Hypercapnic Hypoxia Research Articles

Are parenteral steroids for epileptic encephalopathy with electrical status epilepticus during sleep effective for associated autistic disorder?

Chronic exposure to intermittent hyperoxia causes abnormal carotid body development and attenuates the hypoxic ventilatory response (HVR) in neonatal rats. We hypothesized that concurrent exposure to intermittent hypercapnic hypoxia would influence this plasticity. Newborn rats were exposed to alternating bouts of hypercapnic hypoxia (10% O2/6% CO2) and hyperoxia (30–40% O2) (5 cycles h−1, 24 h d−1) through 13–14 days of age; the experiment was run twice, once in a background of 21% O2 and once in a background of 30% O2 (i.e., “relative hyperoxia”). Hyperoxia had only small effects on carotid body development when combined with intermittent hypercapnic hypoxia: the carotid chemoafferent response to hypoxia was reduced, but this did not affect the HVR. In contrast, sustained exposure to 30% O2 reduced carotid chemoafferent activity and carotid body size which resulted in a blunted HVR. When given alone, chronic intermittent hypercapnic hypoxia increased carotid body size and reduced the hypercapnic ventilatory response but did not affect the HVR. Overall, it appears that intermittent hypercapnic hypoxia counteracted the effects of hyperoxia on the carotid body and prevented developmental plasticity of the HVR.

Reaction of hemostasis system in hypercapnic hypoxia after the course of mexidol assessed by the method of thromboelastography

Aim. To study the reaction of hemostasis system to a single effect of hypercapnic hypoxia of maximum intensity in rats and possibility of correcting hemostasis disorders by means of a preliminary course of an antihypoxant - mexidol. Methods. The study involved sexually mature male rats (48 specimens) of the Wistar line with an average mass of 274.0 ± 32.0 g. The rats were kept on a standard diet, food and water were fed once a day between 10 and 11 hours. In the evening, animals underwent a single hypercapnic hypoxia in a special flow chamber. The state of hypercapnic hypoxia of maximum intensity was modeled at O2 content of 5.0 %, CO2 - 5.0 % during a single 20-minute exposure. As a training regimen, a 30-fold course of mexidol was used, the drug was administered intraperitoneally to rats at a dose of 50 mg/kg for 1.5 hours prior to exposure to hypercapnic hypoxia. Results. After a single exposure to hypercapnic hypoxia of maximum intensity, shortening of the onset of clot formation, an increase of alpha angle, and maximum clot density were recorded. Also, the clot formation time shortened and the maximum clot lysis index increased. With a single exposure to hypercapnic hypoxia of maximum intensity after the course of mexidol, a decrease in the maximum clot density was recorded. Conclusion. A single exposure to hypercapnic hypoxia of maximum intensity was characterized by a shift of hemostatic potential toward hypercoagulability along with fibrinolytic system activation. The course use of antihypoxant mexidol, preceding hypercapnic hypoxia of maximum intensity, significantly reduces the risk of clot formation.

Combined effects of intermittent hyperoxia and intermittent hypercapnic hypoxia on respiratory control in neonatal rats

Chronic exposure to intermittent hyperoxia causes abnormal carotid body development and attenuates the hypoxic ventilatory response (HVR) in neonatal rats. We hypothesized that concurrent exposure to intermittent hypercapnic hypoxia would influence this plasticity. Newborn rats were exposed to alternating bouts of hypercapnic hypoxia (10% O2/6% CO2) and hyperoxia (30–40% O2) (5 cycles h−1, 24 h d−1) through 13–14 days of age; the experiment was run twice, once in a background of 21% O2 and once in a background of 30% O2 (i.e., “relative hyperoxia”). Hyperoxia had only small effects on carotid body development when combined with intermittent hypercapnic hypoxia: the carotid chemoafferent response to hypoxia was reduced, but this did not affect the HVR. In contrast, sustained exposure to 30% O2 reduced carotid chemoafferent activity and carotid body size which resulted in a blunted HVR. When given alone, chronic intermittent hypercapnic hypoxia increased carotid body size and reduced the hypercapnic ventilatory response but did not affect the HVR. Overall, it appears that intermittent hypercapnic hypoxia counteracted the effects of hyperoxia on the carotid body and prevented developmental plasticity of the HVR.

