OBJECTIVE: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA. METHODS: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), and percentage of time with SpO2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively. RESULTS: The [HCO3-] level was normal in most patients (average 24.0 ± 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030, <0.001, <0.001, and <0.001, respectively). [HCO3-] was independently associated with ODI, mean SpO2, minimum SpO2, and T90% after adjusting for confounders (β value [95%CI]: 1.21 [0.88-1.54], -0.16 [-0.20 to -0.11], -0.51 [-0.64 to -0.37], 1.76 [1.48-2.04], respectively, all p < 0.001). 1 mmol/L elevation of [HCO3-] was associated with a 4% increased odds of uncontrolled hypertension (OR: 1.04 [1.01-1.08], p = 0.013). CONCLUSION: We first demonstrated an independent association between [HCO3-] and nocturnal hypoxic burden as well as uncontrolled hypertension in OSA patients. Bicarbonate levels as an adjunctive measure provide insight into the pathophysiology of hypertension in OSA.
- Klíčová slova
- Acid base balance, Biomarker, Blood pressure, Chemosensitivity, Endotype, Precision medicine,
- MeSH
- hydrogenuhličitany MeSH
- hypertenze * epidemiologie komplikace MeSH
- hypoxie komplikace MeSH
- kyslík MeSH
- lidé MeSH
- obstrukční spánková apnoe * MeSH
- průřezové studie MeSH
- syndromy spánkové apnoe * komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- hydrogenuhličitany MeSH
- kyslík MeSH
Pulmonary hypertension is a group of disorders characterized by elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. To test our hypothesis that combining two drugs useful in experimental pulmonary hypertension, statins and dehydroepiandrosterone sulfate (DHEA S), is more effective than either agent alone, we induced pulmonary hypertension in adult male rats by exposing them to hypoxia (10%O2) for 3 weeks. We treated them with simvastatin (60 mg/l) and DHEA S (100 mg/l) in drinking water, either alone or in combination. Both simvastatin and DHEA S reduced mPAP (froma mean±s.d. of 34.4±4.4 to 27.6±5.9 and 26.7±4.8 mmHg, respectively), yet their combination was not more effective (26.7±7.9 mmHg). Differences in the degree of oxidative stress (indicated by malondialdehydeplasma concentration),the rate of superoxide production (electron paramagnetic resonance), or blood nitric oxide levels (chemiluminescence) did not explain the lack of additivity of the effect of DHEA S and simvastatin on pulmonary hypertension. We propose that the main mechanism of both drugs on pulmonary hypertension could be their inhibitory effect on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, which could explain their lack of additivity.
- MeSH
- arteria pulmonalis MeSH
- dehydroepiandrosteron farmakologie terapeutické užití MeSH
- dehydroepiandrosteronsulfát MeSH
- hypoxie komplikace farmakoterapie patologie MeSH
- krysa rodu Rattus MeSH
- plicní hypertenze * farmakoterapie MeSH
- simvastatin farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dehydroepiandrosteron MeSH
- dehydroepiandrosteronsulfát MeSH
- simvastatin MeSH
BACKGROUND: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients' outcome. METHODS: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. RESULTS: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93-1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95-1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). CONCLUSIONS: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. TRIAL REGISTRATION: clinicaltrials.gov NCT02908308 , Registered September 20, 2016.
