Obstructive Sleep Apnea Hypoxia Research Articles

Time delays between physiological signals in interpreting the body’s responses to intermittent hypoxia in obstructive sleep apnea

Objective. Intermittent hypoxia, the primary pathology of obstructive sleep apnea (OSA), causes cardiovascular responses resulting in changes in hemodynamic parameters such as stroke volume (SV), blood pressure (BP), and heart rate (HR). However, previous studies have produced very different conclusions, such as suggesting that SV increases or decreases during apnea. A key reason for drawing contrary conclusions from similar measurements may be due to ignoring the time delay in acquiring response signals. By analyzing the signals collected during hypoxia, we aim to establish criteria for determining the delay time between the onset of apnea and the onset of physiological parameter response. Approach. We monitored oxygen saturation (SpO2), transcutaneous oxygen pressure (TcPO2), and hemodynamic parameters SV, HR, and BP, during sleep in 66 patients with different OSA severity to observe body’s response to hypoxia and determine the delay time of above parameters. Data were analyzed using the Kruskal–Wallis test, Quade test, and Spearman test. Main results. We found that simultaneous acquisition of various parameters inevitably involved varying degrees of response delay (7.12–25.60 s). The delay time of hemodynamic parameters was significantly shorter than that of SpO2 and TcPO2 (p< 0.01). OSA severity affected the response delay of SpO2, TcPO2, SV, mean BP, and HR (p < 0.05). SV delay time was negatively correlated with the apnea-hypopnea index (r = −0.4831, p< 0.0001). Significance. The real body response should be determined after removing the effect of delay time, which is the key to solve the problem of drawing contradictory conclusions from similar studies. The methods and important findings presented in this study provide key information for revealing the true response of the cardiovascular system during hypoxia, indicating the importance of proper signal analysis for correctly interpreting the cardiovascular hemodynamic response phenomena and exploring their physiological and pathophysiological mechanisms.

0468 Effects of apnea-induced SWS disruption with and without supplemental oxygen on overnight spatial memory in CPAP-treated OSA

Abstract Introduction Sleep disturbance from obstructive sleep apnea (OSA) impairs overnight memory processing. This may be mediated by changes to slow wave sleep (SWS) as less slow wave activity (SWA) is associated with worse overnight spatial and declarative memory. We developed a within-subjects model of SWS-specific CPAP-withdrawal to create 3 polysomnologically (PSG)-verified conditions of 1) stable-SWS on CPAP, 2) SWS-fragmentation with intermittent hypoxemia (OSAsws), and 3) SWS-fragmentation with reduced hypoxemia (OSAsws+O2). Using these conditions, we sought to dissociate of effects of SWS disruption and intermittent hypoxemia on overnight spatial navigational memory. Methods We included 33 patients (7 female, average age 54yrs) with moderate-to-severe OSA (AHI4%&amp;gt;20/hr) who were CPAP-treatment adherent. During each PSG visit, they explored one of three 3D maze environments, performing 3 timed trials before and after each of 3 randomized and counterbalanced SWS disruption conditions [1)CPAP, 2)OSASWS &amp; 3)OSASWS+O2]. %SWS, OSA severity during SWS, frontal SWA(0.5-4 Hz), and overnight change in maze completion times were compared according to PSG condition using Friedman Rank Sum and Conover’s tests. The relationship between SWA and maze performance was tested using Pearson correlation coefficient. Results %SWS was significantly greater during CPAP compared to CPAP-withdrawal conditions (CPAP=17.2%, OSAsws=13.3%, OSAsws+O2=13.8%, p&amp;lt; 0.02). Apnea hypopnea index (AHI3A) in SWS during CPAP-withdrawal was significantly greater compared to CPAP (CPAP=0/hr, OSAsws=24.4/hr, OSAsws+O2=19.3/hr, p&amp;lt; 0.00001). Hypoxic burden in SWS was significantly reduced in the OSAsws+O2 condition vs OSAsws (23 %min/hr vs 37 %min/hr, p &amp;lt; 0.001). No significant differences were observed between the three conditions for SWA or overnight change in maze completion times. When including all PSG visits, greater SWA was significantly associated with better overnight maze improvements (R=0.28,p&amp;lt; 0.01) which approached significance for the CPAP condition in isolation (R=0.33,p=0.068). Conclusion SWS-specific CPAP-withdrawal resulted in recurrence of mild OSA in SWS; supplemental oxygen reduced the hypoxic burden, but SWA did not differ between OSA with hypoxemia and without. There was, however, an overall positive relationship between SWA and maze performance. These observations suggest that the effect on spatial navigation of hypoxia in OSA is mediated by disruption of SWA. Support (if any) R01AG056682, AASM Focused Project Award.

