Dysfunction In Obstructive Sleep Apnea Patients Research Articles

Cortical activation during the verbal fluency task for obstructive sleep apnea patients with depressive symptoms: A multi-channel fNIRS study.

The aim of our study was to elucidate differences in brain activity patterns among obstructive sleep apnea (OSA) patients, OSA patients with depressive symptoms, and healthy controls (HCs). We also investigated the relationship between brain function and depression in OSA patients. A total of 95 subjects were included in the study, including 34 OSA patients without depressive symptoms, 31 OSA patients with depressive symptoms, and 30 HCs. The 53-channel functional near-infrared spectroscopy (fNIRS) was used to monitor the concentration of oxy-hemoglobin (Oxy-Hb) in the brain, whereas the participants performed the verbal fluency task, and the degree of depression was scored using the 17-item Hamilton Rating Scale for Depression (HAMD-17). Hierarchical regression models were conducted to analyze the association of fNIRS features with depressive symptom. The Oxy-Hb changes of the three groups were significantly different in Channels 25 (H=9.878, p=.007) and 43 (H=6.957, p=.031). Inter-group comparisons showed that the Oxy-Hb change of Channel 25 (located in the dorsolateral prefrontal cortex [DLPFC]) in OSA group was less than that in HC group (p=.006), and the Oxy-Hb change of Channel 43 (located in the right frontal polar region) in OSA group with depression was less than that in OSA group (p=.025). Spearman's test showed that there was a significant negative correlation between HAMD-17 scores and mean Oxy-Hb changes in Channel 43 (r=-.319, p<.05) in the OSA patients. Using hierarchical regression, Oxy-Hb changes in Channel 43 accounted for a significant proportion of the variation in outcome variables, even when accounting for other polysomnography features. Changes in the hemodynamic response of DLPFC may be a potential mechanism of executive dysfunction in OSA patients. And the right frontal polar region may be significant in assessing depressive symptoms in patients with OSA.

Passive Leg Movement as a Diagnostic Tool for Distinguishing Healthy Individuals from Those with Obstructive Sleep Apnea

Background – Obstructive Sleep Apnea (OSA) is linked with endothelial dysfunction, posing a significant risk for cardiovascular diseases. The non-invasive assessment of endothelial function through passive leg movement (PLM) offers a novel diagnostic avenue. This study explores PLM's efficacy in differentiating between healthy individuals and those with OSA, alongside evaluating the impact of oral vitamin C on endothelial function within these groups. Materials and Methods: The study enrolled 26 male subjects, divided equally into healthy and OSA groups. PLM was performed using an isokinetic machine to assess femoral artery blood flow (FBF) and blood velocities (FBVs) via Doppler ultrasound. Subjects consumed 1000mg of oral vitamin C, with measurements repeated post-consumption. Data analysis involved repeated measures ANOVA to evaluate the diagnostic capability of PLM and the effect of vitamin C on FBF responses. Results: A significant difference in FBF was observed between OSA and healthy groups (healthy: 162.1 ml/min, OSA: 76.6 ml/min; p &lt; 0.05), confirming PLM's diagnostic potential. However, vitamin C administration did not significantly alter FBF responses in OSA patients (pre-vitamin C: 76.6 ml/min, post-vitamin C: 79.9 ml/min; p &gt; 0.05), challenging the anticipated benefits of oral vitamin C on endothelial function. Conclusion: PLM effectively distinguishes between healthy individuals and those with OSA, highlighting its diagnostic utility. Nonetheless, oral vitamin C did not improve endothelial dysfunction in OSA patients, suggesting the need for further research on alternative administration methods or dosages.

PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea.

Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy. The expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using in vitro models. In addition, PSGL-1 impact on T-cells function was evaluated by ex vivo models. Data showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia. In conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.

NOCTURNAL HYPOXIA INDEXES ARE ASSOCIATED WITH LEFT VENTRICULAR REMODELING AND DIASTOLIC DYSFUNCTION IN OBSTRUCTIVE SLEEP APNEA PATIENTS