The role of endoplasmic reticulum stress in pulmonary hypertension in rat induced by chronic hypoxia and hypercapnia

To observe the pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia, and to explore the role of endoplasmic reticulum stress in pulmonary hypertension. Forty SD rats were random-ly divided into four groups:normoxic control group (N), hypoxia hypercapnia group (HH), ERS inhibitor 4-phenylbutyric acid group (4-PBA), endoplasmic reticulum stress (ERS) pathway agonist tunicamycin group (TM), ten rats in each group.The mean pulmona-ry artery pressure (mPAP), mean carotid artery pressure (mCAP) and right ventricular hypertrophy index of rats in each group were measured.Pulmonary artery smooth muscle cells were identified by immunofluorescence α-smooth muscle actin (α-SMA).Morphologi-cal changes of lung tissue and pulmonary artery were observed by electron microscope.The apoptotic index of pulmonary artery smooth muscle cells in each group was detected by TUNEL.Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), c-Jun N-terminal kinase (JNK) and cysteinyl aspartate specific proteinase-12 (caspase-12) mRNA and protein in each group. ①Compared with the N group, the mPAP, the ratio of right ventricle weight to left ventricle plus ventricular septum weight[RV/(LV+S)]and the ratio of pulmonary artery wall area to total tube area (WA/TA) were increased (P<0.01), and the ratio of pulmonary artery luminal area to total tube area (LA/TA) were decreased (P<0.01), pulmonary artery smooth muscle cell apoptosis index were decreased (P<0.05 or P<0.01) in HH group, 4-PBA group and TM group.ERS related protein and mRNA expressions were increased, the differences were statistically significant.②Compared with the HH group, the mPAP, [RV/(LV+S)]and WA/TA of 4-PBA group were decreased (P <0.01), LA/TA and pulmonary artery smooth muscle cell apoptosis index were increased (P<0.01, P<0.05).The expressions of ERS related protein and mRNA were all decreased (P<0.05 or P<0.01).③Compared with the HH group, the mPAP, [RV/(LV+S)]and WA/TA of TM group were increased (P<0.05 or P<0.01), pulmonary artery middle layer thickened, LA/TA and pulmonary artery smooth muscle cell apoptotic index were decreased (P<0.01).ERS related protein and mRNA expressions were increased with statistical significance except GRP78 protein. Pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia may be related to the excessive proliferation of pulmonary artery smooth muscle cells and too little apopto-sis;ERS related factors (JNK, caspase-12 and CHOP) are involved in the regulation of pulmonary hypertension induced by hypoxia hypercapnia.

The Pattern of Breathing in Young Wild Type and Ts65Dn Mice During the Dark and Light Cycle

