The Impact of Chronic Intermittent Hypoxia on Cardiac Performance of Patients With Obstructive Sleep Apnea and Cardiovascular Disease

CHEST Journal ◽  
2015 ◽  
Vol 148 (4) ◽  
pp. 1058A
Author(s):  
Faisal Siddiqui ◽  
Madalina Macrea ◽  
Mitchell Horowitz ◽  
Thomas Martin ◽  
Tomer Pelleg ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Cardiac Performance ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep ◽  
The Impact

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.

Cardiovascular outcomes of CPAP therapy in obstructive sleep apnea syndrome

2007 ◽  
Vol 293 (4) ◽  
pp. R1666-R1670 ◽  
Author(s):  
Walter T. McNicholas
Keyword(s):  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Obstructive Sleep Apnea Syndrome ◽  
Sleep Apnea Syndrome ◽  
Cpap Therapy ◽  
Obstructive Sleep ◽  
Cardiovascular Morbidity And Mortality ◽  
Apnea Syndrome ◽  
The Impact

Considerable evidence is now available of an independent association between obstructive sleep apnea syndrome (OSAS) and cardiovascular disease. The association is particularly strong for systemic arterial hypertension, but there is growing evidence of an association with ischemic heart disease and stroke. The mechanisms underlying cardiovascular disease in patients with OSAS are still poorly understood. However, the pathogenesis is likely to be a multifactorial process involving a diverse range of mechanisms, including sympathetic overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation, and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism. Therapy with continuous positive airway pressure (CPAP) has been associated with significant benefits to cardiovascular morbidity and mortality, both in short-term studies addressing specific aspects of morbidity, such as hypertension, and more recently in long-term studies that have evaluated major outcomes of cardiovascular morbidity and mortality. However, there is a clear need for further studies evaluating the impact of CPAP therapy on cardiovascular outcomes. Furthermore, studies on the impact of CPAP therapy have provided useful information concerning the role of basic cell and molecular mechanisms in the pathophysiology of OSAS.

scholarly journals Atrial arrhythmias and autonomic dysfunction in rats exposed to chronic intermittent hypoxia

2018 ◽  
Vol 314 (6) ◽  
pp. H1160-H1168 ◽  
Author(s):  
Sara L. Bober ◽  
John Ciriello ◽  
Douglas L. Jones
Keyword(s):  
Obstructive Sleep Apnea ◽  
Electrical Stimulation ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Receptor Protein ◽  
Chronic Intermittent Hypoxia ◽  
Programmed Electrical Stimulation ◽  
Protein Levels ◽  
Obstructive Sleep ◽  
Atrial Vulnerability

Obstructive sleep apnea, which involves chronic intermittent hypoxia (CIH), is a major risk factor for developing atrial fibrillation (AF). Whether or not CIH alone alters cardiac mechanisms to support AF is unknown. This study investigated the effects of CIH on atrial electrophysiology and arrhythmia vulnerability and evaluated the role of autonomics in CIH promotion of AF. Adult male Sprague-Dawley rats were exposed to 8 h/day of CIH or normoxia for 7 days. After exposure, rats were anesthetized for intracardiac electrophysiological experiments. Atrial effective refractory periods (AERPs) and AF inducibility were determined using programmed electrical stimulation and burst pacing in the absence and presence of autonomic receptor agonists and antagonists. Western blot analysis measured atrial protein expression of muscarinic M2, M3, and β1-adrenergic receptors. Compared with normoxia-exposed control rats, CIH-exposed rats had enhanced AF vulnerability using both programmed electrical stimulation and burst pacing, accompanied by greater AERP responses to carbachol and propranolol, lesser responses to isoproterenol, and higher atrial M2 receptor protein levels. Enhanced atrial vulnerability was accentuated by carbachol and abolished by atropine, indicating that the AF-promoting effects of CIH depended principally on parasympathetic activation. Enhancement of atrial vulnerability and AERP shortening with cholinergic agonists in CIH-exposed rats is consistent with sensitivity to parasympathetic activation. Higher responses to adrenergic receptor blockade in CIH-exposed rats is consistent with sympathetic potentiation. These findings implicate CIH as an important mediator of enhanced AF susceptibility in obstructive sleep apnea and provide novel insights into the underlying mechanisms. NEW & NOTEWORTHY Our study demonstrates, for the first time, that chronic intermittent hypoxia alone enhances vulnerability to atrial arrhythmia induction, which depends principally on parasympathetic activation. Enhanced atrial vulnerability was accompanied by heightened electrophysiological responses of the atrial myocardium to carbachol and isoproterenol, dampened responses to propranolol, and increased atrial M2 receptor protein levels.

scholarly journals Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats

2020 ◽  
Vol 318 (1) ◽  
pp. H34-H48
Author(s):  
Alexandria B. Marciante ◽  
Lei A. Wang ◽  
Joel T. Little ◽  
J. Thomas Cunningham
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Chronic Hypertension ◽  
Pressure Regulation ◽  
Neurogenic Hypertension ◽  
Obstructive Sleep ◽  
Induced Hypertension

Obstructive sleep apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into the waking hours. Chronic intermittent hypoxia (CIH), which models the hypoxemia associated with sleep apnea, is sufficient to cause a sustained increase in blood pressure that involves the central nervous system. The median preoptic nucleus (MnPO) is an integrative forebrain region that contributes to blood pressure regulation and neurogenic hypertension. The MnPO projects to the paraventricular nucleus (PVN), a preautonomic region. We hypothesized that pathway-specific lesions of the projection from the MnPO to the PVN would attenuate the sustained component of chronic intermittent hypoxia-induced hypertension. Adult male Sprague-Dawley rats (250–300 g) were anesthetized with isoflurane and stereotaxically injected bilaterally in the PVN with a retrograde Cre-containing adeno-associated virus (AAV; AAV9.CMV.HI.eGFP-Cre.WPRE.SV40) and injected in the MnPO with caspase-3 (AAV5-flex-taCasp3-TEVp) or control virus (AAV5-hSyn-DIO-mCherry). Three weeks after the injections the rats were exposed to a 7-day intermittent hypoxia protocol. During chronic intermittent hypoxia, controls developed a diurnal hypertension that was blunted in rats with caspase lesions. Brain tissue processed for FosB immunohistochemistry showed decreased staining with caspase-induced lesions of MnPO and downstream autonomic-regulating nuclei. Chronic intermittent hypoxia significantly increased plasma levels of advanced oxidative protein products in controls, but this increase was blocked in caspase-lesioned rats. The results indicate that PVN-projecting MnPO neurons play a significant role in blood pressure regulation in the development of persistent chronic intermittent hypoxia hypertension. NEW & NOTEWORTHY Chronic intermittent hypoxia associated with obstructive sleep apnea increases oxidative stress and leads to chronic hypertension. Sustained hypertension may be mediated by angiotensin II-induced neural plasticity of excitatory median preoptic neurons in the forebrain that project to the paraventricular nucleus of the hypothalamus. Selective caspase lesions of these neurons interrupt the drive for sustained hypertension and cause a reduction in circulating oxidative protein products. This indicates that a functional connection between the forebrain and hypothalamus is necessary to drive diurnal hypertension associated with intermittent hypoxia. These results provide new information about central mechanisms that may contribute to neurogenic hypertension.

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