losartan-potassium and Sleep-Apnea--Obstructive

Intermittent hypoxia stimulates the development of adaptive responses, called preconditioning. This process is partially mediated by genetic remodeling, via hypoxia inducible factor (HIF), which induces long-term adaptation processes and is responsible for the increase of levels of vascular endothelial growth factor (VEGF), erythropoietin (Epo), atrial natriuretic peptide (ANP), and nitric oxide (NO). The synthesis of brain-derived neurotrophic factor (BDNF) participates in the control of neural plasticity after hypoxia. The mechanisms of neuroprotection against hypoxia may be related to vascular adjustments and to central neurogenic neuroprotection. Some of the factors known to be involved in the development of the mechanism of neuroprotection are also present in the responses to repetitive apneas that occur during sleep in patients with obstructive sleep apnea (OSA) syndrome, who are frequently exposed to severe sleep hypoxemia. It appears that OSA syndrome represents a clinical example of preconditioning and the development of adaptive responses to intermittent hypoxia.

Topics: Adaptation, Biological; Animals; Atrial Natriuretic Factor; Brain-Derived Neurotrophic Factor; Erythropoietin; Humans; Nitric Oxide; Sleep Apnea, Obstructive; Vascular Endothelial Growth Factor A

High serum erythropoietin (EPO) levels have been reported in adult patients with obstructive sleep apnea (OSA), however there is a lack of related literature in children with OSA. The main objective of this study was to explore the potential use of EPO as a pediatric OSA biomarker by exploring the relationship between serum EPO levels and the presence of pediatric OSA.. A prospective study was conducted on children (4-12 years old) referred for overnight PSG. Thirty (30) consecutive children with mild. 30 consecutives with moderate, and 30 consecutives with severe OSA (OSA group), as well as 30 consecutive children with AHI≤1 (non-OSA group) were recruited. Morning blood specimens after PSG studies were obtained in order to compare EPO levels.. Finally, 115 children included for analysis. Non-OSA group consisted of 29 children (mean age: 6.93 ± 2.10) and OSA-group of 86 children (mean age: 6.78 ± 2.53). Mean EPO values for the non-OSA and OSA groups were 5.46 ± 2.29 mIU/ml and 8.33 ± 4.10 mIU/ml respectively. OSA-group had significant higher EPO levels than non-OSA (P: 0.01) while EPO levels were significantly correlated with AHI (p < 0.001).. Our study showed that serum EPO levels of children with OSA are significantly higher than those without OSA and correlate significantly with AHI. These results suggest that EPO may be considered as a biomarker candidate for pediatric OSA. Since this may be the first study on the topic further research is needed.

Topics: Biomarkers; Child; Child, Preschool; Erythropoietin; Humans; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive

The aim of this study was to investigate the effects of mandibular advancement device (MAD) therapy for obstructive sleep apnea-hypopnea syndrome (OSAHS) on hypoxia-inducible factor-1α (HIF-1α), erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in myocardial tissue. New Zealand rabbits were used to develop OSAHS and MAD models. Cone beam computed tomography (CBCT) of the upper airway and polysomnography (PSG) recordings were performed with the animals in the supine position. All of the animals were induced to sleep in a supine position for 4-6 h each day and were observed continuously for 8 weeks. The myocardial tissue of the three groups was dissected to measure the expression of HIF-1α, EPO and VEGF. The results showed that there was higher expression of HIF-1α, EPO and VEGF in the OSAHS group than those in the MAD and control groups. MAD treatment significantly downregulated the expression of HIF-1α, EPO and VEGF in the OSAHS animals. We concluded that MAD treatment could significantly downregulate the increased expression of HIF-1α, EPO and VEGF in OSAHS rabbits, improving their myocardial function.

Topics: Animals; Case-Control Studies; Cone-Beam Computed Tomography; Disease Models, Animal; Erythropoietin; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Myocardium; Occlusal Splints; Polysomnography; Rabbits; Sleep Apnea, Obstructive; Up-Regulation; Vascular Endothelial Growth Factor A

A high level of endogenous erythropoietin (EPO) may be associated with a smaller infarct size determined by the release of necrosis markers. Sleep-disordered breathing (SDB) is a well-known risk factor for cardiovascular diseases. In contrast, protective effects of SDB have also been described. The potential role of increased levels of EPO and vascular endothelial growth factor (VEGF) is suggested in this process. The study aimed to explore the EPO and VEGF serum levels in SDB and non-SDB patients during the acute phase of myocardial infarction.. Thirty-seven patients undergoing successful primary percutaneous coronary intervention in the acute myocardial infarction have been examined for the levels of EPO, VEGF, and troponin I (Tn). In the following, patients had an overnight polysomnography to determine breathing disturbances during sleep.. Both on admission day (day 1) and day 3 of hospitalization, EPO levels showed statistically significant differences in both SDB-positive and SDB-negative patient groups (p = 0.003 and p = 0.018, respectively). There was no statistically significant difference in VEGF levels. No correlation was found between the EPO and Tn levels.. SDB patients tend to have higher levels of EPO during acute myocardial infarction. No statistically significant differences in VEGF levels were observed.

