thromboxane-b2 and Sleep-Apnea--Obstructive

Obstructive sleep apnea increases the risk of cardiovascular diseases. Alternations in prostacyclin and thromboxane concentrations and balance could constitute one of mechanisms linking sleep apnea and cardiovascular events. Thus we aimed to assess the concentrations of 6-keto-prostaglandin F1α (6-keto-PGF1α) (metabolite of prostacyclin) and thromboxane B2 (TXB2) (metabolite of thromboxane A2) in urine and blood of obstructive sleep apnea patients and controls (snoring subjects with otherwise normal polysomnogram).. Overnight urine and morning blood samples were taken from subjects and controls at baseline and in sleep apnea group during continuous positive airway pressure (CPAP) treatment. Samples were analyzed using mass chromatography/gas spectrometry.. We analyzed data from 26 obstructive sleep apnea subjects (mean apnea-hypopnea index 45.4±17.3) and 22 well-matched controls. At baseline sleep apnea patients, when compared to controls, have higher 6-keto-PGF1α in urine (0.89±0.15 vs 0.34±0.06, p=0.01) and blood (24.49±1.54 vs 19.70±1.77, p=0.04). TXB2 levels in urine and blood were not different across groups. CPAP treatment significantly decreased 6-keto-PGF1α in urine (0.92±0.17 vs 0.22±0.10, p=0.04), but not in blood. TXB2 levels during CPAP treatment did not change significantly.. These results suggest augmented systemic prostacyclin production in obstructive sleep apnea patients, which potentially could constitute a protective mechanism against detrimental effects of sleep apnea.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Case-Control Studies; Continuous Positive Airway Pressure; Epoprostenol; Female; Humans; Male; Middle Aged; Sleep Apnea, Obstructive; Thromboxane B2; Thromboxanes

Intermittent hypoxia, the main stimulus of obstructive sleep apnoea (OSA), induces inflammation, leading to early atherosclerosis. Whether the cyclooxygenase (COX) pathway contributes to intermittent hypoxia-induced atherosclerosis remains to be determined. We studied the effects of 8-weeks of intermittent hypoxia exposure on COX-pathway gene expression and atherosclerosis, and the influence of COX-1 inhibition by SC-560 on atherosclerosis progression in aortas of apolipoprotein E(-/-) mice. Urinary 11-dehydrothromboxane B2 (11-dTXB2) was assessed in 50 OSA subjects free of cardiovascular risk factor matched for age and body mass index with 25 controls, and 56 OSA with cardiovascular risk factor. Intermittent hypoxia significantly increased atherosclerotic lesion sizes, mRNA levels of COX-1 and thromboxane synthase (TXBS). Lesion sizes correlated to COX-1 (r = 0.654, p = 0.0003) and TXBS (r = 0.693, p<0.0001) mRNA levels. COX-1 inhibition reduced lesion progression in intermittent hypoxia mice only (p = 0.04). Urinary 11-dTXB2 was similar in OSA subjects free of cardiovascular risk factor and controls, but was increased by 13% (p = 0.007) in OSA subjects with cardiovascular risk factor compared with those without. Although OSA itself was not associated with increased urinary 11-dTXB2 concentration, the COX-1 pathway was activated in intermittent hypoxia-exposed mice and in OSA subjects presenting with cardiovascular risk factor, and may contribute to intermittent hypoxia-induced atherogenesis. COX-1 inhibition could be of clinical interest in the prevention of cardiovascular morbidity in OSA.

Topics: Adult; Animals; Aorta; Apolipoproteins E; Atherosclerosis; Body Mass Index; Body Weight; Case-Control Studies; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Female; Gene Expression Regulation, Enzymologic; Hematocrit; Humans; Hypoxia; Male; Mice; Mice, Transgenic; Middle Aged; Pyrazoles; Risk Factors; Sleep Apnea, Obstructive; Thromboxane B2

Low-grade inflammation may potentially explain the relationship between obstructive sleep apnea syndrome (OSA) and cardiovascular events. However, the respective contribution of intermittent hypoxia and confounders, such as obesity, is still debated.. To monitor urinary leukotriene E(4) (U-LTE(4)), a validated marker of proinflammatory cysteinyl leukotriene production, in OSA; to determine the influence of obesity and other confounders on U-LTE(4) concentrations; to examine the mechanisms involved through transcriptional profiling of the leukotriene pathway in peripheral blood mononuclear cells (PBMCs); and to investigate the effect of continuous positive air pressure (CPAP) on U-LTE(4) concentrations.. We measured U-LTE(4) by liquid chromatography-tandem mass spectrometry.. The U-LTE(4) concentrations were increased (P = .019) in 40 nonobese patients with OSA carefully matched for age, sex, and body mass index (BMI) to 25 control subjects, and correlated (r = 0.0312; P = .017) to the percentage of time spent with mean oxygen saturation (SaO(2)) less than 90%. In a larger cohort of patients with OSA (n = 72), U-LTE(4) increased as a function of BMI (r = 0.445; P = .0002). In those patients, the expression levels of 5-lipoxygenase activating protein mRNA in mononuclear cells exhibited a similar pattern. A stepwise multiple linear regression analysis performed in this cohort identified BMI (P = .001; regression coefficient, 3.33) and percentage of time spent with SaO(2) <90% (P = .001; regression coefficient, 1.01) as independent predictors of U-LTE(4) concentrations. Compared with baseline, CPAP reduced by 22% (P = .006) U-LTE(4) concentrations only in patients with OSA with normal BMI.. Obesity, and to a lesser extent hypoxia severity, are determinant of U-LTE(4) production in patients with OSA.