- Klíčová slova
- Cardiac arrest, Hyperoxemia, Hypoxemia, Mortality, Neurological outcome,
- MeSH
- hypotermie * komplikace MeSH
- hypoxie komplikace MeSH
- kyslík MeSH
- lidé středního věku MeSH
- lidé MeSH
- parciální tlak MeSH
- senioři MeSH
- zástava srdce mimo nemocnici * komplikace MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- kyslík MeSH
Perinatal hypoxic-ischemic insult (HII) is one of the main devastating causes of morbidity and mortality in newborns. HII induces brain injury which evolves to neurological sequelae later in life. Hypothermia is the only therapeutic approach available capable of diminishing brain impairment after HII. Finding a novel therapeutic method to reduce the severity of brain injury and its consequences is critical in neonatology. The present paper aimed to evaluate the effect of sulforaphane (SFN) pre-treatment on glucose metabolism, neurodegeneration, and functional outcome at the acute, sub-acute, and sub-chronic time intervals in the experimental model of perinatal hypoxic-ischemic insult in rats. To estimate the effect of SFN on brain glucose uptake we have performed 18F-deoxyglucose (FDG) microCT/PET. The activity of FDG was determined in the hippocampus and sensorimotor cortex. Neurodegeneration was assessed by histological analysis of Nissl-stained brain sections. To investigate functional outcomes a battery of behavioral tests was employed. We have shown that although SFN possesses a protective effect on glucose uptake in the ischemic hippocampus 24 h and 1 week after HII, no effect has been observed in the motor cortex. We have further shown that the ischemic hippocampal formation tends to be thinner in HIE and SFN treatment tends to reverse this pattern. We have observed subtle chronic movement deficit after HII detected by ladder rung walking test with no protective effect of SFN. SFN should be thus considered as a potent neuroprotective drug with the capability to interfere with pathophysiological processes triggered by perinatal hypoxic-ischemic insult.
- MeSH
- fluorodeoxyglukosa F18 terapeutické užití MeSH
- glukosa MeSH
- hypoxie komplikace MeSH
- isothiokyanatany MeSH
- krysa rodu Rattus MeSH
- mozek diagnostické zobrazování patologie MeSH
- mozková hypoxie a ischemie * diagnostické zobrazování farmakoterapie MeSH
- novorozená zvířata MeSH
- poranění mozku * MeSH
- sulfoxidy MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fluorodeoxyglukosa F18 MeSH
- glukosa MeSH
- isothiokyanatany MeSH
- sulforaphane MeSH Prohlížeč
- sulfoxidy MeSH
Our aim was to study the expression of hypoxia-related proteins as a possible regulatory pathway in the contracted side tissue of relapsed clubfoot. We compared the expression of hypoxia-related proteins in the tissue of the contracted (medial) side of relapsed clubfoot, and in the tissue of the non-contracted (lateral) side of relapsed clubfoot. Tissue samples from ten patients were analyzed by immunohistochemistry and image analysis, Real-time PCR and Mass Spectrometry to evaluate the differences in protein composition and gene expression. We found a significant increase in the levels of smooth muscle actin, transforming growth factor-beta, hypoxia-inducible factor 1 alpha, lysyl oxidase, lysyl oxidase-like 2, tenascin C, matrix metalloproteinase-2, matrix metalloproteinase-9, fibronectin, collagen types III and VI, hemoglobin subunit alpha and hemoglobin subunit beta, and an overexpression of ACTA2, FN1, TGFB1, HIF1A and MMP2 genes in the contracted medial side tissue of clubfoot. In the affected tissue, we have identified an increase in the level of hypoxia-related proteins, together with an overexpression of corresponding genes. Our results suggest that the hypoxia-associated pathway is potentially a factor contributing to the etiology of clubfoot relapses, as it stimulates both angioproliferation and fibroproliferation, which are considered to be key factors in the progression and development of relapses.
