"Pulmonary vasoconstrictor reactivity following intermittent hypoxia" by Jessica Snow
Sleep apnea (SA) affects as many as 20% of the adult population in the United States. It elicits intermittent hypoxia (IH) and causes pulmonary hypertension (PH), however the mechanisms of this PH have not been well studied. IH has been shown to cause polycythemia, pulmonary vascular remodeling and increases in vasoconstrictor reactivity. CO2 supplementation may be protective in the development of PH, therefore we assessed effects of IH with and without CO2 supplementation on indices of PH and pulmonary vasoconstrictor reactivity. IH with CO2 supplementation resulted in eucapnic IH (E-IH) and the lack of polycythemia or vascular remodeling. However, E-IH caused significant right ventricular hypertrophy and increased pulmonary vasoconstrictor reactivity, which was mediated by vascular smooth muscle (VSM) Ca2+ sensitization. We, therefore, sought to determine the mechanism of this enhanced vasoconstrictor reactivity by assessing vasoconstriction and VSM Ca2+ responses to the endothelium-derivedhttp://digitalrepository.unm.edu/biom_etds/3/
Human ventilatory response to CO2 after 8 h of isocapnic or poikilocapnic hypoxia. - Oxford Neuroscience
During ventilatory acclimatization to hypoxia (VAH), the relationship between ventilation (VE) and end-tidal PCO2 (PETCO2) changes. This study was designed to determine 1) whether these changes can be seen early in VAH and 2) if these changes are present, whether the responses differ between isocapnic and poikilocapnic exposures. Ten healthy volunteers were studied by using three 8-h exposures: 1) isocapnic hypoxia (IH), end-tidal PO2 (PETO2) = 55 Torr and PETCO2 held at the subject's normal prehypoxic value; 2) poikilocapnic hypoxia (PH), PETO2 = 55 Torr; and 3) control (C), air breathing. The VE-PETCO2 relationship was determined in hyperoxia (PETO2 = 200 Torr) before and after the exposures. We found a significant increase in the slopes of VE-PETCO2 relationship after both hypoxic exposures compared with control (IH vs. C, P | 0.01; PH vs. C, P | 0.001; analysis of covariance with pairwise comparisons). This increase was not significantly different between protocols IH and PH. No significant changeshttps://www.neuroscience.ox.ac.uk/publications/113443
Frontiers | Intermittent Hypoxia in Childhood: The Harmful Consequences Versus Potential Benefits of Therapeutic Uses |...
Intermittent hypoxia often occurs in early infancy in both preterm and term infants and especially at 36 to 44 weeks postmenstrual age. These episodes of intermittent hypoxia could result from sleep-disordered breathing or may be temporally unrelated to apnea or bradycardia events. There are numerous reports indicating adverse effects of intermittent hypoxia on development, behavior, academic achievement and cognition in children with sleep apnea syndrome. It remains uncertain the exact causative relationship between the neurocognitive and behavioral morbidities and intermittent hypoxia and/or its associated sleep fragmentation. On the other hand, well-controlled and moderate intermittent hypoxia conditioning/training has been used in sick children for treating their various forms of bronchial asthma, allergic dermatoses, autoimmune thyroiditis, cerebral palsy, and obesity. This review article provides an updated and impartial analysis on the currently available evidence in supporting either side of thehttps://www.frontiersin.org/articles/10.3389/fped.2015.00044/full
Intermittent hypoxia increases arterial blood pressure in humans through a Renin-Angiotensin system-dependent mechanism.
Intermittent hypoxia (IH) is believed to contribute to the pathogenesis of hypertension in obstructive sleep apnea through mechanisms that include activation of the renin-angiotensin system. The objective of this study was to assess the role of the thttp://www.biomedsearch.com/nih/Intermittent-Hypoxia-Increases-Arterial-Blood/20625082.html
Silencing of STIM1 attenuates hypoxia-induced PASMCs proliferation via inhibition of the SOC/Ca2+/NFAT pathway | Respiratory...