0576 Impact of Obstructive Sleep Apnea on In-Hospital Mortality Due to Acute Myocardial Infarction - A Large Retrospective National Study of Veterans

Abstract Introduction Ischemic preconditioning (IPC) is a phenomenon that refers to multiple, brief periods of myocardial ischemia followed by reperfusion. This counterintuitive preconditioning is thought to provide cardioprotection from subsequent prolonged ischemic events. Obstructive sleep apnea (OSA) may lead to IPC by frequent, recurrent short episodes of hypoxia and sympathetic stimulation. We hypothesized in patients who were admitted with acute myocardial infarction (MI), the presence of OSA was associated with improved survival during the hospitalization, likely due to IPC. Methods This is a retrospective cohort study utilizing national Veterans Health Administration (VHA) records. The cohort includes patients from 1999-2020 with a hospitalization for MI as the principal diagnosis. We confirm the OSA diagnosis using ICD9/10 codes. The primary outcome was in-hospital mortality during the index admission for acute MI. We reported the odds ratio (OR) of in-hospital mortality between with-OSA and without-OSA using logistic regression. We adjusted the OR (aOR) by age, gender, race, ethnicity, BMI, and Charlson Comorbidity index. Results Out of 4,237,444 veterans with any sleep diagnosis, 76,359 patients were hospitalized with a diagnosis of MI. We observed 30,116 with OSA (age, 64±10; BMI, 33±7) and 43,480 without OSA (age, 68±12; BMI, 29±6). The aOR of in-patient mortality was lower in with-OSA (n = 333[1.1%]; aOR, 1.86; 95% CI, 1.63 to 2.12) compared to without-OSA (n = 1,102[2.5%]; aOR, 2.02; 95% CI, 1.78 to 2.30). After stratifying the patients based on previous history of MI, the results remained the same. Conclusion We found that in patients admitted with acute MI, the OSA cohort was associated with lower mortality when compared to non-OSA cohort. We speculate that these differences may be attributed to IPC likely due to repetitive, chronic episodes of hypoxia in obstructive sleep apnea. Further research is warranted to elicit the clinical implications of ischemic preconditioning and OSA. Support (If Any) Culebras, A. Exploring the trail between cerebral ischemic aggravation and ischemic preconditioning. Obstructive sleep apnea leads the way. Sleep Medicine, Volume 67 ,2020, p 276-277Salman LA, Shulman R, Cohen JB. Obstructive sleep apnea, hypertension, and cardiovascular risk: epidemiology, pathophysiology, and management. Curr Cardiol Rep 2020;22(2):6

Impact of obstructive sleep apnea on neuromuscular transmission- a descriptive study

ABSTRACT Objective: Obstructive sleep apnea (OSA) is a sleep disorder accompanied by intermittent hypoxia. Neuromuscular transmission (NT) is known to be disturbed under chronic hypoxia. In this descriptive study, it has been aimed to test NT under intermittent hypoxia in OSA. Methods: Thirty-nine newly diagnosed OSA patients without any comorbidities or conditions that alter NT were included in the study. Jitter analysis was performed using a concentric needle electrode. Results: The mean jitter value of 39 OSA patients was 25.9 ± 3.7 μs. When compared to the mean reference jitter values, patients in the present study had significantly higher jitter (p < 0.001). Seven (17.9%) patients met the electrophysiological criteria for NT failure. Conclusion: The authors propose that intermittent hypoxia can be the trigger for NT failure in OSA. The interaction between increased oxidative stress and disturbed mitochondrial functions may also contribute.

