured using ELISA. Results The apnea–hypopnea indexes were 41 ± 5 and 48 ± 4 /h in N-OSA ( n = 27) and H-OSA ( n = 36), respectively, indicating severe OSA. Asleep SaO2 T ± 8 and 40 ± 9 min, respectively. FMD was markedly impaired in H-OSA (8.0% ± 0.5) compared to N-OSA (13.5% ± 0.5, P ± 0.8, P n = 13), and N-non-OSA (16.1% ± 1.0, P n = 19). There was no correlation between T ± 5.9 and 63.9 ± 4.7 pg/ml) compared to N-non-OSA (32.1 ± 6.5, P = 0.0008 and P = 0.0004, respectively) and H-non-OSA (41.2 ± 7.0, P P = 0.03, respectively). sEng was elevated in H-OSA (4.20 ± 0.17 ng/ml) compared with N-OSA (3.64 ± 0.14, P = 0.01) and N-non-OSA (3.48 ± 0.20, P = 0.01). There was a modest but statistically significant inverse correlation between sEng and FMD in only H-OSA group ( r = −0.38, P Conclusion These data show that patients with OSA and hypertension have marked impairment of FMD independent of hypoxia exposure. FMD is not uniformly affected by exposure to intermittent hypoxia or apnea in patient with OSA. Impaired FMD is associated with increased sFlt-1 and sEng. The differences in sEng concentrations between H-OSA and control groups are comparable to those with target organ damage and hypertension and high risk for cardiovascular adverse outcome.