Objective: Echocardiography features of obstructive sleep apnea (OSA) are heart derangements as higher left ventricular mass index (LVMI) and left ventricular end-diastolic diameter, lower left ventricular ejection fraction (LVEF), and impaired diastolic function. The apnea/hypopnea index (AHI), the parameter currently used to define diagnosis and severity of OSA, poorly predicts cardiovascular damage, cardiovascular events, and mortality. Thus, we aimed to assess, if, in addition to AHI, other polygraphic indices of OSA presence and severity might serve as better predictors of echocardiographic cardiac remodeling. Design and method: We enrolled two cohorts of subjects referred for suspected OSA to the outpatient facilities of the IRCCS Istituto Auxologico Italiano, Milano, and of the Clinica Medica 3, Padova. All patients underwent home sleep apnea testing and echocardiography. Based on the AHI the cohort was divided into no-OSA (AHI&lt;15 events/hour) and moderate-severe OSA (AHI&gt; = 15 events/hour). A stepwise multiple regression analysis was used to identify the covariates among age, gender, body mass index, past medical history, and polygrapic variables, independently associated to four echocardiographic variables, e.g., LVMI, LVEF, left ventricular end-diastolic volume (LVEDV), early and late ventricular filling velocity ratio (E/A). Results: We recruited 162 patients and found that compared to patients with no-OSA, those with moderate-severe OSA showed higher LV remodeling [LVEDV 48.4±11.5 ml/m2 vs. 54.1±14.0 ml/m2, respectively, p = 0.005] and lower LVEF (65.3±5.8 % vs. 61.6±7.8%, respectively, p = 0.002), whereas we could not find any difference in LVMI and E/A. At multivariate linear regression analysis, the only polygraphic independent predictor of LVEDV was the percentage of time with SatO2 &lt; 90% (↓ = 0.262), whereas, the independent predictors of E/A were AHI (↓ = -0.379) and oxygen desaturation index (↓ = -0.422). None of the polygraphic variables was associated to LVMI and LVEF at multivariate linear regression analysis. Conclusions: Our study shows that nocturnal hypoxia-related indexes were associated with left ventricular remodeling and diastolic dysfunction in OSA patients. If confirmed in future studies with a wider sample of patients included, these results support the adoption of hypoxia indexes in the evaluation of OSA patients, particularly those at a greater cardiovascular risk.

Evaluation of auditory system in obstructive sleep apnea patients.

Obstructive sleep apnea (OSA) has been associated with auditory dysfunction both to the cochlear and higher auditory pathways. However, available literatures presented conflicting results. We aimed to study the impact of OSA severity and their polysomnography parameters on hearing function. A total of 44 patients were included after evaluation for sleep disorders and were divided into four groups in accordance with apnea-hypopnea index (AHI). Pure tone audiometry (PTA), distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) were compared in commensurate with the severity of AHI. Polysomnography oximetry parameters of oxygen desaturation index, mean SPO2, minimum SPO2 and percent SPO2 < 90% were correlated with their respective PTA, DPOAE and ABR results. There was no significant change in the PTA, DPOAE and ABR results in connection with AHI severity. However, we found significant correlations between mean SPO2 and percent SPO2 < 90% with ABR wave I, III and V absolute latencies. Minimum SPO2 was also significantly correlated with wave III peak latency changes. Mean SPO2, percent SPO2 < 90% and minimum SPO2 could be key prognostic indicators of central auditory dysfunction in OSA patients. These parameters should be explored further as indicators of OSA severity rather than utilizing AHI alone. The hypoxic burden derived could be a better predictor of auditory function abnormalities rather than one derived from AHI.

Reduced Cross-Frequency Coupling and Daytime Sleepiness in Obstructive Sleep Apnea Patients.

Simple SummaryObstructive sleep apnea (OSA) is one of the most common breathing-related sleep disorders. The processes that take place in specific areas of the brain during distinct sleep stages and specific respiratory events are suspected to be impaired in OSA patients. These brain processes may be described in complex (mathematical) terms. Using one of these descriptions (phase–amplitude cross-frequency coupling), we demonstrated in electroencephalographic (EEG) recordings of OSA patients that the process sequences in certain areas of the brain are altered in distinct sleep stages of OSA patients compared to patients who do not suffer from clinically relevant OSA. In addition, we were able to find a physiological marker that assesses the severity of daytime sleepiness, one of the main symptoms of OSA. This study supports the hypothesis that OSA is a neuronal/neuromuscular disorder. Thus, it contributes to a better understanding of the so-far-unexplained cause for the development of OSA and opens new possibilities for the exploration of alternative therapeutic approaches.Obstructive sleep apnea (OSA) is associated with sleep-stage- and respiratory-event-specific sensorimotor cortico-muscular disconnection. The modulation of phase–amplitude cross-frequency coupling (PACFC) may influence information processing throughout the brain. We investigated whether sleep-stage-specific PACFC is impaired at the sensorimotor areas in OSA patients. C3 and C4 electrode EEG polysomnography recordings of 170 participants were evaluated. Different frequency band combinations were used to compute CFC modulation index (MI) to assess if MI differs between OSA and non-significant OSA patients in distinct sleep stages. We tested if the CFC-MI could predict daytime sleepiness in OSA. Theta–gamma CFC-MI at cortical sensorimotor areas was significantly reduced during all sleep stages; the delta–alpha CFC-MI was significantly reduced during REM and N1 while increasing during N2 in patients with respiratory disturbance index (RDI) > 15/h compared to those with RDI ≤ 15/h. A sleep stage classification using MI values was achieved in both patient groups. Theta–gamma MI during N2 and N3 could predict RDI and Epworth Sleepiness Scale, while delta–alpha MI during REM predicted RDI. This increase in disconnection at the cortical sensorimotor areas with increasing respiratory distress during sleep supports a cortical motor dysfunction in OSA patients. The MI provides an objective marker to quantify subjective sleepiness and respiratory distress in OSA.