158P Obstructive sleep apnea and breast cancer incidence: A systematic review and meta-analysis

Obstructive sleep apnea (OSA) is a prevalent form of sleep-disordered breathing. Emerging evidence from animal models suggests that intermittent nocturnal hypoxia in OSA may induce carcinogenesis. However, epidemiological studies have reported conflicting findings on this relationship. We conducted this systematic review and meta-analysis to evaluate the association between OSA and breast cancer - the most common cancer in women worldwide.

Relation of Obstructive Sleep Apnea in Patients With a Coronary Chronic Total Occlusion to Coronary Collaterals and Mortality

A chronic total occlusion (CTO) is frequently identified in patients undergoing coronary angiography. The prognostic implications of intermittent hypoxia from obstructive sleep apnea (OSA) on patients with a CTO, and effects on collateral recruitment are unknown. The aim of this study was to determine the prevalence, vascular effects, and prognostic implications of the presence of OSA in patients with a CTO. Patients with a CTO between July 2010 and December 2019 were reviewed. Electronic medical records were accessed to determine documented patient history of OSA, demographics, and clinical course. Patients with robust collateral recruitment were defined as Rentrop grade 2 or 3. A total of 948 patients were included in the study, of which 127 (13.4%) had a documented history of OSA. These patients were younger (67.0 years vs 70.6 years, p < 0.01), had a higher body mass index (29.6 kg/m2 vs 26.7 kg/m2, p < 0.0001), higher rates of hypertension (91.3% vs 83.2%, p < 0.05), higher rates of smokers (63.3% vs 49.0%, p < 0.01) and more use of β-blockers (79% vs 68.5%, p < 0.05) and statins (92.7% vs 82.1%, p < 0.01). A documented history of OSA was independently associated with robust collaterals (OR 3.0 95%CI 1.5 to 5.8, p < 0.01) and lower mortality (HR 0.3 95% CI 0.1 to 0.7, p < 0.01) with a mean survival of 10.8 years, as compared to 8.1 years (log rank p < 0.0001). In conclusion, in patients with a CTO, documented OSA is independently associated with more robust coronary collaterals and lower mortality. The possible cardioprotective implications of intermittent hypoxia in OSA, as well as treatment effect requires further investigation.

Association Of Nocturnal Intermittent Hypoxia With Heat Shock Protein 70 In Patients With Obstructive Sleep Apnea: A Pilot Study

Introduction — Nocturnal intermittent hypoxia in obstructive sleep apnea (OSA) causes cellular stress and consequent change in inducible heat shock protein 70 (HSP70) level. Thus, the objective of this study was to determine the relationship among nocturnal hypoxia and the serum HSP70 level in patients with severe OSA. Material and Methods — The study involved 34 patients with a clinical diagnosis of moderate to severe OSA (24 men and 10 women). Patients without OSA (10 men and 5 women) were included as a control group. The groups were similar in age. The polysomnographic monitoring was carried by standart methodology. Blood sampling for determining the HSP70 level was carried out between 8:00 and 9:00 am after polysomnographic monitoring. Results — The results of this study demonstrated a high apnea/hypopnea index (AHI), which determined the OSA severity and decreased the blood oxygen saturation (SaO2) (p&lt;0.05). Sleep fragmentation in OSA patients confirmed an increase in respiratory arousal index (ArI). The HSP70 level significantly increased in OSA patients compared with the control group. Correlation analysis showed a positive relationship between HSP70 and AHI (R=0.5) in patients with OSAS, as well as a negative relationship between HSP70 and SaO2 (R=-0.3). Conclusion — Our results demonstrated a high level of HSP70 in patients with severe OSA syndrome vs. those without it. In OSA patients, a direct correlation was found between the HSP70 level and AHI, as well as an inverse correlation between the AHI level and SaO2. These findings suggested an association between the level of inducible HSP70 and nocturnal hypoxia in OSA patients.

Associations between hypoxia parameters in obstructive sleep apnea and cognition, cortical thickness, and white matter integrity in middle-aged and older adults.

