Severity Of Intermittent Hypoxia Research Articles

Intermittent hypoxia by obstructive sleep apnea is significantly associated with electro-anatomical remodeling of the left atrium preceding structural remodeling in patients with atrial fibrillation

BackgroundObstructive sleep apnea (OSA) is one of the risk factors for atrial fibrillation (AF). However, the mechanism underlying the atrial structural and electro-anatomical remodeling by OSA has not yet been clearly elucidated. MethodsThis study was conducted in 83 patients who had undergone catheter ablation for AF (49 with OSA and 34 Controls without OSA). The left atrial (LA) maps were created in all the patients using a three-dimensional electro-anatomical mapping system. The LA with a bipolar voltage of <0.5 mV was defined as the low voltage area (LVA); %LVA was defined as the ratio of the LVA to the total surface area of the LA. ResultsThe LVA and %LVA were significantly greater in the OSA group as compared with the Control group, however, there was no difference in the LA area. The 3 % oxygen desaturation index (ODI) was significantly correlated with the %LVA (r = 0.268, P = 0.014), but not with the LA area. Multiple regression analysis with adjustments identified 3 %ODI ≥30 (3.088, 1.078–8.851, P = 0.036) as being significantly associated with the %LVA. ConclusionsIn patients with AF complicated by OSA, significant increase of the LVA, but not of the LA area, was observed. The intermittent hypoxia severity was significantly associated with the LVA. These results suggest that intermittent hypoxia by OSA might be one of the mechanisms of electro-anatomical remodeling of the LA, possibly preceding structural remodeling represented by LA enlargement, in patients with AF.

0424 Effect of Chronic Intermittent Hypoxia on Global Cerebral Metabolic Rate of Oxygen Consumption in Rats

Abstract Introduction Patients with obstructive sleep apnea (OSA) commonly exhibit grey and white matter loss, which may be related to hypoxic damage in the brain during sleep. Our preliminary data demonstrated lower values of cerebral metabolic rate of oxygen (CMRO2) consumption in apneics versus controls. As such, reduced CMRO2 may be an important contributor to the neurologic consequences of OSA. Here we report a rodent model for chronic intermittent hypoxia (CIH) to quantify effects on CMRO2 consumption. We hypothesized that increased severity of CIH results in decreased CMRO2 levels. Methods Three groups of rats were subject to varying levels of hypoxia: sham (21% oxygen; n = 19), moderate (11% oxygen; n = 14), and severe (6% oxygen; n = 21). To deliver hypoxia, rats were exposed to three-minute cycles of oxygen between 21% and condition-specific nadir O2 for 12 hours daily during their sleep cycle. CMRO2 values were measured with MRI techniques, performed on anesthetized rats before and after 3 months exposure to CIH. Results Rats from the three hypoxia groups did not differ significantly in CMRO2 values at baseline (0 months). After 3 months of exposure to hypoxic conditions, there was a trending difference (p=0.0726) in percent change from baseline between severely hypoxic (-35.3%) and sham (+12.3%) rats. Moderately hypoxic rats demonstrated an intermediate decrease from baseline after 3 months (-19.0%). Conclusion Our findings suggest that increased severity of intermittent hypoxia yields a dose-response decrease in brain oxygen consumption. Our data add to the growing body of evidence on the relationship between obstructive sleep apnea and hypoxic damage in the brain, suggesting that CMRO2 levels may be an indicator of the neurologic consequences of OSA. Support Funded by NIH P01 HL094307

Commentary: Intermittent Hypoxia Severity in Animal Models of Sleep Apnea

Commentary: Intermittent Hypoxia Severity in Animal Models of Sleep Apnea

Intermittent Hypoxia Severity in Animal Models of Sleep Apnea.

Intermittent Hypoxia Severity in Animal Models of Sleep Apnea.

The Relationship between Diabetes-Related Complications and Obstructive Sleep Apnea in Type 2 Diabetes.

This study explored the relationship between obstructive sleep apnea (OSA) and the presence of any diabetes-related complications in type 2 diabetes and whether this was mediated by hypertension. Secondly, the relationship between OSA severity and estimated glomerular filtration rate (eGFR) was investigated. A total of 131 patients participated. OSA was diagnosed using a home monitor, and severity was measured by apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). OSA was found in 75.6% of the participants, 40.5% with moderate-to-severe degree. Any diabetes-related complications (retinopathy, neuropathy, nephropathy, or coronary artery disease) were present in 55.5%, and 70.2% of the participants had hypertension. Mediation analysis indicated that, compared to those with mild or no OSA, those with moderate-to-severe OSA were 3.05 times more likely to have any diabetes-related complications and that this relationship was mediated by the presence of hypertension. After adjusting for confounders, ODI (B = −0.036, p = 0.041), but not AHI, was significantly associated with lower eGFR. In conclusion, moderate-to-severe OSA was related to the presence of any diabetes-related complications in type 2 diabetes, and the relationship was mediated by hypertension. The severity of intermittent hypoxia was associated with lower eGFR. Whether OSA treatment will delay or reduce diabetes-related complications should be investigated.

The Impact of Obstructive Sleep Apnea and Tobacco Smoking on Endothelial Function

Background: Endothelial dysfunction has been recognized to occur in the context of obstructive sleep apnea (OSA) or tobacco smoking. However, the deleterious effect on vascular function with concurrence of both conditions is largely unknown. Objective: To investigate whether the concurrence of OSA and smoking poses an additive detriment to endothelial dysfunction. Methods: Chinese men without a history of chronic medical illness were invited to complete a questionnaire including smoking pack-year exposure, polysomnography and peripheral arterial tonometry (PAT) for endothelial function. Serum 8-isoprostane, advanced oxidation protein products (AOPP) and monocyte chemo-attractant protein-1 (MCP-1) were measured. Results: 114 men were successfully enrolled. PAT ratio, adjusted for age and body mass index, correlated inversely with overall severity of OSA: apnea-hypopnea index (AHI), r = -0.160 (p = 0.092); oxygen desaturation index, r = -0.214 (p = 0.024); duration of oxygen saturation <90%, r = -0.219 (p = 0.020); and minimum oxygen saturation, r = 0.250 (p = 0.008). The PAT ratio decreased with increasing pack-year group (p = 0.018). It was lower with concurrent smoking history and moderate-severe OSA (AHI ≥15/h) compared to having one or neither factor (p = 0.011). Serum levels of 8-isoprostane and AOPP were positively related to severity of OSA, while MCP-1 correlated with smoking quantity. Multiple linear regression analyses showed that severity of intermittent hypoxia, MCP-1 and pack-year exposure were independent predictors of PAT ratio. Conclusion: While OSA, in particular intermittent hypoxemia, and tobacco smoking were independent risk factors, the concurrence of moderate-severe OSA and smoking was associated with the most severe impairment in endothelial function.

Abstract 2174: Increased Platelet Aggregability In Obstructive Sleep Apnea Syndrome Patients Is Improved By Nasal Continuous Positive Airway Pressure Treatment

Background and aim: Obstructive sleep apnea (OSA) is a risk factor for cerebrovascular diseases. One cause for them is an occlusive arterial thrombus triggered by local platelet activation. Whether OSA is an independent risk factor for increased platelet aggregability is unclear. Methods: We enrolled 124 patients with snoring or daytime sleepiness in whom 3% oxygen desaturation index (3%ODI), a principal marker of the severity of intermittent hypoxia and reoxygenation (IHR), was measured. We studied ex vivo ADP- and collagen-induced aggregation of platelet-rich plasma using an optical aggregometer. The agonist concentration giving half maximal aggregation was defined as the platelet-aggregation threshold index (PATI) value. Therefore, the lower PATI value implicates the higher aggregability. In 23 patients who underwent nasal CPAP, platelet aggregability was followed until 90 days. Results: There was a significant difference in the PATI value for ADP-induced aggregation between 66 patients with non-to-mild OSA (3%ODI≤15) (1.04±0.07 μM, mean±SE) and 58 patients with moderate-to-severe OSA(3%ODI&gt;15) (0.78±0.09 μM)(p=0.029). Multiple linear model revealed that 3%ODI strongly significantly contributed to the PATI values for ADP (p&lt;0.001) and collagen (p=0.0026) among the 59 subjects with a cardiovascular risk factor such as smoking, hypertension, diabetes mellitus or hyperlipidemia. However, the percentage of time of arterial O2 saturation&lt;90% during sleep did not significantly contribute to the PATI values for ADP (p=0.21) and collagen (p=0.20). After initiation of nasal CPAP therapy, the PATI values for ADP-induced aggregation significantly worsened transiently on day 30 (p=0.035), and then it recovered and improved at day 90 and the PATI for collagen-induced aggregation improved at day 90 without the transient exacerbation. Conclusions: OSA patients had increased platelet aggregability. Severity of IHR more significantly contributed to platelet aggregation than total hypoxic time. Among OSA patients with conventional cardiovascular risk factors, the effects of IHR on the platelet aggregability was prominent. Nasal CPAP initially induced a transient hyperaggregable state of platelets, after which it continued to improve.

Predictors of elevated tumour necrosis factor level in obstructive sleep apnoea syndrome

Circulating levels of TNF-α are elevated in Obstructive Sleep Apnoea Syndrome (OSAS) and likely contribute to associated cardiovascular diseases. Furthermore, TNF-α has been suggested as a mediator of excessive daytime sleepiness (EDS). We investigated the predictors of TNF-α in OSAS in large, well-selected patient and control cohorts. We undertook a prospective study of 30 non-OSAS (including 22 non-sleepy controls and 8 sleepy non-apnoeic snorers), 36 mild-moderate OSAS and 31 severe OSAS male subjects. All groups were closely matched in age, BMI, smoking status, blood pressure and lipid profile. All subjects were free of other disease and were not taking regular medication. Serum for TNF-α assay was drawn following polysomnography (PSG) in all subjects. 49 patients were commenced on CPAP therapy within one week following PSG; sleep studies and TNF-α measurements were repeated 6 weeks later. TNF-α was higher in OSAS patients than controls (p The severity of intermittent hypoxia is the strongest predictor of TNF-α level supporting a key role of inflammation in the cardiovascular pathophysiology of OSAS. Furthermore, TNF-α is independently associated with EDS.