Repetitive Hypoxia Research Articles

O035 Refining the desaturation area-based parameters by investigating different baseline methods

Abstract Introduction Repetitive hypoxia serves as the principal mechanistic bridge between Obstructive Sleep Apnoea and cardiovascular disease (CVD). Desaturation area-based parameters, like Hypoxic Burden (HB) and the Respiratory Event Desaturation Transient Area (REDTA), are promising metrics for predicting CVD mortality. These metrics are not without limitations. HB calculation is complex and noise sensitive, while REDTA may be overly simplistic. We investigated six area-based methods, each with a different choice of sampling window and baseline. Methods The oximetry signals from the Sleep Heart Health Study (SHHS) with CVD mortality outcomes and covariate information was used. The HB method was implemented and denoted as ARE. It uses a record-specific sampling window and event-specific baseline. We extended the experiment to include two additional baseline methods: a record-specific baseline (ARR) and a fixed baseline (ARF). Similarly, REDTA which uses a fixed sampling window and baseline (AFF), was extended to an event-specific baseline (AFE) and a record-specific baseline (AFR). Six desaturation area-based methods were performed in this study. The performance of each parameter in predicting CVD mortality was assessed using an adjusted Cox proportional hazard ratio(HR) analysis. Results ARR and AFR outperformed other methods The HRs were ARR:1.79 (95% CI: 1.00-3.19, p<0.05), and AFR:1.64 (95% CI: 1.16-2.32, p<0.01). Discussion Computational complexity was also considered. AFR was easier to calculate than ARR as it used a fixed sampling window. We believe AFR provides a step towards a novel parameter with easy calculation providing early risk stratification in cardiovascular patients.

Longitudinal effects of early exposure to intermittent hypoxia on autonomic cardiovascular control in very preterm infants

IntroductionCardiorespiratory control is immature in infants born preterm compared to those born at term. Animal studies have shown that repetitive hypoxia associated with periodic breathing can alter autonomic control. We aimed to elucidate if the amount of time spent with apnoea and periodic breathing in the neonatal unit was associated with longitudinal changes in autonomic control assessed using heart rate variability. MethodsTwenty-nine very preterm infants (10 M 19F) were studied during supine daytime sleep on 4 occasions. Study 1: 32–36 weeks post menstrual age (PMA) (n = 29), Study 2: 36–40 weeks PMA (n = 27), Study 3: 3-months corrected age (CA) (n = 20) and Study 4: 6-months CA (n = 26). The percentage total sleep time (%TST) spent having apnoeas in active (AS) and quiet sleep (QS) at each study was calculated. Total power, low frequency (LF, sympathetic + parasympathetic activity) high frequency (HF, parasympathetic activity), and LF/HF (sympathovagal balance) were calculated. Infants were divided into two groups based on the %TST spent with apnoeas above and below the median in AS and QS at Study 1. Data were normalised and compared with two-way ANOVA with Bonferroni post-hoc tests. ResultsWhen apnoeas were included in the analysis, in QS Total power and HF power were higher, and when apnoeas were excluded HF power was higher in QS but lower in AS in the above median group at Study 4. ConclusionThis study provides new evidence that short apnoeas, particularly periodic breathing, which is currently not detected or treated in the neonatal unit can affect autonomic cardiovascular control.

Serpin family E member 1 enhances myometrium contractility by increasing ATP production during labor.

The uterine contraction during labor, a process with repetitive hypoxia and high energy consumption, is essential for successful delivery. However, the molecular mechanism of myometrial contraction regulation is unknown. Serpin family E member 1 (SERPINE1), one of the most upregulated genes in laboring myometrium in both transcriptome and proteome, was highlighted in our previous study. Here, we confirmed SERPINE1 is upregulated in myometrium during labor. Blockade of SERPINE1 using small interfering RNA (siRNA) or inhibitor (Tiplaxtinin) under hypoxic conditions in myocytes or myometrium invitro showed a decrease contractility, which was achieved by regulating ATP production. Chromatin immunoprecipitation (ChIP-seq), Co-immunoprecipitation (Co-IP), and glutathione-S-transferase (GST) pull down explored that the promoter of SERPINE1 is directly activated by hypoxia-inducible factor-1α (HIF-1α) and SERPINE1 interacts with ATP Synthase Peripheral Stalk Subunit F6 (ATP5PF). Together they enhance hypoxia driven myometrial contraction by maintaining ATP production in the key oxidative phosphorylation pathway. The results provide new insight for uterine contraction regulation, and potential novel therapeutic targets for labor management.