This study aimed to investigate the association between each parameter of intermittent hypoxia in obstructive sleep apnea (OSA) and the cognitive profile, cortical thickness, and white matter integrity in middle-aged and older adults. Participants were newly diagnosed with moderate or severe OSA from the King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Respiratory parameters from polysomnography were extracted. Each participant was tested on a battery of neuropsychological tests and underwent an MRI scan of the brain. Cortical thickness analysis and diffusion tensor imaging analysis were performed. Participants were classified as having either severe or mild hypoxia based on parameters of hypoxia, i.e., oxygen desaturation index, lowest oxygen saturation, and the percentage of total sleep time spent below 90% oxygen saturation. Of 17patientswith OSA, there were 8men (47%). Median age was 57 years and median AHI was 60.6. Comparison of cortical thicknessbetween the severe and themild group of each hypoxic parameter revealed two clusters of cortical thinning at the right inferior frontal gyrus (p-value = 0.008) and right inferior parietal gyrus (p-value = 0.006) in the severe desaturation group and a cluster of cortical thinning at the superior parietal gyrus (p-value = 0.008) in the high oxygen desaturation index group. There was no difference in cognitive function or white matter integrity between groups. The magnitude of the degree and frequency of desaturations in OSA are associated with a decrease in cortical thickness at the frontal and parietal regions.

Serum matrix metalloproteinase-2 as a predictor of level of hypoxemia and severity of obstructive sleep apnea

Intermittent hypoxia in obstructive sleep apnea (OSA) resembles ischemia/reperfusion. Oxidative stress during ischemia/reperfusion increases matrix metalloproteinase-2 (MMP-2) activity and leads to adverse cardiovascular consequences in animal models, but there is scarce information about MMP-2 in humans with OSA. The aim of this study was to determine if serum MMP-2 levels of patients with OSA differ from controls and if MMP-2 activity correlates with the severity of OSA andlevel of hypoxemia. Patientswith OSA (n = 124) were recruited from the Sleep Disorders Center (Saskatoon City Hospital, Canada) after in-lab polysomnography (PSG). Controls (n = 26) were subjects referred for PSG who did not have OSA. Severity of OSA was categorized according to American Academy of Sleep Medicine criteria. Level of hypoxemia was expressed as oxygen desaturation index (ODI; 3% desaturation). Gelatin zymography was performed to measure serum MMP-2 activity. Serum MMP-2 activity was significantly higher inpatients with OSA than in controls (p = 0.029). MMP-2 activity in patients with severe OSA was significantly higher than in those with mild/moderate OSA and controls (p = 0.002). Linear regression showed positive associations with MMP-2 activity in serum for AHI (p < 0.001) and ODI (p = 0.003). The associations persisted after adjustment for multiple confounders, including age, sex, BMI, and cardiovascular disease. Serum MMP-2 activity was associated with OSA severity, and level of hypoxemia inpatients with OSA, suggesting MMP-2 is worth considering as a potential biomarker to be included in future studies on sets of biomarkers for hypoxemic insult in OSA.

The Association of Sleep Disorders, Obesity and Sleep-Related Hypoxia with Cancer.

BackgroundSleep disorders have emerged as potential cancer risk factors.Objective This review discusses the relationships between sleep, obesity, and breathing disorders with concomitant risks of developing cancer.ResultsSleep disorders result in abnormal expression of clock genes, decreased immunity, and melatonin release disruption. Therefore, these disorders may contribute to cancer development. Moreover, in sleep breathing disorder, which is frequently experienced by obese persons, the sufferer experiences intermittent hypoxia that may stimulate cancer cell proliferation.DiscussionDuring short- or long- duration sleep, sleep-wake rhythm disruption may occur. Insomnia and obstructive sleep apnea increase cancer risks. In short sleepers, an increased risk of stomach cancer, esophageal squamous cell cancer, and breast cancer was observed. Among long sleepers (>9 hours), the risk of some hematologic malignancies is elevated.ConclusionSeveral factors including insomnia, circadian disruption, obesity, and intermittent hypoxia in obstructive sleep apnea are contributing risk factors for increased risk of several types of cancers. However, further studies are needed to determine the more significant of these risk factors and their interactions.