Myopathy of the upper airway in snoring and obstructive sleep apnea.

ObjectivePrevious reports of muscle changes in the upper airways of obstructive sleep apnea (OSA) patients have primarily been attributed to acquired nerve lesions due to snoring vibrations. The aim of this study was to investigate whether alterations reflecting muscle fiber injuries also occur in the upper respiratory tract of snoring and OSA patients and if these changes relate to upper airway dysfunction.MethodsMuscle changes in biopsies from the soft palate of 20 patients suffering from snoring and OSA were investigated with enzyme, immunohistochemical, and morphometric techniques. Biopsies from eight healthy non‐snoring subjects were used as controls. Swallowing dysfunction was assessed with videoradiography.ResultsFourteen patients had various degrees of swallowing dysfunction. The muscle samples from all the patients showed changes typical for both motor‐nerve lesions and muscle fiber injuries. The most common alterations reflecting myopathy were fibers having aggregates and disorganization of cytoskeletal proteins (15.5 ± 10.7%). Other changes were fibers with vacuole‐like structures (5.0 ± 4.4%), centrally positioned myonuclei (7.9 ± 4.8%), subsarcolemmal accumulations of nuclei, and various forms and sizes of ring fibers, that is, fibers where the myofilaments were disorganized peripherally (2.8 ± 2.8%).ConclusionThe results show that muscle changes mirroring both myopathy and neuropathy co‐exist in the upper airway of snoring OSA patients. These findings suggest muscle weakness as a contributing factor to the upper airway dysfunction in OSA patients.

Endothelin-1 and LOX-1 as Markers of Endothelial Dysfunction in Obstructive Sleep Apnea Patients.

Introduction: The search of biochemical markers of endothelial dysfunction: lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)—involved in atherosclerotic plaques formation—and endothelin-1 (ET-1)—potent vasoconstrictor-might help in detecting obstructive sleep apnea (OSA) patients at high risk of cardiovascular diseases. Material and Methods: In 71 OSA patients (apnoea/hypopnoea index, AHI 28.2 ± 17.9/hour) and in 21 healthy controls the serum levels of LOX-1 and ET-1 were measured. Results: There were increased levels of ET-1 (1.58 ± 0.65 vs. 1.09 ± 0.38 pg/mL; p < 0.001) but not of LOX-1 in OSA patients as compared with healthy controls. In the patients’ group ET-1 levels negatively correlated with serum LDL levels. LOX-1 levels positively correlated with fasting glucose levels and were higher in the patients with than without diabetes. Neither ET-1 nor LOX-1 correlated with OSA severity. In mild OSA patients, there was a negative correlation between LOX-1 and mean arterial oxygen saturation during sleep. In severe OSA patients, there was a positive correlation between LOX-1 levels and uric acid. Conclusion: There is endothelial dysfunction in OSA patients as indicated by increased serum levels of ET-1 and possibly endothelial dysfunction in diabetic OSA patients as indicated by increased serum levels of LOX-1 and its correlation with fasting glucose levels.

Hypoxia-induced Effects on ECG Depolarization by Time Warping Analysis during Recurrent Obstructive Apnea.