O058 Are short central apnoeas in preterm infants really benign? Effects on cardiovascular control.

Abstract Introduction Preterm infants frequently experience respiratory instability in the form of short apnoeas and periodic breathing. Animal studies have shown that repetitive hypoxia associated with periodic breathing can alter autonomic control. We aimed to elucidate if apnoea and periodic breathing were associated with autonomic cardiovascular control, thus exacerbating the consequences of respiratory disturbance longitudinally over the first 6 months after hospital discharge. Methods Preterm infants born between 28-32 weeks gestational age (GA) were studied during supine daytime sleep at 32-36 weeks post menstrual age (PMA) (n=29), 36-40 weeks PMA (n=27), 3-months corrected age (CA) (n=20) and 6-months CA (n=26). The percentage total sleep time (%TST) spent having central apnoeas at each study was calculated. Autonomic control was assessed using heart rate variability in ranges of total power, low frequency (LF, reflecting sympathetic + parasympathetic activity) and high frequency (HF, parasympathetic activity), and LF/HF ratio (sympathovagal balance). Results The amount of time spent with short central apnoeas decreased with increasing postnatal age in both active sleep (AS) and quiet sleep (QS). In both sleep states, total, LF and HF power increased with postnatal age, while LF/HF decreased in AS. In both AS and QS %TST spent with short central apnoeas was negatively correlated with Total, LF and HF power (p<0.001 for all) and positively correlated with LF/HF (p<0.05). Conclusion This study provides new evidence that short apnoeas, particularly periodic breathing, which is currently not detected or treated in the neonatal unit can affect autonomic cardiovascular control.

Autonomic cardiovascular control is altered by intermittent hypoxia in preterm infants.

Preterm infants frequently experience short apnoeas and periodic breathing. Animal studies have shown that repetitive hypoxia associated with periodic breathing can alter autonomic control. We aimed to elucidate if apnoea and periodic breathing were associated with changes in autonomic control assessed using heart rate variability, thus exacerbating the consequences of respiratory disturbance. Forty very preterm infants (15 M/25 F) were studied at 34.3 weeks post-menstrual age with daytime polysomnography. Total power, low frequency (LF, sympathetic+parasympathetic activity) high frequency (HF, parasympathetic activity) and LF/HF (sympathovagal balance) were calculated. Infants were divided into those with above and below the median total sleep time spent with respiratory events: Active sleep (AS) 13%, Quiet sleep (QS) 10%. In AS, including respiratory events, Total power (p < 0.05) and HF power (p < 0.05) were higher in the above median group. During AS excluding respiratory events, Total power (p < 0.05) and HF power (p = 0.061) were higher and LF power (p < 0.01) and LF/HF (p < 0.05) were lower in the above median group. There were no differences in HRV parameters in QS. This study provides new evidence that short apnoeas, particularly periodic breathing, which is currently not detected or treated in the neonatal unit can affect autonomic cardiovascular control.

Maternal repetitive hypoxia prior to mating confers epigenetic resilience to memory impairment in male progeny.

We showed previously in a mouse model of vascular cognitive impairment and dementia involving chronic cerebral hypoperfusion (CCH) that repetitive hypoxic conditioning (RHC) of both parents results in the epigenetic, intergenerational transmission of resilience to recognition memory loss in adult progeny, as assessed by the novel object recognition test. The present study was undertaken in the same model to determine whether RHC treatment of one or both parents is required to confer dementia resilience intergenerationally. We found inherited resilience to 3 months of CCH in males is maternally mediated (p = .006). Statistically, we observed a strong trend for the paternal germline to contribute as well (p = .052). We also found that, in contrast to what is widely observed in males, females display intact recognition memory (p = .001) after 3 months of CCH, revealing a heretofore unidentified sexual dimorphism with respect to cognitive impact during disease progression. Overall, results of our study strongly implicate epigenetic changes in maternal germ cells, induced by our repetitive systemic hypoxic stimulus, contributing to a modified differentiation program capable of establishing a dementia-resilient phenotype in adult male first-generation progeny. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sleep apnea and cardiovascular risk.

Obstructive sleep apnea (OSA) is associated with several cardiovascular risk predictors that have only recently begun to be studied in detail. The strong association between OSA and hypertension, coronary artery disease, congestive heart failure, and sudden cardiac death underscores its significant impact on cardiovascular health. This brief review considers the links between OSA and cardiovascular risk. OSA is an important contributor to endothelial dysfunction and damage, while repetitive hypoxia and hypercarbia contribute to autonomic dysfunction and sympathetic stimulation. In turn, these derangements have deleterious hematologic effects, including hypercoagulability and abnormal platelet aggregability, which are important in the pathogenesis of atherothrombotic disease. The varied deleterious effects of OSA on cardiovascular health stem from a unique 'perfect storm' of hypoxic oxidative stress, autonomic dysregulation, endothelial damage, and inflammation occurring at the microvascular level. Further research may disentangle these multiple etiologic threads and provide a better understanding of the underlying pathophysiological relationship between OSA and cardiovascular disease.

Obstructive sleep apnea and coronary artery disease: An unholy nexus or a holy alliance?

Coronary artery disease (CAD) is a significant cause of morbidity and mortality globally, and hypertension, dyslipidemia, diabetes mellitus, and smoking are major cardiovascular (CV) risk factors. Obstructive sleep apnea (OSA) and CAD share an exciting relationship, and recently, OSA has emerged as a non-traditional CV risk factor. OSA is characterized by episodic sleep state-dependent collapse of the upper airway, resulting in periodic reductions or cessations in ventilation, with consequent hypoxia, hypercapnia, or arousals from sleep. The oxidative stress and vascular inflammation resulting from the nocturnal hypoxia followed by reoxygenation cycles predispose the patients to the development of atherosclerotic cardiovascular disease (CVD). Untreated OSA is associated with long-term health consequences, including CVD, metabolic disorders, cognitive impairment, and depression. Paradoxically, some recent studies have reported that patients with OSA may suffer less severe CAD due to the development of collateral circulation due to repetitive hypoxia experienced due to OSA.

Differential response to hypoxia in leiomyoma and myometrial cells

AimsRecent evidence suggests that repetitive hypoxia occurs during menstrual cycles due to vasoconstriction and myometrial contraction. It is unknown if hypoxia contributes to the development of uterine leiomyoma, the most common tumor of the female reproductive system. This study aims to characterize the response to hypoxia in leiomyoma and myometrial cells; and determine if an aberrant leiomyoma response to hypoxia may contribute to leiomyomatogenesis. Main methodsPrimary and immortalized leiomyoma and myometrial cells were cultured under normoxic and hypoxic conditions. Expression levels of vascular endothelial growth factor-A (VEGF-A), adrenomedullin (ADM), endothelin-1 (ET-1), and hypoxia-inducible factor-1 alpha (HIF-1α) were measured by qRT-PCR, western blotting and ELISA. Cell proliferation was assessed using MTT assay and proliferating-cell-nuclear-antigen (PCNA) expression. KC7F2 (HIF-1α inhibitor) was used to examine the regulating mechanisms. Key findingsAs expected, hypoxia induced HIF-1α expression in both leiomyoma and myometrial cells. However, hypoxia induced VEGF-A, ET-1 and ADM expression and VEGF-A secretion into the culture media in leiomyoma but not myometrial cells. MTT assay and PCNA expression showed that hypoxia induces proliferation in leiomyoma, but not myometrial cells. HIF-1α inhibitor abrogated the hypoxia-induced VEGF-A, ET-1, ADM, and PCNA expression in leiomyoma cells. SignificanceThis study suggests an aberrant leiomyoma cellular response to hypoxia compared to myometrium. This differential response to menstruation-related repetitive hypoxia episodes may lead to selective proliferation of hypoxia-adaptive leiomyoma cells and contribute to leiomyoma growth. Thus, in addition to adding to our understanding of leiomyoma pathobiology, the study proposes angiogenic factors as a potential leiomyoma therapeutic target.

Potential Mechanisms Underlying Hypoxia-Induced Diabetes in a Rodent Model: Implications for COVID-19

Previous studies reported that repetitive hypoxia in rat pups reduces insulin secretion and elevates fasting blood glucose levels; these sequelae persisted for several months. This report describes how episodic hypoxic events elevate a chloride ion exporter, K+-Cl− cotransporter-2 (KCC2), in the plasma membrane of insulin-secreting pancreatic β-cells. We assume that acute diabetic symptoms observed in rat pups with periodic oxygen desaturation could result from a lack of blood insulin levels due to disturbed β-cell function. This acute hypo-insulinemia may result from a disruption in chloride balance in β-cells arising from an imbalanced KCC2-NKCC1 (chloride exporter-importer) density as a consequence of periodic oxygen desaturation. Mechanistically, we postulate that a reduced insulin secretion due to the KCC2-NKCC1 imbalance subsequent to acute oxygen desaturation could result in hyperglycemia in rat pups, paralleling symptoms shown in patients with COVID-19 who experienced acute respiratory distress.

The evaluation of serum brain-derived neurotrophic factor and neurofilament light chain levels in patients with obstructive sleep apnea syndrome.

ObjectivesThis study aimed to compare serum levels of brain‐derived neurotrophic factor (BDNF) and neurofilament light (NfL) chain in normal individuals and patients with mild and moderate‐severe obstructive sleep apnea syndrome (OSAS).MethodsWe enrolled 81 subjects referred to Otorhinolaryngology (Ear‐Nose‐Throat), Gazi University Faculty of Medicine, between 2017 and 2019. Based on the severity of OSAS, patients were divided into three groups: group 1 with mild OSAS (apnea‐hypopnea index [AHI] 5‐15; n = 26), group 2 with moderate‐severe OSAS (AHI > 15; n = 32), and group 3 with normal individuals (AHI scores < 5; n = 23).ResultsSerum NfL and BDNF levels were evaluated together with the clinical data for all subjects. Significant differences were seen in the oxygen desaturation index (ODI), apnea index, hypopnea index, sleep efficiency, and NfL levels (P < .05) between the three groups. In the moderate‐severe group, NfL levels showed a significant positive correlation with apnea index (P < .05, r = .389), hypopnea index (P < .05, r = .455), and ODI (P = .04; r = .362).ConclusionsOur findings clarify the pathophysiology of OSAS in cases of repetitive hypoxia and chronic neuronal damage. Based on our results, we recommend that in addition to BDNF, NfL should also be evaluated in different and larger patient cohorts.

Repeated hypoxia exposure induces cognitive dysfunction, brain inflammation, and amyloidβ/p-Tau accumulation through reduced brain O-GlcNAcylation in zebrafish

Repetitive hypoxia (RH) exposure affects the initiation and progression of cognitive dysfunction, but little is known about the mechanisms of hypoxic brain damage. In this study, we show that sublethal RH increased anxiety, impaired learning and memory (L/M), and triggered downregulation of brain levels of glucose and several glucose metabolites in zebrafish, and that supplementation of glucose or glucosamine (GlcN) restored RH-induced L/M impairment. Fear conditioning (FC)-induced brain activation of and PKA/CREB signaling was abrogated by RH, and this effect was reversed by GlcN supplementation. RH was associated with decreased brain O-GlcNAcylation and an increased O-GlcNAcase (OGA) level. RH increased brain inflammation and p-Tau and amyloid β accumulation, and these effects were suppressed by GlcN. Our observations collectively suggest that changes in O-GlcNAc flux during hypoxic exposure could be an important causal factor for neurodegeneration, and that supplementation of the HBP/O-GlcNAc flux may be a potential novel therapeutic or preventive target for addressing hypoxic brain damage.