Patients with obstructive sleep apnea present with chronic upregulation of serum HIF-1α protein

Obstructive sleep apnea (OSA) is a chronic condition that is characterized by recurrent pauses in breathing during sleep causing intermittent hypoxia. The main factor responsible for oxygen metabolism homeostasis is hypoxia-inducible factor 1 (HIF-1), comprised of 2 subunits: α (oxygen sensitive) and β. The aim of the study was to investigate the HIF-1α serum protein level and mRNA HIF-1α expression in patients with OSA and a healthy control group and determine their evening-morning variation and association with polysomnography parameters. Eighty-four individuals were enrolled in the study. All patients underwent polysomnography examination and based on the results were divided into 2 groups: OSA group (n = 60) and control group (n = 24). Peripheral blood was collected in the evening before and in the morning after the polysomnography. HIF-1α expression was evaluated on protein in blood serum and mRNA level in peripheral blood leukocytes. HIF-1α serum protein concentration was higher in patients with OSA compared with control patients in both the evening (1,490.1 vs. 727.0 pg/mL; P < .001) and the morning (1,368.9 vs. 702.1 pg/mL; P < .001) samples. There was no difference between evening and morning HIF-1α serum protein level in either group. No differences were observed in HIF-1α mRNA expression between the OSA and control group. Additionally, evening and morning HIF-1α serum protein level correlated with number of desaturations during sleep (r = .384, P < .001 and r = .433, P < .001, respectively). Observed differences in HIF-1α serum protein level between the OSA and the control groups without difference between evening and morning measurements suggest chronic increase in this protein concentration by intermittent nocturnal hypoxia in OSA.

Chronic intermittent hypoxia in obstructive sleep apnea: a narrative review from pathophysiological pathways to a precision clinical approach.

Obstructive sleep apnea syndrome (OSAS) is a prevalent condition caused by dynamic upper airway collapse during sleep. The pathological impact and consequences are due to chronic intermittent hypoxia (CIH). Hypoxia increases the expression of several inflammatory stress markers and endothelial dysfunction. Recent studies suggest that patients with a similar AHI but with severe nocturnal hypoxia using oximetric parameters, such as the lowest saturation of oxygen during the night (min SaO2), percentage of total sleep time with oxygen saturation < 90% (T90) or the oxygen desaturation index (ODI-3%), commonly reported during the sleep study, are indicative of the increased expression of inflammatory markers due to severe nocturnal hypoxia and CIH during the night compared to subjects with moderate-severe OSAS without severe nocturnal hypoxia. The aim of this review is to describe physiological pathways involved in OSAS and their clinical consequences, focused in CIH and oximetric parameters showed in sleep study and their potential utility as inflammatory markers.

Peripheral Nerve Function Changes Due to Hypoxia in Obstructive Sleep Apnea

Peripheral Nerve Function Changes Due to Hypoxia in Obstructive Sleep Apnea

Obstructive sleep apnea is associated with altered midbrain chemical concentrations

Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age±SD:54.6±10.6years; AHI:35.0±19.4; SAO2 min:83±7%) and 26 healthy control (50.7±8.5years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting (ProFit) algorithm. The midbrain in OSA showed decreased N-acetylaspartate (NAA; OSA:1.24±0.43, Control:1.47±0.41; p=0.03; independent samples t-test), a marker of neuronal viability. Increased levels in OSA over control subjects appeared in glutamate (Glu; OSA:1.23±0.57, Control:0.98±0.33; p=0.03), ascorbate (Asc; OSA:0.56±0.28, Control:0.42±0.20; (50.7±8.5years; p=0.03), and myo-inositol (mI; OSA:0.96±0.48, Control:0.72±0.35; p=0.03). No differences between groups appeared in γ-aminobutyric acid (GABA) or taurine. The midbrain in OSA patients shows decreased NAA, indicating neuronal injury or dysfunction. Higher Glu levels may reflect excitotoxic processes and astrocyte activation, and higher mI is also consistent with glial activation. Higher Asc levels may result from oxidative stress induced by intermittent hypoxia in OSA. Additionally, Asc and Glu are involved with glutamatergic processes, which are likely upregulated in the midbrain nuclei of OSA patients. The altered metabolite levels help explain dysfunction and structural deficits in the midbrain of OSA patients.

Impact of age on intermittent hypoxia in obstructive sleep apnea: a propensity-matched analysis.