Down syndrome (Ds) results from trisomy 21 and is the most common cause of mental retardation in the US. People with Ds display muscle weakness and cardiorespiratory complications that may contribute to their altered breathing. Ts65Dn mice, a model of Ds, have been shown to exhibit altered breathing at 12 months of age. It is unknown when breathing changes occur in these mice but it is hypothesized to be later in development based on muscle alterations reported in the literature. An additional study found hypoxemia to be more common in the dark vs. light cycle in Ts65Dn mice. We tested the hypothesis that 3‐month Ts65Dn mice would display an altered pattern of breathing compared to wild‐type (WT) mice, and that responses would differ between dark and light cycles. In order to test these hypotheses, unrestrained barometric plethysmography was used to quantify breathing frequency (breaths/min; BPM), tidal volume (TV; mL/breath) and minute ventilation (MV; mL/min) in 3‐month old Ts65Dn (n=3) and WT (n=4) mice. Mice were tested between hours 8–10 of the dark cycle and between hours 7–9 of the light cycle. Implantable LifeChips (Destron Fearing, Airport, TX) were used to monitor body temperature; changes of more than 1 degree were accounted for in the analyses. Ponemah software (Data Sciences International, St. Paul, MN) was used to analyze flow tracings during exposure to air (20.93% O2, balanced N2), hypoxia (10% O2, balanced N2), hypercapnia (5% CO2, balanced air) and hypoxic hypercapnia (10% O2, 5% CO2, balanced N2). Data are expressed as MEAN±SD; p&lt;0.05; WT vs. Ts65Dn. Body weight was not different between WT and Ts65Dn mice (37.5±4.2 vs. 37.7±5.8g). The delta for dark minus light cycle were analyzed with repeated measures two‐way ANOVA, with strain and gas exposure as factors. An interaction between strain and gas exposures was found for MV and breathing frequency. No interaction was detected for TV. The delta for frequency are described for quiet breathing (12±7 vs. −3±36 BPM), hypoxia (6±31 vs. 8±15 BPM), hypercapnia (61±32 vs. 48±25 BPM), hypoxic hypercapnia (48±37 vs. 35±38 BPM) and recovery (−14±64 vs. 156±49 BPM). MV deltas are listed for quiet breathing (−0.9±21.9 vs. 20.8±33.8 mL/min), hypoxia (−0.9±38.8 vs. 24.9±21.9 mL/min), hypercapnia (32.5±72.3 vs. 71.1±68.1 mL/min), hypoxic hypercapnia (25.8±78.2 vs. 66.9±81.8 mL/min) and recovery (10.8±46.5 vs. 146.7±107.1 mL/min). Once more data are collected, the repeated measures two‐way ANOVA will be re‐run, and post‐hoc analysis will be performed for each gas exposure. Apnea count (no flow ≥0.5 sec) showed cycle (light/dark) and strain differences, along with a cycle by strain interaction. Light cycle apneas were more common (16±17/hr vs. 81±40/hr; WT vs. Ts65Dn) compared to the dark cycle (7±12/hr vs. 51±35/hr; WT vs. Ts65Dn); apneas were more prevalent in Ts65Dn mice overall. This preliminary study indicates the Ts65Dn mouse model may have a greater delta magnitude (dark minus light) when comparing the pattern of breathing to WT mice in dark and light cycles. The apnea count in Ts65Dn is suggestive of a lower neural drive to breath in these mice vs. WT. Additional data will be collected to identify if these initial findings continue in Ts65Dn and WT mice.Support or Funding InformationFunded by 1 R15 HD076379‐01A1, CNR supported by 1 R15 HD076379‐01A1S1.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Respiratory EMG responsiveness to hypercapnic hypoxia in mdx mice

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease characterised by the absence of the structural protein dystrophin. Respiratory failure is the leading cause of premature death in DMD. Although respiratory insufficiency is recognized as a hallmark of DMD, respiratory control is relatively understudied. We hypothesized that enhanced drive in accessory respiratory motor pathways preserves ventilatory capacity compensating for severe respiratory muscle weakness.We utilised the C57BL/10ScSn‐Dmdmdx/J (mdx) mouse model. Respiratory flow recordings were performed in freely‐behaving wild‐type (WT, n=9) and mdx (n=7) mice at ~8 weeks of age using whole‐body plethysmography to determine ventilation (VE), oxygen consumption (VO2) and carbon dioxide production (VCO2). Baseline recordings were performed in normoxia, followed by chemostimulation using hypercapnic hypoxic gas challenge (FiO2=0.10; FiCO2=6; balance N2). In urethane (1.6 g/kg) anaesthetised WT (n=13) and mdx (n=14) mice, diaphragm, intercostal and genioglossus EMG and motor unit recordings were performed during baseline conditions and in response to chemostimulation.Plethysmographic recordings revealed that during chemostimulation, minute ventilation (VE) is equivalent in WT and mdx mice, highlighting a considerable ventilatory reserve in young mdx despite substantial diaphragm muscle weakness. Moreover, diaphragm, intercostal and genioglossus EMG responsiveness to hypercapnic hypoxia was equivalent in WT and mdx mice.Despite substantial diaphragm weakness and evidential muscle fibre damage and remodelling, freely behaving mdx mice can achieve enhanced ventilation during chemostimulation to levels equivalent to that of WT animals. We found no evidence of enhanced activity in respiratory muscle EMGs. Assessment of the motor unit population will allow for the comparison of the phenomena of rate coding and recruitment during increased respiratory muscle activation. Our study suggests that respiratory muscle weakness in young mdx does not compromise ventilator behaviour but is likely to have considerable impact on airway protective behaviours.Support or Funding InformationDepartment of Physiology, University College Cork, Cork, IrelandThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans.

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po2 and Pco2 or if coronary vascular responses are the result of concomitant increases in myocardial O2 consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po2 and Pco2 would be attenuated in healthy men when [Formula: see text] was attenuated with β1-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β1-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and after 5 min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LADV; Doppler echocardiography), heart rate, and arterial blood pressure. LADV values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (MELV) were calculated as indexes of [Formula: see text]. All gas manipulations augmented RPP, MELV, and LADV, but only RPP and MELV were attenuated (4-18%) after β1-adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and MELV responses, β1-adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 ± 2.2 vs. 27.3 ± 1.6 cm/s) and isocapnic hypoxia (29.5 ± 1.5 vs. 30.3 ± 2.2 cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was blocked by β1-adrenergic receptor blockade. These results indicate a direct influence of arterial Po2 on coronary vascular regulation that is independent of [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β1-Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O2 demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O2 consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β1-adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of Po2 and Pco2 during hypercapnic hypoxia.

СОЧЕТАНИЕ ГИПЕРКАПНИИ И ГИПОКСИИ ПРИВОДИТ К АЦИДОЗУ И УВЕЛИЧИВАЕТ СОДЕРЖАНИЕ HIF-LA В ГИППОКАМПЕ КРЫС

The gas composition of the arterial blood and the HIF-1a expression in hippocampal neurons of rats were measured after 7-day long daily 30-minute treatment with isolated or combined permissive hypercapnia (PCO2 = 50 mmHg) and moderate hypoxia (PO2 = 90 mmHg). HIF-1a expression was increased in the hippocampus after combined, but not isolated, treatment with moderate hypercapnia and hypoxia. The hypercapnic and/or hypoxic gas composition of the inhaled air defined the corresponding gas composition of the blood. The arterial CO2 was lower in the normobaric hypoxia group compared to control, while remaining in the normocapnic range. The arterial O2 in hypercapnic hypoxia was lowered, but not as low as in isolated hypoxia. Hypercapnia, both isolated and in combination with hypoxia, lowered the blood pH and thus led to the acidosis.

Комплексное лечение больных хроническим абактериальным простатитом с использованием гиперкапнической гипоксии

Комплексное лечение больных хроническим абактериальным простатитом с использованием гиперкапнической гипоксии

P53 gene cloning and response to hypoxia in the plateau zokor, Myospalax baileyi

Abstract The plateau zokor (Myospalax baileyi) is a specialized subterranean rodent that lives on the Qinghai-Tibet Plateau. The species has evolved a series of strategies to adapt to its hypoxic environment and hypercapnia. p53 is a tumour suppressor gene that plays a crucial role in the cellular response to hypoxia by inducing cell cycle arrest, cell apoptosis, DNA damage repair and angiogenesis. To investigate the sequence characteristics of p53 and the response to hypoxia in plateau zokor, we cloned the p53 coding DNA sequence, analysed it, and measured the expression level of p53 at different altitudes in plateau zokor and rats. Our results show that the coding DNA sequence is 1179 bp, consisting of 392 amino acid residues. Compared to human p53, the subterranean rodents have two mutation sites in common with the human hotspots in the DNA-binding domain. Compared to subterranean rodents, plateau zokor have a mutation at residue 309. In addition, subterranean rodents have two convergent sites at residues 78 and 84. The expression levels of p53 in plateau zokor tissues increase significantly from 2260 m to 3300 m, but there was no significant difference in rats at those altitudes. Our results suggest that subterranean rodents have two mutation sites in common with the human hotspots in the DNA-binding domain, the mutation of Gly309Asp is a unique mutation site of plateau zokor p53, and there are two convergent sites enhancing subterranean rodent adaptation to hypoxic conditions. In addition, p53 is sensitive to the oxygen concentration in plateau zokor, and hypoxia upregulates the levels of p53. Generally, plateau zokor use this strategy to adapt to a hypoxic environment.