Obstructive sleep apnoea syndrome (OSAS) as a risk factor for secondary osteoporosis in children

Repetitive hypoxia seen in obstructive sleep apnoea syndrome (OSAS) may affect bone metabolism increasing the risk for secondary osteoporosis. This study investigates the association between OSAS in children and secondary osteoporosis. This cross-sectional study included 150 children aged 10–17 years: 86 with OSAS and 64 with no OSAS. OSAS was confirmed by polysomnography. Quantitative ultrasound (QUS) of calcaneum measuring speed of sound (SoS) and broadband ultrasound attenuation (BUA) were collected. Other parameters collected including bone profile, vitamin D levels, physical activity scoring and dietary calcium intake. Majority were male and Malay ethnicity. OSAS children were mostly obese (84%) and 57% had moderate to severe OSAS. Most had lower physical activities scores. Mean (SD) phosphate and Alkaline phosphatase were lower in OSA children compared to controls: PO4, p = 0.039 and ALP, p < 0.001. Using both single and multivariate analysis, children with OSAS had a lower mean SoS value, p < 0.001 and p = 0.004 respectively after adjusting for age, BMI and bone profile. Children with OSAS had lower SoS suggesting risk for secondary osteoporosis. QUS calcaneus is a non-invasive, feasible tool and can be used to screen risk of osteoporosis in children. Further bone mineral density assessment is needed in these groups of children to confirm diagnosis of osteoporosis.

Narrative review of sleep and pulmonary hypertension.

Pulmonary hypertension (PH) is a condition of raised pulmonary artery pressure (PAP), which may be secondary to a number of causes, one of which is sleep disordered breathing (SDB). When PH complicates SDB, it carries a significant burden of morbidity and mortality due to the risk of progression to right ventricular failure over time. This narrative review will cover the definition and classification of PH, and explore the epidemiology of PH in SDB. The mechanisms by which the two conditions are linked will be reviewed. Repetitive hypoxia with or without hypercapnia alongside frequent arousals can result in important metabolic and pulmonary vascular consequences for the left and right heart. MEDLINE was used to search for all relevant articles and abstracts published from January 1960 to October 2019 inclusive (in all languages). Current best practice in the investigation and management of PH complicating SDB will be reviewed. Important diagnostic investigations and when to consider and screen further for PH in patients with SDB will be discussed. Optimal disease management must include control of SDB with therapy. Additional treatment options will be reviewed. Areas for further research will be highlighted.

Periodic breathing is associated with blood pressure above the recommended target in patients with type 2 diabetes

BackgroundDue to its prognostic importance for patients with type 2 diabetes (DM2), current guidelines recommend a systolic <130 mm Hg and diastolic <80 mm Hg blood pressure target. Periodic breathing, a form of sleep-disordered breathing, acutely causes repetitive hypoxia, sympathetic nervous system activation as well as oscillations of heart rate and blood pressure. However, limited data on the association of periodic breathing and control of blood pressure (BP) in patients with DM2 are available. Thus, the aim of the present study was to assess whether there is an association between periodic breathing and increased BP above the recommended target in DM2. MethodsCross-sectional data of 679 patients with DM2 from the DIACORE-SDB sub-study were analysed for association of periodic breathing with BP. Sleep-disordered breathing was assessed with a 2-channel ambulatory monitoring device including validated automatic pattern recognition for periodic breathing. BP values were determined in a standardized manner with three repeated measurements at rest. ResultsOf the 679 analysed individuals (61% male, age 66 ± 9 years, Body Mass Index [BMI] 31.0 ± 5.4 kg/m2), 11% had periodic breathing. Patients with periodic breathing had significantly higher systolic BP values (144 ± 19 mm Hg vs. 137 ± 18 mm Hg, p = 0.003). Multivariable regression analysis revealed that periodic breathing was associated with higher systolic BP (B [95% confidence interval, CI] = 4.4 [0.1; 8.7], p = 0.043) and not meeting the recommended BP target for patients with diabetes (<130/80 mmHg) (odds ratio, OR [95%CI] = 2.1 [1.1; 4.0], p = 0.026) independent of sex, age, high density lipoproteins, renal function, coronary heart disease and antihypertensive treatment. ConclusionPeriodic breathing is associated with higher systolic BP in patients with DM2.