- MeSH
- hemoglobin - podjednotky MeSH
- hypoxie komplikace genetika MeSH
- lidé MeSH
- matrixová metaloproteinasa 2 genetika MeSH
- pes equinovarus * genetika MeSH
- recidiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- hemoglobin - podjednotky MeSH
- matrixová metaloproteinasa 2 MeSH
BACKGROUND AND PURPOSE: An accurate determination of the cardioembolic risk in patients with atrial fibrillation (AF) is crucial to prevent consequences like stroke. Obstructive sleep apnea (OSA) is a known risk factor for both AF and stroke. We aim to explore a possible association between OSA and an increased cardioembolic risk in patients with AF. METHODS: We assessed data from the ESADA (European Sleep Apnea Database) cohort where patients with known AF and OSA were included. Parameters of OSA severity and related hypoxia like lowest Spo2 and 4% oxygen desaturation index were analyzed. Patients were stratified according to their cardioembolic risk estimated with the CHA2DS2-VASc score. RESULTS: From the initial cohort of 14 646 patients, a final set of 363 patients were included in the analysis. Indices of hypoxia during sleep were associated with increased CHA2DS2-VASc score (4% oxygen desaturation index 17.9 versus 29.6 versus 30.5 events/hour and the lowest Spo2 81.2 versus 77.8 versus 77.5% for low, moderate, and high cardioembolic risk, respectively, P<0.05). CONCLUSIONS: These results support the potential role of OSA-related hypoxia in the risk for cardioembolic complications such as stroke in patients with AF.
- Klíčová slova
- atrial fibrillation, embolism, hypoxia, risk factor, sleep apnea,
- MeSH
- databáze faktografické MeSH
- embolie epidemiologie MeSH
- fibrilace síní komplikace MeSH
- hodnocení rizik MeSH
- hypoxie komplikace MeSH
- kohortové studie MeSH
- kyslík krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci srdce epidemiologie MeSH
- obstrukční spánková apnoe komplikace epidemiologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kyslík MeSH
Neonatal hypoxic-ischemic encephalopathy is a disorder with heterogeneous manifestation due to asphyxia during perinatal period. It affects approximately 3-12 children per 1000 live births and cause death of 1 million neonates worldwide per year. Besides, motor disabilities, seizures, impaired muscle tone and epilepsy are few of the consequences of hypoxic-ischemic encephalopathy. Despite an extensive research effort regarding various treatment strategies, therapeutic hypothermia with intensive care unit supportive treatment remains the only approved method for neonates who have suffered from moderate to severe hypoxic-ischemic encephalopathy. However, these protocols are only partially effective given that many infants still suffer from severe brain damage. Thus, further research to systematically test promising neuroprotective treatments in combination with hypothermia is essential. In this review, we discussed the pathophysiology of hypoxic-ischemic encephalopathy and delved into different promising treatment modalities, such as melatonin and erythropoietin. However, preclinical studies and clinical trials are still needed to further elucidate the mechanisms of action of these modalities.
- MeSH
- erythropoetin terapeutické užití MeSH
- hypoxie komplikace farmakoterapie patofyziologie MeSH
- látky tlumící činnost CNS terapeutické užití MeSH
- lidé MeSH
- melatonin terapeutické užití MeSH
- mozková hypoxie a ischemie farmakoterapie etiologie patofyziologie MeSH
- novorozenec MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- erythropoetin MeSH
- látky tlumící činnost CNS MeSH
- melatonin MeSH
Exposure to hypoxia, leading to hypoxic pulmonary hypertension (HPH), is associated with activation of alveolar macrophages (AM). However, it remains unclear how AM participate in this process. There are studies which imply that the AM product monocyte chemoattractant protein-1 (MCP-1) plays an important role. Thus we tested: 1. if the selective elimination of AM attenuates HPH in rats, 2. the correlation of MCP-1 plasmatic concentrations with the presence and absence of AM during exposure to hypoxia, 3. the direct influence of hypoxia on MCP-1 production in isolated AM. We found that experimental depletion of AM attenuated the chronic hypoxia-induced increase in mean pulmonary arterial pressure, but did not affect the serum MCP-1 concentrations. Furthermore, the MCP-1 production by AM in vitro was unaffected by hypoxia. Thus we conclude that AM play a significant role in the mechanism of HPH, but MCP-1 release from these cells is most likely not involved in this process. The increase of MCP-1 accompanying the development of HPH probably originates from other sources than AM.