Continuous or intermittent hypobaric hypoxia can lead to long-term contraction of the pulmonary artery and structural changes in the pulmonary vascular wall known as hypoxic pulmonary vessel remodelling (HPVR) . HPVR is characterised by thickening of small pulmonary artery wall and muscularizing of pulmonary arteriole, which can result in sustained high pulmonary artery pressure and right ventricular hypertrophy . It has become clear that pulmonary vascular smooth muscle cells (PASMCs) are closely related to the development of pulmonary hypertension, which are regulated by intracellular Ca2+ concentrations and calmodulin (CaM) . The intracellular Ca2+ concentration has also been suggested to regulate gene expression and cellular proliferation [2, 6, 22-25]. Intracellular calcium levels in PASMCs are mainly regulated by extracellular calcium influx and the release of intracellular calcium stores. Chelation of extracellular calcium in human PASMCs can significantly inhibit serum or ...https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-14-2
Intermittent vs continuous hypoxia: effects on ventilation and erythropoiesis in humans.
OBJECTIVE: Recently, we showed that 5 days of normobaric intermittent hypoxia at rest (IH; 2 hours daily at 3,800 m simulated altitude; partial pressure of inspired oxygen 90 torr) can induce an increase in the isocapnic hypoxic ventilatory responsehttp://www.biomedsearch.com/nih/Intermittent-vs-continuous-hypoxia-effects/11055563.html
Effects of intermittent hypoxia on oxidative stress and protein degradation in molluscan mitochondria | Journal of Experimental...
Exposure to H/R results in functional reorganization of the mitochondria in bivalves, which markedly differs in two hypoxia-tolerant species (oysters or clams) and a hypoxia-sensitive species (e.g. scallops) (Ivanina et al., 2016, 2012; Kurochkin et al., 2008). Clams show a notably greater mitochondrial tolerance to H/R stress compared with oysters and especially scallops, as indicated by their ability to upregulate the activity of the ETS and oxidative phosphorylation capacity during hypoxia and subsequent reoxygenation (Ivanina et al., 2016, 2012; Kurochkin et al., 2008). Oysters also showed an upregulation of ETS activity during H/R stress (albeit to a lesser degree than clams), whereas in scallops, H/R stress led to a suppression of the ETS activity, collapse of the oxidative phosphorylation capacity, and a decrease in the mitochondrial membrane potential (Ivanina et al., 2016). Mitochondrial injury during H/R stress is driven by the increased ROS production during oxygen influx combined ...http://jeb.biologists.org/content/219/23/3794
Cardiovascular Consequences of Intermittent Hypoxia in Healthy Subjects - Full Text View - ClinicalTrials.gov
The study is a prospective field evaluation to assess the effects of the chronic Intermittent Hypoxia exposure in 12 healthy humans.. Precisely, the study was designed to :. Set up a new model of Chronic Intermittent Hypoxia (CIH) applied to healthy human. This CIH is mimicking the CIH undergone by patients suffering from Sleep Apnea Syndrome.. Evaluate the cardiovascular effect of CIH. Neuronal and humoral sympathetic control, blood pressure control, vascular resistance.. Evaluate the Sleep quality, the ventilation under exposure and the long terms effect on ventilation control of CIH (central and peripheral chemoreflex).. Investigates the biological aspects of CIH exposure. ...https://clinicaltrials.gov/ct2/show/NCT00746928
Effect of acute hypoxia on the hormonal response to exercise | Garvan Institute of Medical Research
The hormonal responses to submaximal exercise under normoxic and hypoxic conditions were studied in eight fit males, aged 22--28 yr, with mean maximal oxygen uptake of 4.4 +/- 0.7 l/min. Studies were performed in a hypobaric chamber, decompressed to a simulated altitude of 4,550 m (PIO2 = 83 Torr). The subjects exercised for 20 min at 750 kpm/min on a cycle ergometer. Venous blood samples were obtained at rest, during exercise and for 60 min after exercise. Plasma glucose, free fatty acids, lactate, cortisol, and serum growth hormone concentrations all increased more during hypoxic exercise than under normoxic conditions. Serum insulin concentration showed a small decrease under normoxic conditions, but decreased by 50% during hypoxic exercise, and was followed by marked rebound when exercise stopped. These changes suggest that energy substrate-hormone interrelationships are altered by hypoxic exercise, resulting in increased fat mobilization and increased gluconeogenesis.https://www.garvan.org.au/research/publications/180
Strength of pulmonary vascular response to regional alveolar hypoxia. - Semantic Scholar
Regional alveolar hypoxia in the lung induces regional pulmonary vasoconstriction which diverts blood flow from the hypoxic area. However, the predominant determinant of the distribution of perfusion in the normal erect lung is gravity so that more perfusion occurs at the base than at the apex. To determine the strength of the regional alveolar hypoxic response in diverting flow with or against the gravity gradient a divided tracheal cannula was placed in anesthetized dogs and unilateral alveolar hypoxia created by venilating one lung with nitrogen while ventilating the other lung with oxygen to preserve normal systemic oxygentation. Scintigrams of the distribution of perfusion obtained with intravenous 13-N and the MGH positron camera revealed a 34 and 32 per cent decrease in perfusion to the hypoxic lung in the supine and erect positions and a 26 per cent decrease in the decubitus position with the hypoxic lung dependent (P equal to 0.94 from supine shift), indicating nearly equal vasoconstrictionhttps://www.semanticscholar.org/paper/Strength-of-pulmonary-vascular-response-to-regiona-Hales-Ahluwalia/f17f032b69a42baf5f44cb6033430b3f99eceaff
Influence of hypoxic ventilatory response on arterial O2 saturation during maximal exercise in acute hypoxia.
The aim of this study was to evaluate the influence of peripheral chemosensitivity estimated by hypoxic ventilatory response (HVR) on arterial oxygen saturation (SaO2) during maximal exercise in acute hypoxia. A group of 16 healthy men performed maxihttp://www.biomedsearch.com/nih/Influence-hypoxic-ventilatory-response-arterial/8789578.html
Inhibition of microRNA-497 ameliorates anoxia/reoxygenation injury in cardiomyocytes by suppressing cell apoptosis and...
Inhibition of microRNA-497 ameliorates anoxia/reoxygenation injury in cardiomyocytes by suppressing cell apoptosis and enhancing autophagyhttps://www.cyagen.com/cn/zh-cn/community/paper/paper-2015618.html
Hypoxicator - Wikipedia
A hypoxicator is a medical device intended to provide a stimulus for the adaptation of an individual's cardiovascular system by means of breathing reduced oxygen hypoxic air and triggering mechanisms of compensation. The aim of intermittent hypoxic training or hypoxic therapy conducted with such a device is to obtain benefits in physical performance and wellbeing through improved oxygen metabolism. There are several commercial systems available, the most popular being Hypoxico, Inc., who pioneered normobaric hypoxic altitude training systems. Most of these systems have not been cleared for medical applications by the FDA and are used by athletes for altitude training. Advanced hypoxicators have a built-in pulse oximeter used to monitor and in some cases control the temporary reduction of arterial oxygen saturation that results in physiological responses evident at both systemic and cellular levels even after only a few minutes of hypoxia. Hypoxic Training Index (HTi) can be used to measure the ...https://en.wikipedia.org/wiki/Hypoxicator
Animals. Male OFA rats (IFFA Credo; 180-200 g) were housed under constant conditions of temperature (23 ± 1°C) and 12:12-h light-dark cycle. The luminance was 200-220 lux at the ground of the chamber. The animals had free access to food and water.. Long-term exposure to hypoxia. The animals were acclimated to their new environment during 1 wk before exposure to hypoxia. Rats (n = 48) exposed to long-term hypoxia were kept for 14 days in a Plexiglas chamber supplied with 10% O2-90% N2. The gas composition was maintained at 10 ± 0.5% O2and CO2 , 0.1%. The CO2 was eliminated by circulating the gas mixture from the chamber to soda lime while metabolic water contained in expiratory gases was continuously trapped into a chilled tank. Normoxic rats (n = 48) were maintained in the same room in normoxic conditions in a Plexiglas chamber.. Dissection. Circadian time 0 (CT0) was determined as the time of lights-on (6:00 AM). On the 15th day of exposition, 8 normoxic and 8 hypoxic animals were killed ...http://ajpregu.physiology.org/content/277/1/R66
HIF-1α Mediates Tumor Hypoxia to Confer a Perpetual Mesenchymal Phenotype for Malignant Progression | Science Signaling
Although tumor progression involves genetic and epigenetic alterations to normal cellular biology, the underlying mechanisms of these changes remain obscure. Numerous studies have shown that hypoxia-inducible factor 1α (HIF-1α) is overexpressed in many human cancers and up-regulates a host of hypoxia-responsive genes for cancer growth and survival. We recently identified an alternative mechanism of HIF-1α function that induces genetic alterations by suppressing DNA repair. Here, we show that long-term hypoxia, which mimics the tumor microenvironment, drives a perpetual epithelial-mesenchymal transition (EMT) through up-regulation of the zinc finger E-box binding homeobox protein ZEB2, whereas short-term hypoxia induces a reversible EMT that requires the transcription factor Twist1. Moreover, we show that the perpetual EMT driven by chronic hypoxia depends on HIF-1α induction of genetic alterations rather than its canonical transcriptional activator function. These mesenchymal tumor cells not ...http://stke.sciencemag.org/content/4/178/pt4
Injury of ascending reticular activating system associated with delayed post-hypoxic leukoencephalopathy: a case report | BMC...