Long-term facilitation of catecholamine secretion from adrenal chromaffin cells of neonatal rats by chronic intermittent hypoxia.

In neonates, catecholamine (CA) secretion from adrenal medullary chromaffin cells (AMC) is an important mechanism for maintaining homeostasis during hypoxia. Nearly 90% of premature infants experience chronic intermittent hypoxia (IH) because of high incidence of apnea of prematurity, which is characterized by periodic stoppage of breathing. The present study examined the effects of repetitive hypoxia, designed to mimic apnea of prematurity, on CA release from AMC of neonatal rats. Neonatal rats were exposed to either control conditions or chronic intermittent hypoxia (IH) from ages postnatal days 0-5 (P0-P5), and CA release from adrenal medullary slices was measured after challenge with repetitive hypoxia (5 episodes of 30-s hypoxia, Po2 ~35 mmHg). In response to repetitive hypoxia, chronic IH-treated AMC exhibited sustained CA release, and this phenotype was not seen in control AMC. The sustained CA release was associated with long-lasting elevation of intracellular Ca2+ concentration ([Ca2+]i), which was due to store-operated Ca2+ entry (SOCE). 2-Aminoethoxydiphenyl borate, an inhibitor of SOCE, prevented the long-lasting [Ca2+]i elevation and CA release. Repetitive hypoxia increased H2O2 abundance, and polyethylene glycol (PEG)-catalase, a scavenger of H2O2 blocked this effect. PEG-catalase also prevented repetitive hypoxia-induced SOCE activation, sustained [Ca2+]i elevation, and CA release. These results demonstrate that repetitive hypoxia induces long-term facilitation of CA release in chronic IH-treated neonatal rat AMC through sustained Ca2+ influx mediated by SOCE.NEW & NOTEWORTHY Apnea of prematurity and the resulting chronic intermittent hypoxia are major clinical problems in neonates born preterm. Catecholamine release from adrenal medullary chromaffin cells maintains homeostasis during hypoxia in neonates. Our results demonstrate that chronic intermittent hypoxia induces a hitherto uncharacterized long-term facilitation of catecholamine secretion from neonatal rat chromaffin cells in response to repetitive hypoxia, simulating hypoxic episodes encountered during apnea of prematurity. The sustained catecholamine secretion might contribute to cardiovascular morbidities in infants with apnea of prematurity.

PACAP-PAC1 Receptor Activation Is Necessary for the Sympathetic Response to Acute Intermittent Hypoxia.

Repetitive hypoxia is a key feature of obstructive sleep apnoea (OSA), a condition characterized by intermittent airways obstruction. Patients with OSA present with persistent increases in sympathetic activity and commonly develop hypertension. The objectives of this study were to determine if the persistent increases in sympathetic nerve activity, known to be induced by acute intermittent hypoxia (AIH), are mediated through activation of the pituitary adenylate cyclase activating polypeptide (PACAP) signaling system. Here, we show that the excitatory neuropeptide PACAP, acting in the spinal cord, is important for generating the sympathetic response seen following AIH. Using PACAP receptor knockout mice, and pharmacological agents in Sprague Dawley rats, we measured blood pressure, heart rate, pH, PaCO2, and splanchnic sympathetic nerve activity, under anaesthesia, to demonstrate that the sympathetic response to AIH is mediated via the PAC1 receptor, in a cAMP-dependent manner. We also report that both intermittent microinjection of glutamate into the rostroventrolateral medulla (RVLM) and intermittent infusion of a sub-threshold dose of PACAP into the subarachnoid space can mimic the sympathetic response to AIH. All the sympathetic responses are independent of blood pressure, pH or PaCO2 changes. Our results show that in AIH, PACAP signaling in the spinal cord helps drive persistent increases in sympathetic nerve activity. This mechanism may be a precursor to the development of hypertension in conditions of chronic intermittent hypoxia, such as OSA.

Age and autonomic control, but not cerebral oxygenation, are significant determinants of EEG spectral power in children.

Sleep disordered breathing (SDB) in children has significant effects on daytime functioning and cardiovascular control; attributed to sleep fragmentation and repetitive hypoxia. Associations between electroencephalograph (EEG) spectral power, autonomic cardiovascular control and cerebral oxygenation have been identified in adults with SDB. To date, there have been no studies in children. We aimed to assess associations between EEG spectral power and heart rate variability as a measure of autonomic control, with cerebral oxygenation in children with SDB. One hundred sixteen children (3-12 years) with SDB and 42 controls underwent overnight polysomnography including measurement of cerebral oxygenation. Power spectral analysis of the EEG derived from C4-M1 and F4-M1, quantified delta, theta, alpha, and beta waveforms during sleep. Multiple regression tested whether age, SDB severity, heart rate (HR), HR variability (HRV), and cerebral oxygenation were determinants of EEG spectral power. There were no differences in EEG spectral power derived from either central or frontal regions for any frequency between children with different severities of SDB so these were combined. Age, HR, and HRV low frequency power were significant determinants of EEG spectral power depending on brain region and sleep stage. The significant findings of this study were that age and autonomic control, rather than cerebral oxygenation and SDB severity, were predictive of EEG spectral power in children. Further research is needed to elucidate how the physiology that underlies the relationship between autonomic control and EEG impacts on the cardiovascular sequelae in children with SDB.

The impact of central and obstructive respiratory events on cerebral oxygenation in children with sleep disordered breathing.

Both central and obstructive respiratory events are features of sleep disordered breathing. The repetitive hypoxia associated with obstructive events is believed to underpin the adverse neurocognitive and cardiovascular sequelae of this disorder, however whether central events contribute to this has not been investigated. To compare changes in cerebral and peripheral oxygenation, blood pressure and heart rate, associated with central and obstructive events in children aged 3-6 and 7-12 years. Sixty children referred for suspected sleep disordered breathing underwent overnight polysomnography. Beat-by-beat analysis determined changes from baseline in cerebral oxygenation, peripheral oxygen saturation, fractional tissue oxygen extraction, pulse transit time (a surrogate measure of blood pressure change), and heart rate, associated with central and obstructive respiratory events, during NREM and REM sleep. Eight hundred ninty-two events were analyzed: 493 central and 399 obstructive. Central events had a greater % change from baseline in cerebral oxygenation and heart rate nadir compared with obstructive events and these were greater in NREM compared with REM sleep. The 3- to 6-year-old children experienced a greater % change in TOI compared with the 7-12 year olds, while % change in heart rate was greater in 7-12 year olds. Central respiratory events had similar falls in cerebral oxygenation and heart rate to obstructive events and should be considered when examining the sequelae of sleep disordered breathing, particularly as central events are common in children with sleep disordered breathing.

UHPLC-QTOFMS-Based Metabolomic Analysis of the Hippocampus in Hypoxia Preconditioned Mouse

Background: Hypoxia appears in a number of extreme environments, including high altitudes, the deep sea, and during aviation, and occurs in cancer, cardiovascular disease, respiratory failures and neurological disorders. Though it is well recognized that hypoxic preconditioning (HPC) exerts endogenous neuroprotective effect against severe hypoxia, the mediators and underlying molecular mechanism for the protective effect are still not fully understood. This study established a hippocampus metabolomics approach to explore the alterations associated with HPC.Methods: In this study, an animal model of HPC was established by exposing the adult BALB/c mice to acute repetitive hypoxia four times. Ultra-high liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) in combination with univariate and multivariate statistical analyses was employed to deciphering metabolic changes associated with HPC in hippocampus tissue. MetaboAnalyst 3.0 was used to construct HPC related metabolic pathways.Results: The significant metabolic differences in hippocampus between the HPC groups and control were observed, indicating that HPC mouse model was successfully established and HPC could caused significant metabolic changes. Several key metabolic pathways were found to be acutely perturbed, including phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, phenylalanine metabolism, glutathione metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, citrate cycle, and glycerophospholipid metabolism.Conclusion: The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the neuroprotective mechanism of HPC.