In this work, we evaluated a non-linear approach to estimate morphological variations in ECG depolarization, in the context of intermittent hypoxia (IH). Obstructive apnea sequences were provoked for 15 minutes in anesthetized Sprague-Dawley rats, alternating with equal periods of normal breathing, in a recurrent obstructive sleep apnea (OSA) model. Each apnea episode lasted 15 s, while the frequency used for each sequence was randomly selected. Average heartbeats obtained before the start and at the end of each episode, were delineated to extract only the QRS wave. Then, the segmented QRS waves were non-linearly aligned using the dynamic time warping (DWT) algorithm. Morphological QRS changes in both the amplitude and temporal domains were estimated from this alignment procedure. The hypoxic and basal segments were analyzed using ECG (lead I) recordings acquired during the experiment. To assess the effects of IH over time, the changes relative to the basal QRS wave were determined, in the intervals prior to each successive events until the end of the experiment. The results showed a progressive increase in the amplitude and time-domain morphological markers of the QRS wave along the experiment, which were strongly correlated with the changes in traditional QRS markers (r ≈ 0.9). Significant changes were found between pre-apnea and hypoxic measures only for the time-domain analysis (p<0.001), probably due to the short duration of the simulated apnea episodes.Clinical relevance Increased variability in ECG depolarization morphology during recurrent hypoxic episodes would be closely related to the expression of cardiovascular dysfunction in OSA patients.

The Neuropsychological Profile of Attention Deficits of Patients with Obstructive Sleep Apnea: An Update on the Daytime Attentional Impairment.

Introduction: Patients with obstructive sleep apnea (OSA) suffer from several neurocognitive disturbances. One of the neuropsychological processes most investigated in OSA patients is attention, but the results have been controversial. Here, we update the attention profile of OSA patients with the final aim to improve attention assessment, with a possible impact on clinical and medical-legal practices, in terms of which attention subdomains and parameters need consideration and which one is a high-risk OSA phenotype for attention dysfunctions. Method: For this purpose, we assessed 32 previously untreated OSA patients (26 men and 6 women) under 65 years of age (mean age 53.2 ± 7.3; mean education level 10.4 ± 3.4 years) suffering from moderate to severe sleep apnea and hypopnea (mean apnea-hypopnea index (AHI) 45.3 ± 22.9, range 16.1–69.6). A control group of 34 healthy participants matched with OSA patients for age, education level, and general cognitive functioning were also enrolled. The OSA patients and healthy participants were tested through an extensive computerized battery (Test of Attentional Performance, TAP) that evaluated intensive (i.e., alertness and vigilance) and selective (i.e., divided and selective) dimensions of attention and returned different outcome parameters (i.e., reaction time, stability of performance, and various types of errors). Data analysis: The data were analyzed by ANCOVA which compared the speed and accuracy performance of the OSA and control participants (cognitive reserve was treated as a covariate). The possible mechanisms underlying attention deficits in OSA patients were examined through correlation analysis among AHI, oxygenation parameters, sleepiness scores, and TAP outcomes and by comparing the following three phenotypes of patients: severe OSA and severe nocturnal desaturators (AHI++D+), severe OSA nondesaturators (AHI++D−), and moderate OSA nondesaturators (AHI+D−). Results: The results suggest that the OSA patients manifest deficits in both intensive and selective attention processes and that reaction time (RT) alone is ineffective for detecting and characterizing their problems, for which error analysis and stability of performance also have to be considered. Patients with severe OSA and severe hypoxemia underperformed on alertness and vigilance attention subtests. Conclusions: The data suggest the importance of evaluating attention deficits among OSA patients through several parameters (including performance instability). Moreover, the data suggest a multifaceted mechanism underlying attention dysfunction in OSA patients.

Lack of associations between thyroid function and obstructive sleep apnea severity in adults with prediabetes and diabetes mellitus.

Hypothyroidism is associated with a high frequency of obstructive sleep apnea (OSA). However, the prevalence of OSA in hypothyroid patients is not different from the general population in many reports. The importance of thyroid function screening in sleep-disordered breathing is still controversial. This study aimed to explore the association between thyroid dysfunction and OSA in the adults with prediabetes or diabetes mellitus type 2, who have very high prevalence of OSA. OSA was assessed using an in-home monitoring device, WatchPAT200. OSA severity was measured using apnea-hypopnea index (AHI), oxygen desaturation index (ODI), minimum oxygen saturation (minO2), and time spent under oxygen saturation < 90% (T90). Patients with pre-existing thyroid dysfunction were excluded. Participants included 70 men and 118 women with mean age 52.8 ± 10.9years and body mass index 28.2 ± 4.9kg/m2. One hundred forty participants (75%) had OSA, with a median AHI of 10.1 (interquartile range 4.8, 18.3). The percentage of positive thyroid autoantibody (thyroperoxidase and thyroglobulin antibody) was similar among the subjects with and without OSA. There was no correlation between the levels of thyroid function (TSH, FT3, FT4, TSH/FT3, and TSH/FT4 ratio) and the severity indices of OSA (AHI, ODI, minO2, and T90). These data do not support universal screening for thyroid dysfunction in OSA patients with diabetes or prediabetes.

A Novel Chip for Cyclic Stretch and Intermittent Hypoxia Cell Exposures Mimicking Obstructive Sleep Apnea.

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), plays a critical role in the pathogenesis of OSA-associated morbidities, especially in the cardiovascular and respiratory systems. Oxidative stress and inflammation induced by IH are suggested as main contributors of end-organ dysfunction in OSA patients and animal models. Since the molecular mechanisms underlying these in vivo pathological responses remain poorly understood, implementation of experimental in vitro cell-based systems capable of inducing high-frequency IH would be highly desirable. Here, we describe the design, fabrication, and validation of a versatile chip for subjecting cultured cells to fast changes in gas partial pressure and to cyclic stretch. The chip is fabricated with polydimethylsiloxane (PDMS) and consists of a cylindrical well-covered by a thin membrane. Cells cultured on top of the membrane can be subjected to fast changes in oxygen concentration (equilibrium time ~6 s). Moreover, cells can be subjected to cyclic stretch at cardiac or respiratory frequencies independently or simultaneously. Rat bone marrow-derived mesenchymal stem cells (MSCs) exposed to IH mimicking OSA and cyclic stretch at cardiac frequencies revealed that hypoxia-inducible factor 1α (HIF-1α) expression was increased in response to both stimuli. Thus, the chip provides a versatile tool for the study of cellular responses to cyclical hypoxia and stretch.

Abnormal resting-state functional connectivity within the default mode network subregions in male patients with obstructive sleep apnea.

Background and objectiveAbnormal resting-state functional connectivity (rs-FC) between the central executive network and the default mode network (DMN) in patients with obstructive sleep apnea (OSA) has been reported. However, the effect of OSA on rs-FC within the DMN subregions remains uncertain. This study was designed to investigate whether the rs-FC within the DMN subregions was disrupted and determine its relationship with clinical symptoms in patients with OSA.MethodsForty male patients newly diagnosed with severe OSA and 40 male education- and age-matched good sleepers (GSs) underwent functional magnetic resonance imaging (fMRI) examinations and clinical and neuropsychologic assessments. Seed-based region of interest rs-FC method was used to analyze the connectivity between each pair of subregions within the DMN, including the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), hippocampus formation (HF), inferior parietal cortices (IPC), and medial temporal lobe (MTL). The abnormal rs-FC strength within the DMN subregions was correlated with clinical and neuropsychologic assessments using Pearson correlation analysis in patients with OSA.ResultsCompared with GSs, patients with OSA had significantly decreased rs-FC between the right HF and the PCC, MPFC, and left MTL. However, patients with OSA had significantly increased rs-FC between the MPFC and left and right IPC, and between the left IPC and right IPC. The rs-FC between the right HF and left MTL was positively correlated with rapid eye movement (r=0.335, P=0.035). The rs-FC between the PCC and right HF was negatively correlated with delayed memory (r=-0.338, P=0.033).ConclusionOSA selectively impairs the rs-FC between right HF and PCC, MPFC, and left MTL within the DMN subregions, and provides an imaging indicator for assessment of cognitive dysfunction in OSA patients.

Left ventricular subclinical dysfunction associated with myocardial deformation changes in obstructive sleep apnea patients estimated by real-time 3D speckle-tracking echocardiography.