To determine independent relationship of aging with chronic intermittent hypoxia, we compared hypoxia-related polysomnographic variables of geriatric patients (aged ≥65years) with an apnea-hypopnea index (AHI)-, gender-, body mass index (BMI)-, and neck circumference-matched cohort of non-geriatric patients. The study was conducted using clinical and polysomnographic data of 1280 consecutive patients who underwent complete polysomnographic evaluation for suspected sleep-disordered breathing (SDB) at a single sleep disorder center. A propensity score-matched analysis was performed to obtain matched cohorts of geriatric and non-geriatric patients, which resulted in successful matching of 168 patients from each group. Study groups were comparable for gender (P=0.999), BMI (P=0.940), neck circumference (P=0.969), AHI (P=0.935), and severity of SDB (P=0.089). The oximetric variables representing the duration of chronic intermittent hypoxia such as mean (P=0.001), the longest (P=0.001) and total apnea durations (P=0.003), mean (P=0.001) and the longest hypopnea durations (P=0.001), and total sleep time with oxygen saturation below 90% (P=0.008) were significantly higher in the geriatric patients as compared with younger adults. Geriatric patients had significantly lower minimum (P=0.013) and mean oxygen saturation (P=0.001) than non-geriatric patients. The study provides evidence that elderly patients exhibit more severe and deeper nocturnal intermittent hypoxia than the younger adults, independent of severity of obstructive sleep apnea, BMI, gender, and neck circumference. Hypoxia-related polysomnographic variables in geriatric patients may in fact reflect a physiological aging process rather than the severity of a SDB.

Clarifying the Role of Hypoxia in Obstructive Sleep Apnea as a Potential Promulgator of Atrial Fibrillation in Ischemic Stroke.

Clarifying the Role of Hypoxia in Obstructive Sleep Apnea as a Potential Promulgator of Atrial Fibrillation in Ischemic Stroke.

Endothelial Cell-Derived Microparticles from Patients with Obstructive Sleep Apnea Hypoxia Syndrome and Coronary Artery Disease Increase Aortic Endothelial Cell Dysfunction

Background/Aims: Obstructive sleep apnea hypoxia syndrome (OSAHS) is an independent risk factor for coronary artery disease (CAD). Treatment of OSAHS improves clinical outcome in some CAD patients, but the relationship between OSAHS and CAD is complex. Microparticles (MPs) are shed by the plasma membrane by either physiologic or pathologic stimulation. In the current study, we investigated the role of MPs in the context of OSAHS. Methods and Results: 54 patients with both suspected coronary artery stenosis and OSAHS were recruited and underwent both coronary arteriography and polysomnography. Circulating MPs were isolated and analyzed by flow cytometry. CAD+OSAHS patients exhibited greater levels of total MPs (Annexin V⁺), erythrocyte-derived MPs (CD235⁺ Annexin V⁺), platelet-derived MPs (CD41⁺ Annexin V⁺), and leukocyte-derived MPs (CD45⁺ Annexin V⁺) compared to CAD alone patients or control. CAD+OSAHS patients expressed the greatest level of endothelial-derived MPs of all cellular origin types (CD144⁺ Annexin V ⁺). Treatment of human aortic endothelial cells (HAECs) with MPs isolated from CAD+OSAHS patients markedly increased HAEC permeability (as detected by FITC-dextran), and significantly upregulated mRNA levels of ICAM-1, VCAM-1, and MCP-1. Conclusion: OSAHS+CAD patients harbor increased levels of MPs, particularly the endothelial cell-derived subtype. When administered to HAECs, OSAHS+CAD patients MPs increase endothelial cell permeability and dysfunction.

Effect of obstructive sleep apnea hypoxia on learning memory capacity after cerebral ischemia-reperfusion in rats