In the current study, three portions of the ARAS (the dorsal lower ARAS, ventral lower ARAS and upper ARAS) in a patient with impaired consciousness following DPHL caused by CO poisoning were evaluated using DTT. We found that these three portions of the ARAS were injured in both hemispheres: the upper ARAS - decreased neural connectivity to both frontal cortexes, basal forebrains, basal ganglia and thalami, the dorsal lower ARAS - non-reconstruction in the right side and narrowing in the left side and the ventral lower ARAS -non-reconstruction in both sides. We believe that the impaired consciousness in this patient was ascribed to the injury of the three portions of the ARAS.. Many studies have reported abnormality of the white matter including basal ganglia (caudate nucleus, putamen, and globus pallidus) in patients with DPHL using various neuroimaging tools including conventional MRI [5-13]. Neurological manifestations were observed as follows: 1) cognitive impairments - confusion, ...https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-017-0917-z/
Postnatal intermittent hypoxia and developmental programming of hypertension in spontaneously hypertensive rats: the role of...
Obstructive and central apneas during sleep are associated with chronic intermittent hypoxia (CIH) and increased cardiovascular morbidity. Spontaneously hypertensive rats exposed to CIH during postnatal days 4 to 30 develop exaggerated hypertension ahttp://www.biomedsearch.com/nih/Postnatal-intermittent-hypoxia-developmental-programming/18474836.html
As solid tumors grow, regions in the tumor become hypoxic because of increased metabolism, heterogeneous and abnormal vasculature delivering oxygen within the tumor, and greater size. In order for the tumor to continue to grow, it depends on survival mechanisms to overcome this hypoxic state, including up-regulation in glycolysis, invasion and metastasis, and angiogenesis, or the growth of new blood vessels. The hypoxia-inducible factor (HIF) transcription factor complex is a major mediator of the cell's response to a hypoxic state and a tumor's survival mechanism under hypoxia. The complex is composed of the hypoxia-dependent HIF-1α subunit and a constitutively expressed HIF-1α subunit, and it requires the co-activator protein p300 to function. In the presence of oxygen, HIF-1α is rapidly degraded. Under hypoxia, HIF-1α forms a complex with HIF-1α and p300 in the nucleus to up-regulate transcription of pro-survival and angiogenic genes. Targeting this transcription factor complex in tumors ...http://cancerres.aacrjournals.org/content/72/8_Supplement/2331
Identification of cyclooxygenase-2 as a major actor of the transcriptomic adaptation of endothelial and tumor cells to cyclic...
fr] OBJECTIF: hypoxie cycliques dans les tumeurs proviennent de l'hétérogénéité dans le flux de RBC et influence non seulement les cellules tumorales mais également des cellules endothéliales qui tapissent les vaisseaux sanguins tumoraux. Whether pO(2) fluctuations, particularly transient reoxygenation periods, alter the well-known hypoxia-inducible factor (HIF)-dependent gene program is largely unknown. Que Po (2) les fluctuations, en particulier réoxygénation des périodes transitoires, de modifier l'hypoxie bien connue-inducible factor (HIF)-programme des gènes dépendant est largement inconnue. EXPERIMENTAL DESIGN: We compared the transcriptomic profiles of endothelial and tumor cells exposed to cyclic hypoxia versus continuous hypoxia to uncover a possible differential effect on angiogenesis and metastases. EXPERIMENTAL DESIGN: Nous avons comparé les profils transcriptomiques de endothéliales et les cellules tumorales exposées à l'hypoxie cyclique par rapport à l'hypoxie ...https://orbi.uliege.be/handle/2268/41396
HKU Scholars Hub: Intermittent hypoxia improves calcium homeostasis in rat cardiomyocytes and confers cardioprotection against...
Calcium (Ca2+) handling is central to cardiac function and may be involved in the cardioprotection induced by intermittent hypoxia (IH). We hypothesized that IH ameliorates the impaired Ca2+ handling during ischemia/reperfusion (I/R). Male Sprague-Dawley rats were exposed to normobaric IH (10% oxygen, 6 hours/day, 7 days). Isolated perfused hearts from the IH and control (in room air) rats were subjected to 30 minutes ischemia and 2 hours reperfusion. The I/R injuries reflected by lactate dehydrogenase (LDH) activity and infarct size (IS) were significantly reduced in the IH group (LDH: 116.0±20.5 U/ml vs. control 273.2±29.5 U/ml, P < 0.01, n=9 per group; IS: 22.2±2.6 % of risk zone vs. control 31.4±3.1 % of risk zone, P < 0.05, n=8 per group). Spectrofluorometric measurement of cytosolic Ca2+ ([Ca2+]i ) in isolated fura-2- loaded ventricular myocytes showed a decrease in the amplitude of electrically induced [Ca2+]i transients with an elevated diastolic [Ca2+]i level during metabolic ...http://hub.hku.hk/handle/10722/105282
Hypoxia increases transcript levels of enzymes involved | Open-i
Hypoxia increases transcript levels of enzymes involved in heme biosynthesis, iron-associated and SreA-associated processes. Microarray datasets include three bhttps://openi.nlm.nih.gov/detailedresult.php?img=PMC3293747_1471-2164-13-62-9&req=4
Impact of the phosphatidylinositide 3-kinase signaling pathway on the cardioprotection induced by intermittent hypoxia |...
BACKGROUND: Exposure to intermittent hypoxia (IH) may enhance cardiac function and protects heart against ischemia-reperfusion (I/R) injury. To elucidate the underlying mechanisms, we developed a cardioprotective IH model that was characterized at hemodynamic, biochemical and molecular levels. METHODS: Mice were exposed to 4 daily IH cycles (each composed of 2-min at 6-8% O2 followed by 3-min reoxygenation for 5 times) for 14 days, with normoxic mice as controls. Mice were then anesthetized and subdivided in various subgroups for analysis of contractility (pressure-volume loop), morphology, biochemistry or resistance to I/R (30-min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion and measurement of the area at risk and infarct size). In some mice, the phosphatidylinositide 3-kinase (PI3K) inhibitor wortmannin was administered (24 µg/kg ip) 15 min before LAD. RESULTS: We found that IH did not induce myocardial hypertrophy; rather both contractility and ...https://air.unimi.it/handle/2434/233599
Abigail Hielscher, PhD
Hielscher A, Qiu C, Porterfield J, Smith Q, Gerecht S. Hypoxia affects the structure of breast cancer cell-derived matrix to support angiogenic responses of endothelial cells (2013) Journal of Carcinogenesis and Mutagenesis doi: 10.4172/2157-2518.S13-005 ...https://www.pcom.edu/academics/faculty/abigailhi.html
Innate biochemical responses of rabbit renal proximal convoluted (PCT) and straight (PST) segments following in vitro exposure to anoxia or hypoxia were investigated to delineate the mechanisms responsible for segment-selective injury in vivo. After bulk isolation, suspensions (1 mg/ml) enriched in either PCT or PST were preincubated in Dulbecco's modified Eagle's-Ham's F-12 medium for 1 h before being exposed to either 40 min of anoxia (N2) or 120 min of hypoxia (1% O2) and 1 h of recovery under air-CO2 conditions. After recovery from anoxia, the percent of control values for each viability indicator in PCT and PST, respectively, were as follows: O2 consumption (QO2), 30/50; ATP content, 22/49; K+ content, 60/70; and percent lactate dehydrogenase (LDH) release, 66/45. Likewise, following recovery from hypoxia, the percent of control values for PCT and PST, respectively, were as follows: QO2, 50/90; ATP, 16/57; K+, 52/79; LDH, 45/17. These differential ...http://ajprenal.physiology.org/content/259/1/F176