Previous studies have demonstrated that patients with obstructive sleep apnea (OSA) may develop left ventricular (LV) diastolic dysfunction. We aimed to study whether OSA patients have LV regional systolic dysfunction with myocardial deformation changes, despite a normal LV ejection fraction, using real-time 3D speckle-tracking echocardiography (Rt3D-STE). Seventy-eight patients with OSA and no comorbidities were studied. They were divided into the following three groups according to the apnea-hypopnea index (AHI): 5~15/h as group I (mild OSA, 26 cases), 15~30/h as group II (moderate OSA, 29 cases), and ≥30/h as group III (severe OSA, 23 cases). Thirty gender-age-matched normal subjects were included as controls. The parameters of LV diastolic function were acquired with traditional echocardiography. The LV myocardial deformation parameters were obtained, including the longitudinal (LS), circumferential (CS), radial (RS), and area (AS) strains, with Rt3D-STE. LV global systolic function was normal in all patients, but diastolic function was impaired in groups II and III (E/E' was 9.6 ± 2.8 and 10.4 ± 2.5, respectively, p < 0.0001). The global LS and AS were significantly reduced in groups II and III compared with the controls and group I (LS 15.9 ± 1.4 % and 14.8 ± 1.5 % vs 18.2 ± 1.7 % and 17.8 ± 1.5 %; AS 27.4 ± 1.8 % and 24.9 ± 2.3 % vs 33.4 ± 2.2 % and 32.7 ± 2.9 %, respectively, p < 0.0001), but the global CS and RS were significantly reduced only in group III (17.3 ± 1.4 % and 43.1 ± 6.5 % vs 19.6 ± 1.6 % and 55.4 ± 4.0 %, respectively, <0.0001). The severity of OSA was significantly associated with the LV global AS value (r = -0.80, p < 0.0001), LS (r = -0.64, p < 0.0001), CS (r = -0.51, p < 0.0001), and RS (r = -0.62, p < 0.0001). Patients with moderate and severe OSA tended to have both LV diastolic dysfunction and abnormalities in regional systolic function with myocardial deformation changes, in spite of the normal LV ejection fraction. Myocardial strains of the LV were negatively correlated with the AHI. Rt-3DST had important clinical significance in the early evaluation of cardiac dysfunction in OSA patients.

Right Ventricular Dysfuction In Subject With Obstructive Sleep Apnoea

An analytical design study on the systolic right ventricle (RV) functionwas done in Obstructive Sleep Apnea (OSA) patients who underwentpolisomnography procedure and compare it with normal subject. Theassessment of the RV function was performed using the Speckle trackingechocardiography method. Other RV function parameters such as TAPSE,Tissue Doppler Imaging (TDI), dan Myocardial Performance Index (MPI)were also measured.The results showed RV dysfunction in OSA patients compared with normalsubject, the decrease of RV function was significantly different betweenthe two groups. Factors that contributed to RV dysfunction in OSA patientswere higher Apnea-Hypopnea Index (AHI) and Nocturnal OxygenDesaturation.

Endothelial nitric oxide synthase uncoupling: A novel pathway in OSA induced vascular endothelial dysfunction

The mechanism of vascular endothelial dysfunction (VED) and cardiovascular disease in obstructive sleep apnea (OSA) is unknown. We performed a comprehensive evaluation of endothelial nitric oxide synthase (eNOS) function directly in the microcirculatory endothelial tissue of OSA patients who have very low cardiovascular risk status. Nineteen OSA patients underwent gluteal biopsies before, and after effective treatment of OSA. We measured superoxide (O2•−) and nitric oxide (NO) in the microcirculatory endothelium using confocal microscopy. We evaluated the effect of the NOS inhibitor l-Nitroarginine-Methyl-Ester (l-NAME) and the NOS cofactor tetrahydrobiopterin (BH4) on endothelial O2•− and NO in patient endothelial tissue before and after treatment. We found that eNOS is dysfunctional in OSA patients pre-treatment, and is a source of endothelial O2•− overproduction. eNOS dysfunction was reversible with the addition of BH4. These findings provide a new mechanism of endothelial dysfunction in OSA patients and a potentially targetable pathway for treatment of cardiovascular risk in OSA.

Cognitive dysfunction in patients with obstructive sleep apnea (OSA): partial reversibility after continuous positive airway pressure (CPAP)

The aims of this study were to assess cognitive function in obstructive sleep apnea (OSA) patients and to evaluate the effect of short- and long-term treatment with continuous positive airway pressure treatment (CPAP). A battery of neuropsychological tests, the Epworth Sleepiness Scale (ESS), and the Beck Inventory Scale were administered to 23 patients with severe OSA (age: 56.5±6.13; AHI: 54.9±13.37) and to 23 age- and education-matched controls. The OSA patients were evaluated in a baseline condition and in two follow-up treatment sessions (after 15 days and 4 months of CPAP, respectively). At baseline, OSA patients had a significant impairment, compared to controls, in tests of sustained attention, visuospatial learning, executive function, motor performance, and constructional abilities. The longitudinal evaluation showed that after a 15-days CPAP treatment attentive, visuospatial learning, and motor performances returned to normal levels. A 4-months CPAP treatment did not result in any further improvement in cognitive tests. Performance on tests evaluating executive functions and constructional abilities was not affected by short- and long-term treatment with CPAP. The findings of this study confirm the hypothesis of partial reversibility of cognitive dysfunction in OSA patients after CPAP.