Topics: Erythropoietin; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Polysomnography; Sleep Apnea, Obstructive; Statistics as Topic; Troponin I; Vascular Endothelial Growth Factor A

Both anemia and sleep disordered breathing are common in patients with dialysis-dependent stage 5 chronic kidney disease. Erythrocytosis resulting from obstructive sleep apnea (OSA) is rare in the general population and has never been described in the hemodialysis population. We present a case of asymptomatic isolated erythrocytosis and elevated serum erythropoietin level in an otherwise well and previously erythropoietin-dependent chronic hemodialysis patient with chronic kidney disease secondary to ischemic nephropathy. There was no history or symptoms of cardio-pulmonary or hepatic diseases nor any relevant family history. Screening work-up for malignancies was negative. The clinical history was highly suggestive of OSA and severe OSA (respiratory disturbance index of 59) was confirmed by polysomnographic studies. Successful treatment of the OSA with continuous positive airway pressure resulted in permanent stabilization of the hemoglobin to levels below 13 g/dL without the need for repeated phlebotomies and in dramatic lowering of serum erythropoietin levels. To our knowledge, this is the first case of OSA mediated erythrocytosis in a dialysis patient documented in the literature.

Topics: Erythropoietin; Humans; Kidney Failure, Chronic; Male; Middle Aged; Phlebotomy; Polycythemia; Polysomnography; Renal Dialysis; Sleep Apnea, Obstructive

To investigate the effect of uvulopalatopharyngoplasty on change of serum erythropoietin levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) treatment.. Fifty-nine patients with OSAHS were treated through uvulopalatopharyngoplasty. Observing follow indexes of pre and postoperation: pharyngeal space, neck size. Pre and post-operative serum erythropoietin levels were detected.. Neck size, AHI, BMI, SaO2, distance between anterior pillars, distance between uvula and posterior wall, length of palatum, length of uvula and minimum sekar of pharynx oralis in preoperative patients were significant higher than those in postoperative patients (P<0.01). Neck size, BMI and minimum sekar of pharynx oralis in postoperative patients were significant higher than those in normal adults (P<0.01). There were no significant difference between postoperative patients and normal adults in distance between anterior pillars, distance between uvula and posterior wall, length of palatum, length of uvula (P>0.01). The level of EPO in preoperative patients were significant higher than that in postoperative patients (P<0.01). There was no significant difference between postoperative patients and normal adults in the level of EPO (P>0.01).. The level of EPO in OSAHS patients is higher than that in normal adults. It was correlative with AHI. The uvulopalatopharyngoplasty was efficacious in treatment of OSAHS. The levels of EPO were decreased through efficacious treatment.

Topics: Adult; Aged; Erythropoietin; Female; Humans; Male; Middle Aged; Palate; Pharynx; Sleep Apnea, Obstructive; Uvula; Young Adult

The short, repetitive hypoxaemic episodes observed in obstructive sleep apnoea (OSA) may determine small augmentations in mature red blood cells. It is unknown whether they affect reticulocyte release. This study explored whether the number and degree of maturation of circulating reticulocytes may be altered in OSA, possibly through the effect of erythropoietin.. Fifty male adult patients with suspected OSA, normoxic during wakefulness, were studied. After nocturnal polysomnography, a blood sample was withdrawn for blood cells count, erythropoietin, iron and transferrin determination. Reticulocyte concentration and degree of immaturity [high (H), medium (M), or low (L)] were also determined. Immature reticulocyte fraction (IRF) was calculated as (M+H) percentage of reticulocytes.. A wide range of OSA severity was found [apnoea/hypopnoea index (AHI): 44.3 +/- 30.4, range 0.3-105; sleep time spent at oxyhaemoglobin saturation <90%: 18.1 +/- 22.2%, range 0-81%]. Both reticulocyte count and IRF slightly exceeded the normal range. Patients with a reticulocyte concentration > 2% had higher EPO levels (p < 0.05), but not worse nocturnal desaturations, than those with values < 2%. By contrast, subjects with IRF < 15% showed worse desaturations (p < 0.05), but similar EPO concentrations, when compared to subjects whose IRF was < 10%. At univariate analysis, reticulocyte count correlated to erythropoietin, while IRF to transferrin saturation, BMI and OSA severity. At multiple regression, only lowest nocturnal oxygen saturation remained a significant contributor to IRF (r2 0.223, p < 0.05).. This data suggests that hypoxaemia due to OSA could influence the release of immature reticulocytes, but this effect is not mediated by erythropoietin.