Topics: 5-Lipoxygenase-Activating Proteins; Adult; Carrier Proteins; Chromatography, Liquid; Female; Humans; Hypoxia; Leukotriene E4; Male; Membrane Proteins; Middle Aged; Obesity; Polysomnography; Prospective Studies; RNA, Messenger; Sleep Apnea, Obstructive; Tandem Mass Spectrometry; Thromboxane B2

To observe the changes of thromboxane B2 (TXB2), rennin, angiotensin II (AT-II), endothelin 1 (ET-1) and anticardiolipin antibody (ACA) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) before and after the operation.. Fifty-four cases of OSAHS confirmed by polysomnography (PSG) were selected as the OSAHS group and 20 normal donors without OSAHS were selected as the control group. Plasma levels of TXB2, rennin, AT- II, ET-1 and ACA were detected by enzyme-linked immunosorbent assay (ELISA).. Plasma levels of TXB2, rennin, AT-II, ET-1 and ACA were higher in patients with OSAHS than those in control group (P < 0.05 or P < 0.01), and the operation therapy decreased them significantly (P < 0.05 or P <0.01). All the plasma parameters were correlated positively with AHI, and negatively with SaO2.. The results indicate the patients with OSAHS were susceptible to thromboembolism disease. Operation therapy is effective in correcting TXB2, rennin, AT-II, ET-1 and ACA.

Topics: Angiotensin II; Antibodies, Antiphospholipid; Case-Control Studies; Chymosin; Endothelin-1; Humans; Sleep Apnea, Obstructive; Thromboxane B2

To observe the changes of thromboxane B(2) (TXB(2)), 6-keto-prostaglandin F1alpha (6-K-PGF1alpha) and anticardiolipin antibody (ACA) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) before and after institution of nasal continuous positive airway pressure (nCPAP).. Sixty cases of OSAHS confirmed by polysomnography (PSG) were selected as the trial group, and 20 normal donors without OSAHS were recruited as the control group. Nineteen patients with severe OSAHS were treated by nCPAP. Plasma levels of TXB(2), 6-K-PGF1alpha were detected by enzyme-linked immunosorbent assay (ELISA).. Plasma (serum) level of TXB(2) (ACA) was significantly higher in patients with moderate to severe OSAHS than that in control group (P < 0.01), and nCPAP therapy decreased its level significantly (P < 0.01). Plasma level of 6-K-PGF1alpha was significantly lower than that in the control group (P < 0.01), and nCPAP therapy increased its level significantly (P < 0.01). TXB(2) and ACA were correlated positively with AHI, and negatively with minimal oxygen saturation (P < 0.01). 6-K-PGF1alpha was correlated negatively with AHI, and positively with minimal oxygen saturation (P < 0.01).. The results indicate that patients with OSAHS are susceptible to thromboembolism disease. TXB(2), 6-K-PGF1alpha, ACA may be associated with the high prevalence of thromboembolism in patients with OSAHS. nCPAP therapy is effective in correcting TXB(2), 6-K-PGF1alpha, ACA.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Antibodies, Anticardiolipin; Continuous Positive Airway Pressure; Female; Humans; Male; Middle Aged; Sleep Apnea, Obstructive; Thromboembolism; Thromboxane B2

To investigate the influence of nasal continual positive airway pressure (nCPAP) on the plasma levels of thromboxane B(2) (TXB(2)), renin, angiotensin II (AT-II), endothelin 1 (ET-1), cyclic AMP (cAMP) and cyclic GMP (cGMP) and evaluate their clinical significance.. 20 patients with OSAS without cardiovascular complications and 20 nromal controls were enrolled in the study, who were monitored with PSG, and then treated with nCPAP during the second night. All the plasma parameters were measured after PSG monitoring and nCPAP management with radio-immunoassay.. Before nCPAP, plasma levels of TXB(2), renin, and AT-II were higher in patients with OSAS than those in control (P < 0.05); Meanwhile, the plasma levels of ET-1, cAMP, and cAMP/cGMP were significantly higher in patients group than those in control (P < 0.01).. Patients with severe OSAS may have disturbances in neuro-regulation and changes in plasma level of TXB(2), renin, AT-II and ET-1, which indicates that the vasoactive substance might be related to the hypoxemia and disturbance in neuro-regulations, and might play an important role in the development of hypertension and other cardiovascular disorders. nCPAP therapy can correct the abnormalities of some vasoactive substances.

Topics: Angiotensin II; Cyclic AMP; Cyclic GMP; Endothelin-1; Positive-Pressure Respiration; Renin; Sleep Apnea, Obstructive; Thromboxane B2