Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice

2007 ◽  
Vol 102 (5) ◽  
pp. 1806-1814 ◽  
Author(s):  
Ah-Mee Park ◽  
Yuichiro J. Suzuki
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Damage ◽  
Obstructive Sleep ◽  
Increased Risk

Obstructive sleep apnea is associated with increased risk for cardiovascular diseases. As obstructive sleep apnea is characterized by episodic cycles of hypoxia and normoxia during sleep, we investigated effects of intermittent hypoxia (IH) on ischemia-reperfusion-induced myocardial injury. C57BL/6 mice were subjected to IH (2 min 6% O2 and 2 min 21% O2) for 8 h/day for 1, 2, or 4 wk; isolated hearts were then subjected to ischemia-reperfusion. IH for 1 or 2 wk significantly enhanced ischemia-reperfusion-induced myocardial injury. However, enhanced cardiac damage was not seen in mice treated with 4 wk of IH, suggesting that the heart has adapted to chronic IH. Ischemia-reperfusion-induced lipid peroxidation and protein carbonylation were enhanced with 2 wk of IH, while, with 4 wk, oxidative stress was normalized to levels in animals without IH. H2O2 scavenging activity in adapted hearts was higher after ischemia-reperfusion, suggesting the increased antioxidant capacity. This might be due to the involvement of thioredoxin, as the expression level of this protein was increased, while levels of other antioxidant enzymes were unchanged. In the heart from mice treated with 2 wk of IH, ischemia-reperfusion was found to decrease thioredoxin. Ischemia-reperfusion injury can also be enhanced when thioredoxin reductase was inhibited in control hearts. These results demonstrate that IH changes the susceptibility of the heart to oxidative stress in part via alteration of thioredoxin.

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

2020 ◽  
Vol 21 (6) ◽  
pp. 444-453
Author(s):  
Anna Brzecka ◽  
Karolina Sarul ◽  
Tomasz Dyła ◽  
Marco Avila-Rodriguez ◽  
Ricardo Cabezas-Perez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sleep Disorders ◽  
Intermittent Hypoxia ◽  
Clock Genes ◽  
Cell Cancer ◽  
Cancer Risk Factors ◽  
Obstructive Sleep ◽  
Increased Risk

Background: Sleep 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. Results: Sleep 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. Discussion: During 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. Conclusion: Several 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.

scholarly journals Obstructive Sleep Apnea and Circulating Biomarkers of Oxidative Stress: A Cross-Sectional Study

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 476
Author(s):  
Bernardo U. Peres ◽  
AJ Hirsch Allen ◽  
Aditi Shah ◽  
Nurit Fox ◽  
Ismail Laher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Smoking History ◽  
Obstructive Sleep ◽  
History Of ◽  
Statin Usage ◽  
The Impact

Oxidative stress (OS) drives cardiometabolic diseases. Intermittent hypoxia consistently increases oxidative stress markers. Obstructive sleep apnea (OSA) patients experience intermittent hypoxia and an increased rate of cardiovascular disease, however, the impact of OSA on OS markers is not clear. The objective was to assess relationships between OSA severity and biomarker levels. Patients with suspected OSA referred for a polysomnogram (PSG) provided fasting blood sample. Plasma levels of 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), and superoxide dismutase (SOD) were measured. The relationship between OSA and OS was assessed both before and after controlling for confounders (age, sex, smoking history, history of cardiovascular disease, ethnicity, diabetes, statin usage, body mass index (BMI)). 402 patients were studied (68% male, mean age ± SD = 50.8 ± 11.8 years, apnea-hypopnea index (AHI) = 22.2 ± 21.6 events/hour, BMI = 31.62 ± 6.49 kg/m2). In a multivariable regression, the AHI significantly predicted 8-isoprostane levels (p = 0.0008) together with age and statin usage; AHI was not a predictor of 8-OHdG or SOD. Female sex (p < 0.0001) and no previous history of cardiovascular disease (p = 0.002) were associated with increased antioxidant capacity. Circulating 8-isoprostane levels may be a promising biomarker of the severity of oxidative stress in OSA patients. Prospective studies are needed to determine whether this biomarker is associated with long-term cardiometabolic complications in OSA.