Topics: Adult; Cohort Studies; Erythropoiesis; Erythropoietin; Humans; Male; Middle Aged; Polysomnography; Reticulocyte Count; Severity of Illness Index; Sleep Apnea, Obstructive; Transferrin

As a noninvasive method, exhaled breath condensate (EBC) has gained importance to improve monitoring of lung diseases and to detect biomarkers. The aim of the study was to investigate, whether erythropoietin (EPO) is detectable in EBC. EBC was collected from 22 consecutive patients as well as from healthy individuals. Using a multiplex fluorescent bead immunoassay, we detected EPO in EBC, as well as tumour necrosis factor-alpha (TNF-alpha) in 13 out of 22 patients simultaneously (EPO 0.21 +/- 0.03 in U/mL and TNF-alpha 34.6 +/- 4.2 in pg/mL, mean +/- SEM). No significant differences for EPO levels or correlation between EPO and TNF-alpha were found but TNF-alpha was significantly higher in patients with chronic obstructive pulmonary disease (COPD) than in non-COPD (obstructive sleep apnoea, OSA, and lung healthy patients). This is the first report of detection of EPO in EBC. Due to the small study size more data is needed to clarify the role of EPO in EBC.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Breath Tests; Case-Control Studies; Erythropoietin; Exhalation; Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

We tested the hypothesis that repetitive severe hypoxemia resulting from obstructive sleep apnea would increase serum erythropoietin, and that this increase would be attenuated by effective treatment of obstructive sleep apnea.. We studied healthy untreated patients with obstructive sleep apnea (18 severe and 10 very mild) before and after acute treatment with continuous positive airway pressure, and 12 healthy control subjects free of obstructive sleep apnea.. Baseline erythropoietin levels before sleep were similar in the obstructive sleep apnea and control groups. However, erythropoietin levels increased (by 20%, P =.037) in patients with severe obstructive sleep apnea after 3.5 hours untreated (lowest O2, 77% +/- 3%), and decreased after 4 hours of continuous positive airway pressure treatment (P =.001). Erythropoietin responses in patients with severe obstructive sleep apnea were different (F = 4.0, P =.03) from controls, in whom erythropoietin levels remained stable throughout the night (P =.94). Erythropoietin responses were similar in very mild obstructive sleep apnea and controls (P =.58).. Our results indicate that untreated severe obstructive sleep apnea results in increased erythropoietin, which decreases after continuous positive airway pressure treatment. Increased erythropoietin may be a potential reversible mechanism to explain the association between obstructive sleep apnea and cardiovascular disease.

Topics: Adult; Cardiovascular Diseases; Continuous Positive Airway Pressure; Erythropoietin; Female; Humans; Hypoxia; Male; Middle Aged; Severity of Illness Index; Sleep Apnea, Obstructive

Topics: Adult; Circadian Rhythm; Erythropoietin; Humans; Hypercapnia; Hyperoxia; Hypoventilation; Hypoxia; Male; Middle Aged; Sleep Apnea, Obstructive; Syndrome

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality; however, some patients with OSA do not develop cardiovascular disease even in the presence of severe nocturnal oxygen desaturations. Vascular endothelial growth factor (VEGF) is a hypoxia-sensitive glycoprotein stimulating neoangiogenesis. We hypothesized that VEGF production is increased in OSA because of repetitive nocturnal hypoxia. Three different groups were investigated: 10 OSA patients with severe nighttime hypoxia (Group A), 10 OSA patients with moderate hypoxia (Group B), and 10 healthy volunteers (Group C). Serum levels of VEGF were measured by ELISA from peripheral venous blood samples obtained at 7 AM. Group A had significantly (p < 0.01) increased VEGF serum levels when compared with Group B and Group C (mean +/- SEM: 410 +/- 77 pg/ml versus 224 +/- 38 pg/ml and 245 +/- 61 pg/ml). The degree of nocturnal oxygen desaturation in OSA significantly correlated with the VEGF concentrations (r = 0.67, p < 0.01). In conclusion, serum levels of VEGF are elevated in severely hypoxic patients with OSA and are related to the degree of nocturnal oxygen desaturation. This might constitute an adaptive mechanism to counterbalance the emergence of OSA-related cardiovascular disease.

Topics: Adaptation, Physiological; Analysis of Variance; Case-Control Studies; DNA-Binding Proteins; Endothelial Growth Factors; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Forced Expiratory Volume; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Logistic Models; Lymphokines; Male; Nuclear Proteins; Obesity; Oximetry; Oxygen; Polysomnography; Recurrence; Severity of Illness Index; Sleep Apnea, Obstructive; Transcription Factors; Up-Regulation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vital Capacity

To better understand how humans adapt to hypoxia, the levels of hemoglobin (Hb), serum erythropoietin (Epo), and vascular endothelial growth factor (VEGF) were measured in 106 patients with severe obstructive sleep apnea-hypopnea syndrome. The results indicated that temporal hypoxic stimulation increases Hb. Furthermore, a minor increase in Epo and a substantial increase in VEGF were found. The induction in patients with severe sleep apnea was greater than that reported in other types of hypoxia. (Blood. 2001;98:1255-1257)

Topics: Case-Control Studies; Endothelial Growth Factors; Erythropoietin; Hemoglobins; Humans; Hypoxia; Lymphokines; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Syndrome; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors