Oxidative and carbonyl stress in pregnant women with obstructive sleep apnea

Sleep and Breathing - Pregnant women are particularly susceptible to sleep-disordered breathing. Obstructive sleep apnea (OSA) in pregnancy is associated with poor pregnancy and fetal outcomes....     

The association of oxidative stress with central obesity in obstructive sleep apnea

Purpose  

The purpose of this paper is to evaluate concentrations of multiple oxidative stress and antioxidant status markers in patients with obstructive sleep apnea (OSA) and normal controls of comparable obesity.     

Oxidative stress in obstructive sleep apnea

STUDY OBJECTIVES: To investigate the relationship between the severity of obstructive sleep apnea (OSA) and oxidative stress, which plays an important role in the pathogenesis of cardiovascular disease, and to elucidate the factors contributing to this relationship. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 128 consecutive subjects referred to the sleep laboratory of our hospital for screening or treatment of OSA. INTERVENTIONS: Not applicable. MEASUREMENTS: The severity of sleep-disordered breathing was evaluated by polysomnography. We measured urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an in vivo parameter of oxidative stress. Known risk factors for oxidative stress (age, obesity, smoking, hyperlipidemia, hypertension, and diabetes mellitus) were also investigated. RESULTS: Seventy subjects had nonsevere OSA (an apnea-hypopnea index [AHI] < 30), and 58 subjects had severe OSA (AHI >or= 30). Urinary 8-OHdG excretion was significantly higher in the severe OSA group (p = 0.03). Furthermore, urinary 8-OHdG excretion was significantly correlated with parameters of sleep-disordered breathing, including AHI, the apnea index, the oxygen desaturation index (ODI), the duration of oxygen saturation < 90%, and the respiratory arousal index. However, only ODI was significantly correlated with urinary 8-OHdG excretion after adjustment for confounding factors that are considered to be related to oxidative stress. CONCLUSIONS: The severity of OSA is independently associated with oxidative stress. Among various sleep-disordered breathing parameters, ODI is most closely related to oxidative stress.     

Oxidative and carbonyl stress in patients with obstructive sleep apnea treated with continuous positive airway pressure

Purpose  

The pathogenesis of cardiovascular complications of obstructive sleep apnea syndrome (OSAS) can be explained by oxidative and carbonyl stress due to oxygenation and reoxygenation injury during sleep. This hypothesis has yet to be proved experimentally, although several clinical observations have found increased oxidative damage in plasma. Continuous positive airway pressure (CPAP) improves symptoms and prognosis of patients with OSAS.     

Cardiovascular morbidity in obstructive sleep apnea: oxidative stress, inflammation, and much more

Sleep-disordered breathing and obstructive sleep apnea (OSA) are highly prevalent disorders throughout the lifespan, which may affect up to 2-10% of the population, and have now been firmly associated with an increased risk for cardiovascular and neurobehavioral complications. Nevertheless, the overall pathophysiologic mechanisms mediating end-organ injury in OSA remain undefined, particularly due to the very frequent coexistence of other disease states, such as obesity, that clearly complicate the potential cause-effect relationships. Two major, and to some extent overlapping, mechanisms have been proposed to explain the morbid consequences of OSA, namely increased generation and propagation of reactive oxygen species and initiation and amplification of inflammatory processes. The evidence supporting the validity of these concepts as well as that detracting from such mechanisms will be critically reviewed in the context of clinical and laboratory-based approaches. In addition, some of the contradictory issues raised by such evaluation of the literature will be interpreted in the context of putative modifications of the individual responses to OSA, as determined by genetic variants among susceptibility-related genes, and also by potential environmental modulators of the phenotypic expression of any particular end-organ morbidity associated with OSA.     

The role of antioxidant vitamins and selenium in patients with obstructive sleep apnea

Sleep and Breathing - Obstructive sleep apnea (OSA) is a disorder characterized by recurrent episodes of obstruction of&nbsp;the upper respiratory tract during sleep&nbsp;often accompanied...     