To investigate the effect of obstructive sleep apnea hypoxia on learning memory capacity in rat after ischemia. Eighty healthy male wister rats were randomly divided into: sham operation group (SO group, n=20), merely ischemia group (I/R group, n=20), and obstructive sleep apnea hypoxia for 7 days ischemia group (IH7+ I/R group, n=20), obstructive sleep apnea hypoxia for 21 days ischemia group (IH21+ I/R group, n=20). Obstructive sleep apnea hypoxia ischemia groups were respectively given obstructive sleep apnea hypoxia for 7 days and 21 days. Ischemia animals were prepared cerebral ischemia-reperfusion model by improved pulsinelli four vessels block (4-VO), the morphological changes of hippocampus nerve cells of rat brain were detected with HE, neuron pathology in hippocampal regin was observed using electron microscope, and learning memory capacity of rats were assessed by the Morris water maze test. Compared with the SO group, the I/R group demonstrated shortened escaping latency, increased frequency of crossing the platform in the water maze test, decreased survival rate of neurons, and increased apoptotic cells and ultrastructure damages(P<0.05). Compared with the I/R group, obstructive sleep apnea hypoxia ischemia groups showed shortened escaping latency, increased frequency of crossing the platform, decreased survival rate of neurons, and increased apoptotic cells and ultrastructure damages(P<0.05), especially in the IH21+ I/R group(P<0.05). Obstructive sleep apnea hypoxia can increase the damage of learning memory capacity. This damage is related to hippocampus nerve loss and ultrastructure injury from obstructive sleep apnea hypoxia.

Intermittent Hypoxia Alters Gene Expression in Peripheral Blood Mononuclear Cells of Healthy Volunteers.

Obstructive sleep apnea is associated with high cardiovascular morbidity and mortality. Intermittent hypoxia of obstructive sleep apnea is implicated in the development and progression of insulin resistance and atherosclerosis, which have been attributed to systemic inflammation. Intermittent hypoxia leads to pro-inflammatory gene up-regulation in cell culture, but the effects of intermittent hypoxia on gene expression in humans have not been elucidated. A cross-over study was performed exposing eight healthy men to intermittent hypoxia or control conditions for five hours with peripheral blood mononuclear cell isolation before and after exposures. Total RNA was isolated followed by gene microarrays and confirmatory real time reverse transcriptase PCR. Intermittent hypoxia led to greater than two fold up-regulation of the pro-inflammatory gene toll receptor 2 (TLR2), which was not increased in the control exposure. We hypothesize that up-regulation of TLR2 by intermittent hypoxia may lead to systemic inflammation, insulin resistance and atherosclerosis in patients with obstructive sleep apnea.

Association Between the Severity of Nocturnal Hypoxia in Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Damage.

Background:Obstructive sleep apnea (OSA) is a major disease that can cause significant mortality and morbidity. Chronic intermittent hypoxia is a potential causal factor in the progression from fatty liver to nonalcoholic steatohepatitis.Objectives:This study evaluated the association between the degree of liver steatosis and severity of nocturnal hypoxia.Patients and Methods:In this study, between December 2011 and December 2013, patients with ultrasound-diagnosed NAFLD evaluated by standart polysomnography were subsequentally recorded. Patients with alcohol use, viral hepatitis and other chronic liver diseases were excluded. We analyzed polysomnographic parameters, steatosis level and severity of obstructive sleep apnea (OSA) in consideration of body mass index (BMI), biochemical tests and ultrasonographic liver data of 137 subjects. Patients with sleep apnea and AHI scores of < 5, 5 - 14, 15 - 29 and ≥30 are categorized as control, mild, moderate and severe, respectively.Results:One hundred and thirty-seven patients (76 women, 61 men) with a mean age of 55.75 ± 10.13 years who underwent polysomnography were included in the study. Of 118 patients diagnosed with OSA, 19 (16.1%) had mild OSA, 39 (33.1%) moderate OSA and 60 (50.8%) severe OSA. Nineteen cases formed the control group. Apnea/hypopnea index and oxygen desaturation index (ODI) values were significantly higher in moderate and severe non-alcoholic fatty liver disease (NAFLD) compared to the non-NAFLD group. Mean nocturnal SpO2 values were significantly lower in mild NAFLD and severe NAFLD compared to the non-NAFLD group. Lowest O2 saturation (LaSO2) was found low in mild, moderate and severe NAFLD compared to the non-NAFLD group in a statistically significant manner.Conclusions:We assessed polysomnographic parameters of AHI, ODI, LaSO2 and mean nocturnal SpO2 levels, which are especially important in the association between NAFLD and OSAS. We think that it is necessary to be attentive regarding NAFLD development and progression in patients with OSA whose nocturnal hypoxia is severe.