- MeSH
- alveolární makrofágy metabolismus MeSH
- chemokin CCL2 krev MeSH
- dichlormethylendifosfonát terapeutické užití MeSH
- hypoxie komplikace MeSH
- plicní hypertenze imunologie prevence a kontrola MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Ccl2 protein, rat MeSH Prohlížeč
- chemokin CCL2 MeSH
- dichlormethylendifosfonát MeSH
Despite the urgent need for experimental research in the field of acute heart failure and, particularly cardiogenic shock, currently there are only limited options in large animal models enabling research using devices applied to human subjects. The majority of available models are either associated with an unacceptably high rate of acute mortality or are incapable of developing sufficient severity of acute heart failure. The objective of our research was to develop a novel large animal model of acute severe cardiogenic shock. Advanced left ventricular dysfunction was induced by global myocardial hypoxia by perfusing the upper body (including coronary arteries) with deoxygenated venous blood. The model was tested in 12 pigs: cardiogenic shock with signs of tissue hypoxia developed in all animals with no acute mortality. Cardiac output decreased from a mean (+/- SD) of 6.61+/-1.14 l/min to 2.75+/-0.63 l/min, stroke volume from 79.7+/-9.8 ml to 25.3+/-7.8 ml and left ventricular ejection fraction from 61.2+/-4.3 % to 17.7+/-4.8 % (P
Obstructive sleep apnea (OSA) is associated with insulin resistance, glucose intolerance, and type 2 diabetes. Causal mechanisms mediating this association are not well defined; however, augmented lipolysis in adipose might be involved. Here, we investigated the effect of acipimox treatment (lipolysis inhibitor) on glucose tolerance and insulin sensitivity in mice exposed to intermittent hypoxia (IH). C57BL6/J mice were exposed for 14 days to IH or control conditions. IH was created by decreasing the fraction of inspired oxygen from 20.9 to 6.5%, 60 times/h. Control exposure was air (fraction of inspired oxygen, 20.9%) delivered at an identical flow rate. Acipimox was provided in drinking water (0.5 g/ml) during exposures. After exposures, intraperitoneal insulin (0.5 IU/kg) and glucose (1 g/kg) tolerance tests were performed, and primary adipocytes were isolated for lipolysis experiments. IH elevated fasting glucose by 51% and worsened glucose tolerance and insulin sensitivity by 33 and 102%, respectively. In parallel, IH increased spontaneous lipolysis by 264%, and reduced epididymal fat mass by 15% and adipocyte size by 8%. Acipimox treatment prevented IH-induced lipolysis and increased epididymal fat mass and adipocyte size by 19 and 10%, respectively. Acipimox fully prevented IH-induced impairments in fasting glycemia, glucose tolerance, and insulin sensitivity. For all reported results, P less than 0.05 was considered significant. Augmented lipolysis contributes to insulin resistance and glucose intolerance observed in mice exposed to IH. Acipimox treatment ameliorated the metabolic consequences of IH and might represent a novel treatment option for patients with obstructive sleep apnea.
- Klíčová slova
- diabetes, insulin resistance, intermittent hypoxia, lipolysis, obstructive sleep apnea,
- MeSH
- adipozita účinky léků MeSH
- experimentální diabetes mellitus krev komplikace genetika patologie MeSH
- fenotyp MeSH
- glukosa metabolismus MeSH
- hypoxie komplikace metabolismus MeSH
- inzulin metabolismus MeSH
- lipolýza * účinky léků MeSH
- mastné kyseliny krev MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- obstrukční spánková apnoe krev komplikace genetika patologie MeSH
- pyraziny farmakologie MeSH
- regulace genové exprese účinky léků MeSH
- signální transdukce účinky léků MeSH
- tukové buňky účinky léků patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- acipimox MeSH Prohlížeč
- glukosa MeSH
- inzulin MeSH
- mastné kyseliny MeSH
- pyraziny MeSH