Antioxidant vitamin C improves endothelial function in obstructive sleep apnea

RATIONALE: Obstructive sleep apnea (OSA) is associated with oxidative stress, endothelial dysfunction, and increased cardiovascular morbidity and mortality. OBJECTIVE: We tested the hypothesis that endothelial dysfunction in patients with OSA is linked to oxidative stress. METHODS: In the present study, we measured flow-mediated dilation (FMD) of the brachial artery by ultrasound in 10 otherwise healthy, untreated patients with OSA and 10 age-and sex-matched control subjects without sleep-disordered breathing before and after intravenous injection of the antioxidant vitamin C. The investigator performing the FMD measurements was blinded to the status of the patients. RESULTS: When compared with control subjects, baseline FMD was significantly reduced in the patients with OSA. After intravenous injection of 0.5 g vitamin C, vasoreactivity remained unchanged in the control subjects. In the patients with OSA, ascorbate led to an increase in FMD to a level comparable to that observed in the control group. CONCLUSION: The reduced endothelial-dependent vasodilation in untreated patients with OSA acutely improves by the free radical scavenger vitamin C. These results are in favor of oxidative stress being responsible for the endothelial dysfunction in OSA. Antioxidant strategies should be explored for the treatment of OSA-related cardiovascular disease.     

Neurobehavioral effects of obstructive sleep apnea: an overview and heuristic model

PURPOSE OF REVIEW: Obstructive sleep apnea can cause significant daytime behavioral and adaptive deficits, conventionally called 'neurobehavioral' because they are presumed to be mediated by the brain. The past few years have witnessed a marked increase in research into the neurobehavioral effects of obstructive sleep apnea, making it difficult for researchers and clinicians to stay abreast of the field. This article summarizes recent findings on the neurobehavioral effects of adult and pediatric obstructive sleep apnea, and presents a heuristic model to guide future research and clinical conceptualizations. RECENT FINDINGS: Recent publications have suggested overlapping but distinct neurobehavioral deficits that tend to accompany obstructive sleep apnea in the adult versus childhood years. There have been exciting new developments into the mechanisms by which obstructive sleep apnea may result in these deficits, including findings based upon advanced neuroimaging tools and carefully controlled animal research. There has also been accumulating evidence for potential moderators of morbidity; that is, factors that alter the nature or severity of neurobehavioral deficit resulting from obstructive sleep apnea. Task- and context-related factors that may affect outcome have been identified, as have potential markers for individual risk and resiliency. SUMMARY: The relation between obstructive sleep apnea and neurobehavioral deficit is probably not dependent on a single mediating mechanism, nor is it invariant across individuals. In outlining several potential moderating factors, the model presented here was designed to provide a guide for future research and a way of thinking about obstructive sleep apnea that better captures the wide variation in neurobehavioral outcome seen by practicing clinicians.     

Oxidative stress in patients with obstructive sleep apnea syndrome

Purpose

We aimed to investigate whether systemic oxidative stress is increased in patients with obstructive sleep apnea syndrome (OSAS).

Methods

A total of 18 patients with severe OSAS and 13 controls were included in the study. Inclusion criteria for OSAS patients were: snoring and apnea–hypopnea index (AHI) of >30 in full polysomnography, no previous treatment for OSAS, non-smoking status, and a medical history of being free of comorbidities known to increase oxidative stress. Controls were recruited among subjects assessed for snoring in the Sleep Laboratory Department if they had AHI<5. At baseline, patients were evaluated by the Epworth Sleepiness Scale and underwent spirometry, echocardiography, and full polysomnographic study. Blood samples were collected for evaluation of oxidative stress biomarkers [protein carbonyls, reduced (GSH) and oxidized (GSSG) glutathione, 8-isoprostane, thiobarbituric acid-reactive substances (TBARS), catalase activity, Cu–Zn superoxide dysmutase (SOD), total antioxidant capacity (TAC)] before and on the morning following polysomnography.

Results

The overnight (morning–night) change (%) of GSH/GSSG ratio and GSH was significantly different between OSAS and controls (p?=?0.03 and p?=?0.048, respectively). Plasma protein carbonyls, erythrocyte catalase activity, 8-isoprostane, SOD, TBARS, and TAC plasma values were not different between OSAS and controls (p?>?0.05). No significant correlation was found between changes in the levels of biomarkers and AHI, arousal, or desaturation index.

Conclusion

The present prospective investigation in a population free of comorbidities or factors which may increase systemic oxidative stress provides evidence that obstructive sleep apnea per se might be associated with increased oxidative burden possibly via GSH/GSSG pathway.     

氧化应激和内皮功能在 OSAHS并发高血压中的作用

目的：探讨氧化应激和血管内皮功能障碍在 OSAHS 并发高血压(hypertension,HT)发病机制中的作用,并观察经鼻气道持续正压通气(nasal continuous positive airway pressure,n-CPAP)治疗对 OSAHS 并发 HT 患者体内氧化应激、内皮功能及血压的影响。方法将研究对象分为 OSAHS 伴HT 组(35例)、n-CPAP 治疗组(10例)、OSAHS 不伴 HT 组(以下简称为 OSAHS 组,32例)、HT 组(31例)和健康对照组(34例)。应用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)测定血清中8-羟化脱氧鸟苷(8-hydroxy-2′-deoxyguanosine,8-OHdG)、内皮素-1(endothelin-1,ET-1)、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)及血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)水平;测定24 h 动态血压(ambulatory blood pressure,ABP)。结果 OSAHS 伴 HT 组及OSAHS 组患者血清8-OHdG、ET-1水平均明显高于健康对照组和 HT 组(P 值均<0.01),且 OSAHS伴 HT 组患者血清8-OHdG、ET-1水平均明显高于 OSAHS 组(P 值均<0.01);OSAHS 伴 HT 组血清VEGF 水平明显高于健康对照组、HT 组及 OSAHS 组(P 值均<0.01);OSAHS 伴 HT 组及 OSAHS 组血清 eNOS 水平明显低于健康对照组和 HT 组(P 值均<0.01),且 OSAHS 伴 HT 组血清 eNOS 水平低于 OSAHS 组(P <0.05)。OSAHS 伴 HT 组重度患者血清8-OHdG、ET-1、VEGF 水平及24 h 平均收缩压(mean systolic blood pressure,MSBP)、平均舒张压(mean diastolic blood pressure,MDBP)均明显高于轻、中度患者(P 值均<0.01),而血清 eNOS 水平则明显低于轻、中度患者(P <0.01)。所有研究对象血清8-OHdG 水平与血清 ET-1和 VEGF 水平均呈正相关(P <0.01和 P =0.01),而与血清 eNOS水平呈负相关(P <0.01)。经 n-CPAP 治疗7 d 后10例重度 OSAHS 伴 HT 患者血清8-OHdG、ET-1及 VEGF 水平均显著下降(P 值均<0.01),血清 eNOS 水平显著升高(P <0.01);24 h MSBP 和 MDBP均得到显著改善(P 值均<0.01)。结论内皮功能障碍与氧化应激相关,二者共同参与了 OSAHS 并发 HT 的发病机制;n-CPAP 治疗可通过抑制氧化应激而改善 OSAHS 伴 HT 患者的血管内皮功能,是OSAHS 并发 HT 患者的有效降压措施。     

Antioxidant vitamins attenuate oxidative stress and cardiac dysfunction in tachycardia-induced cardiomyopathy.

OBJECTIVES: We administered antioxidant vitamins to rabbits with pacing-induced cardiomyopathy to assess whether antioxidant therapy retards the progression of congestive heart failure (CHF). BACKGROUND: Although oxidative stress is increased in CHF, whether progression of heart failure could be prevented or reduced by antioxidants is not known. METHODS: Rabbits with chronic cardiac pacing and sham operation were randomized to receive a combination of beta-carotene, ascorbic acid and alpha-tocopherol, alpha-tocopherol alone or placebo over eight weeks. Echocardiography was used to measure cardiac function weekly. Resting hemodynamics and in vivo myocardial beta-adrenergic responsiveness were studied at week 8. Animals were then sacrificed for measuring myocardial beta-receptor density, norepinephrine (NE) uptake-1 site density, sympathetic neuronal marker profiles, tissue-reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and oxidative damage of mitochondrial DNA (mtDNA). RESULTS: Rapid cardiac pacing increased myocardial oxidative stress as evidenced by reduced myocardial GSH/GSSG ratio and increased oxidized mtDNA and produced cardiac dysfunction, beta-adrenergic subsensitivity, beta-receptor downregulation, diminished sympathetic neurotransmitter profiles and reduced NE uptake-1 carrier density. A combination of antioxidant vitamins reduced the myocardial oxidative stress, attenuated cardiac dysfunction and prevented myocardial beta-receptor downregulation and sympathetic nerve terminal dysfunction. Administration of alpha-tocopherol alone produced similar effects, but the effects were less marked than those produced by the three vitamins together. Vitamins produced no effects in sham-operated animals. CONCLUSIONS: Antioxidant vitamins reduced tissue oxidative stress in CHF and attenuated the associated cardiac dysfunction, beta-receptor downregulation and sympathetic nerve terminal abnormalities. The findings suggest that antioxidant therapy may be efficacious in human CHF.     

Hepatic oxidative stress in an animal model of sleep apnoea: effects of different duration of exposure

Background  

Repeated apnoea events cause intermittent hypoxia (IH), which alters the function of various systems and produces free radicals and oxidative stress.