Abstract 466: Obstructive Sleep Apnea And Its Association With Endothelial Function, Oxidative Stress, Inflammation, Metabolic Profile, Blood Pressure And Sympathetic Activity In Obese Individuals

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Luciene S Araújo ◽  
Julia F Fernandes ◽  
Debora C Valença ◽  
Maria de Lourdes G Rodrigues ◽  
Nathalia F Gomes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Endothelial Function ◽  
Metabolic Profile ◽  
Neck Circumference ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
Hs Crp

Background: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease (CVD). Several of the proposed mechanisms for the development of CVD in OSA are similar to those proposed for the increased risk of CVD in obesity, being difficult to determine the influence of OSA on these pathogenic mechanisms in obese individuals. Objectives: The purpose of this study was to evaluate the relationship of OSA with endothelial function, oxidative stress, inflammatory biomarkers, metabolic profile, sympathetic nervous system activity and blood pressure (BP) in obese individuals. Methods: In this cross-sectional study, were included 53 obese adults (28 women). Sleep study was performed with Watch-PAT200® and the diagnosis of OSA was made when apnea-hipopnea index (AHI) ≥5 events/h (n=33). All participants underwent evaluation of: body adiposity, BP, plasma catecholamines, high sensitivity C-reactive protein (hs-CRP), adiponectin, malondialdehyde, glucose, insulin, lipid profile and endothelial function (Endo-PAT 2000®). Results: Mean age (39.6 ± 1.5 vs. 32.5 ± 2.1y) and percentage of male participants (61% vs. 25%) were significantly higher in participants with OSA than in those without OSA (p=0.01). In univariate analysis participants with OSA compared with those without OSA exhibited higher values of neck circumference (40.98 ± 0.63 vs. 38.65 ± 0.75 cm, p=0.02), glucose (92.54 ± 1.97 vs. 80.2 ± 1.92 mg/dL, p=0.0001), noradrenaline (0.16±0.02 vs. 0.12±0.03 ng/mL, p=0.02) and systolic BP (126.05 ± 1.61 vs. 118.16 ± 1.86 mmHg, p=0.003). After adjustment for confounders, only glucose and hs-CRP were significantly higher in OSA patients. In correlation analysis, after controlling for confounders, AHI was associated with neck circumference (r=0.31,p=0.03) and hs-CRP (r=0.30,p=0.04), while minimum O2 saturation was associated with neck circumference (r=-0.31,p=0.03), insulin (r=-0.29,p=0.04) and HOMA-IR (r=-0.30,p=0.04). Conclusion: The present study suggests that in obese individuals OSA is associated with inflammation and worse glycemia; higher AHI correlates with increased central adiposity and inflammation; and lower oxygen saturation is related with insulin resistance.

Influence of obstructive sleep apnea on ischemia-modified albumin levels and carotid intima-media thickness

2016 ◽  
Vol 64 (5) ◽  
pp. 1035-1041 ◽  
Author(s):  
Harun Karamanli ◽  
Aysel Kiyici ◽  
Bilal Arik ◽  
Duran Efe ◽  
Recep Akgedik
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Control Group ◽  
Ischemia Modified Albumin ◽  
Media Thickness ◽  
Obstructive Sleep ◽  
Increased Risk

Obstructive sleep apnea (OSA) is associated with an increased risk of atherosclerosis. Carotid intima-media thickness (CIMT) is strongly associated with the presence of significant risk factors for cardiovascular disturbances. A disturbance in the oxidative/antioxidative balance is involved in the pathogenesis of OSA and cardiovascular diseases. Ischemia-modified albumin (IMA) is suggested as a novel marker of oxidative stress; IMA can be defined as decreased binding of transitional metal ions to serum albumin in oxidative status. The purpose of this research was to evaluate the influence of OSA on IMA levels and CIMT. In total, 61 individuals with OSA with no comorbidities and 24 healthy controls with a similar body mass index and age were enrolled in this study. Serum levels of IMA, CIMT (estimated radiologically), and polysomnographic parameters, were determined and interpreted. Serum IMA levels were significantly higher in individuals with OSA compared with the control group (p=0.0003). CIMT was significantly higher in the OSA group compared with the control group (0.88± 0.26 mm vs 0.75±0.17 mm, p=0.005). The CIMT and serum IMA levels were positively correlated with the apnea-hypopnea index (r=0.35 and r=0.32, respectively), and with the oxygen desaturation index (r=0.34 and r=0.29, respectively) at baseline. Increased IMA levels and CIMT may be related to increased oxidative stress and risk of atherosclerosis in individuals with OSA.

scholarly journals Simulating obstructive sleep apnea patients' oxygenation characteristics into a mouse model of cyclical intermittent hypoxia

2015 ◽  
Vol 118 (5) ◽  
pp. 544-557 ◽  
Author(s):  
Diane C. Lim ◽  
Daniel C. Brady ◽  
Pengse Po ◽  
Li Pang Chuang ◽  
Laise Marcondes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mouse Model ◽  
Mouse Models ◽  
Intermittent Hypoxia ◽  
Molecular Signatures ◽  
Rodent Models ◽  
Obstructive Sleep ◽  
And Oxidative Stress

Mouse models of cyclical intermittent hypoxia (CIH) are used to study the consequences of both hypoxia and oxidative stress in obstructive sleep apnea (OSA). Whether or not a mouse model of CIH that simulates OSA patients' oxygenation characteristics would translate into improved patient care remains unanswered. First we identified oxygenation characteristics using the desaturation and resaturation time in 47 OSA subjects from the Molecular Signatures of Obstructive Sleep Apnea Cohort (MSOSA). We observe that a cycle of intermittent hypoxia is not sinusoidal; specifically, desaturation time increases in an almost linear relationship to the degree of hypoxia (nadir), whereas resaturation time is somewhat constant (∼15 s), irrespective of the nadir. Second, we modified the Hycon mouse model of CIH to accommodate a 15-s resaturation time. Using this modified CIH model, we explored whether a short resaturation schedule (15 s), which includes the characteristics of OSA patients, had a different effect on levels of oxidative stress (i.e., urinary 8,12- iso-iPF2α-VI levels) compared with sham and a long resaturation schedule (90 s), a schedule that is not uncommon in rodent models of CIH. Results suggest that shorter resaturation time may result in a higher level of 8,12- iso-iPF2α-VI compared with long resaturation or sham conditions. Therefore, simulating the rodent model of CIH to reflect this and other OSA patients' oxygenation characteristics may be worthy of consideration to better understand the effects of hypoxia, oxidative stress, and their interactions.

scholarly journals Curcumin prevents chronic intermittent hypoxia-induced myocardial injury

2020 ◽  
Vol 11 ◽  
pp. 204062232092210 ◽  
Author(s):  
Sophie Moulin ◽  
Claire Arnaud ◽  
Sophie Bouyon ◽  
Jean-Louis Pépin ◽  
Diane Godin-Ribuot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Er Stress ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Sleep Apnoea ◽  
Cardiac Response ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep

Background: Chronic intermittent hypoxia (IH), the hallmark feature of obstructive sleep apnoea syndrome, contributes to infarct size enhancement after myocardial ischemia–reperfusion (I/R). Curcumin (Curc), the natural pigment of Curcuma longa, has been demonstrated to be beneficial in the context of myocardial injury. In this study, we assessed the effects of Curc on the maladaptive cardiac response to IH, and particularly on IH-induced hypoxia inducible factor-1 (HIF-1) expression, oxidative stress, inflammation, endoplasmic reticulum (ER) stress and apoptosis. Methods: Swiss/SV129 mice were exposed to normoxia or IH (21–5% FiO2, 60 s cycles, 8 h per day, for 21 days) and treated orally with Curc (100 mg kg−1 day−1, oral gavage) or its vehicle. Mice were then either euthanised for heart sampling in order to perform biochemical and histological analysis, or subjected to an in vivo ischemia-reperfusion protocol in order to measure infarct size. Results: IH increased nuclear HIF-1α expression and superoxide anion (O2.–) production as well as nuclear factor kappa B (NF-kB) p65, glucose-regulated protein (Grp78) and C/EBP homologous protein (CHOP) expression. IH also induced apoptosis and increased infarct size after I/R . The IH-induced HIF-1 activation, oxidative stress, inflammation, ER stress and apoptosis were abolished by chronic Curc treatment. Curc also significantly decreased infarct size only in mice exposed to IH. Conclusion: Curc prevents IH-induced myocardial cell death signalling. Curc might be used as a combined therapy with continuous positive airway pressure in sleep apnoea patients with high cardiovascular risk.

scholarly journals Edaravone mitigates cognitive impairment and hippocampal injury in juvenile rats with obstructive sleep apnea hypopnea syndrome via regulation of cAMP/PKACREB pathway

2021 ◽  
Vol 20 (11) ◽  
pp. 2299-2304
Author(s):  
Yongmei Zhao ◽  
Hongli Li ◽  
Yong Chen ◽  
Kexing Li ◽  
Sufei Yang
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Cognitive Impairment ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
New Drugs ◽  
Juvenile Rats ◽  
Protein Levels ◽  
Obstructive Sleep ◽  
Hypopnea Syndrome

Purpose: To investigate the influence of edaravone on cognitive impairment and hippocampal injury in juvenile rats with obstructive sleep apnea hypopnea syndrome (OSAHS), and the mechanism involved.Methods: Fifty-four young Wistar rats were randomly selected into control, intermittent hypoxia and edaravone groups. The contents of the antioxidants CAT, Mn-SOD, Cu/Zn SOD and oxidative stress products malondialdehyde (MDA) in hippocampus were assayed and compared. The expressions of brain-derived neurotrophic factor (BDNF), Bcl-2, CREB, p-CREB and PKAc were determined.Results: The times taken to cross the target quadrant and the platform; levels of CAT and Mn-SOD, as well as protein levels of BNDF, Bcl-2, p-CREB and PKAc were markedly lower in intermittent hypoxia group than in controls; and MDA contents, 8-OHdG and protein hydroxyl were markedly higher in intermittent hypoxic rats group than in controls. Time taken to cross the platform and quadrant; activities of CAT and Mn-SOD, and protein concentrations of BDNF, Bcl-2, p-CREB and PKAc were markedly higher in the edaravone-treated rats than in intermittent hypoxia rats.Conclusion: Edaravone significantly mitigated cognitive damage and hippocampal lesions in OSAHS rats via a mechanism related to alleviation of oxidative stress and up-regulation of the expressions of p-CREB and its downstream proteins BDNF and Bcl-2. This finding provides a theoretical basis for research and development of new drugs against OSAHS.

Chronic intermittent hypoxia increases infarction in the isolated rat heart

2005 ◽  
Vol 98 (5) ◽  
pp. 1691-1696 ◽  
Author(s):  
M. Joyeux-Faure ◽  
F. Stanke-Labesque ◽  
B. Lefebvre ◽  
P. Béguin ◽  
D. Godin-Ribuot ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Obstructive Sleep Apnea ◽  
Heart Disease ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Vascular Reactivity ◽  
Carotid Arteries ◽  
Ischemia Reperfusion ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep

Coronary heart disease is frequently associated with obstructive sleep apnea syndrome and treating obstructive sleep apnea appears to significantly improve the outcome in coronary heart disease. Thus we have developed a rat model of chronic intermittent hypoxia (IH) to study the influence of this condition on myocardial ischemia-reperfusion tolerance and on functional vascular reactivity. Wistar male rats were divided in three experimental groups ( n = 12 each) subjected to chronic IH (IH group), normoxia (N group), or control conditions (control group). IH consisted of repetitive cycles of 1 min (40 s with inspired O2 fraction 5% followed by 20 s normoxia) and was applied for 8 h during daytime, for 35 days. Normoxic cycles were applied in the same conditions, inspired O2 fraction remaining constant at 21%. On day 36, mean arterial blood pressure (MABP) was measured before isolated hearts were submitted to an ischemia-reperfusion protocol. The thoracic aorta and left carotid artery were also excised for functional reactivity studies. MABP was not significantly different between the three experimental groups. Infarct sizes (in percent of ventricles) were significantly higher in IH group (46.9 ± 3.6%) compared with N (26.1 ± 2.8%) and control (21.7 ± 2.1%) groups. Vascular smooth muscle function was similar in aorta and carotid arteries from all groups. The endothelium-dependent relaxation in response to acetylcholine was also similar in aorta and carotid arteries from all groups. Chronic IH increased heart sensitivity to infarction, independently of a significant increase in MABP, and did not affect vascular reactivity of aorta and carotid arteries.

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