Effects of Endoplasmic Reticulum Stress on Pulmonary Hypertension in Rat Induced by Chronic Hypoxia and Hypercapnia

Objective: To observe the pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia, and to explore the role of endoplasmic reticulum stress in pulmonary hypertension. Methods: 1) 40 SD rats were randomly divided into four groups: normoxic control group (N), hypoxia hypercapnia group (HH), endoplasmic reticulum stress (ERS) inhibitor 4-phenyl butyric acid group (4-PBA), ERS pathway agonist tunicamycin group (TM). 2) The mean pulmonary arterial pressure (mPAP) and the right ventricular hypertrophy index (RV/(LV + S)) were measured in each group. 3) Identification of pulmonary artery smooth muscle cells (PASMCs) in each group by immunofluorescence α-SMA. 4) Morphological changes of lung tissue and pulmonary artery were observed by electron microscope. 5) The apoptotic index of PASMCs in each group was detected by TUNEL. 6) Reverse transcription polymerase chain reaction (RT-PCR) and Western Blot (WB) were used to detect the expression of ERS related protein and mRNA (GRP78, CHOP, JNK, Caspase-12) in each group. Results: 1) Compared with the N group, the mPAP, RV/(LV + S) and vascular wall area (WA)/total area (TA) value of HH group, 4-PBA group and TM group were increased (P P P P P P P P P P Conclusion: Hypoxia and hypercapnia induced pulmonary vascular remodeling may be related to the proliferation of PASMCs, and ERS related factors (JNK, Caspase12 and CHOP) are involved in the regulation of hypoxic hypercapnia.

The relationship between acidosis and hypercapnia with Cor pulmonale in patients with chronic obstructive pulmonary disease

Introduction: Cor pulmonale or right ventricular (RV) enlargement is cardiovascular complication of the chronic obstructive pulmonary disease (COPD). Hypoxic pulmonary vasoconstriction, hypercapnia, acidosis and pulmonary vascular remodeling are suggested as possible mechanisms of cor pulmonale. In this study, we aimed to evaluate the correlation between acidosis and hypercapnia with corpulmonale in patients with COPD. Methods: In this cross-sectional analytical study, 100 patients (56 men and 44 women with mean age of 66.53 ± 10.63 years) with moderate to severe COPD exacerbation were included. Complete history taking and physical examination as well as atrial blood gas, pulmonary function test (PFT) and echocardiography were performed. Disease severity was defined according to global initiative for obstructive lung disease (GOLD), Modified Medical Research Council (mMRC) and COPD Assessment Test (CAT) criteria. Patients with cor pulmonale were defined and findings were compared between patients with and without cor pulmonale. Results: Forty-two patients had cor pulmonale. There was no significant difference in hypercapnia between groups. Cor pulmonale patients, compared to non-cor pulmonale, had significantly lower forced expiratory volume in the first second (FEV1) (P = 0.020), higher tricuspid regurgitation (TR) (P = 0.001) and pulmonary hypertension (P = 0.020). There was significantly negative correlation between RV thickness with FEV1/forced vital capacity (FCV) (r = -0.239, P = 0.010) and RV size with FEV1/FVC (r = -0.312, P = 0.002) and positive correlation with partial pressure of carbon dioxide (PaCO2) (r = 0.312, P = 0.002) and bicarbonate (HCO3) (r = 0.258, P = 0.009). Conclusion: Cor pulmonale in the course of COPD accompanies with adverse outcome. These patients have worse spirometry and left ventricle echocardiographic findings, but have no difference in arterial blood gas (ABG) findings.

A non-invasive magnetic resonance imaging approach for assessment of real-time microcirculation dynamics

We present a novel, non-invasive magnetic resonance imaging (MRI) technique to assess real-time dynamic vasomodulation of the microvascular bed. Unlike existing perfusion imaging techniques, our method is sensitive only to blood volume and not flow velocity. Using graded gas challenges and a long-life, blood-pool T1-reducing agent gadofosveset, we can sensitively assess microvascular volume response in the liver, kidney cortex, and paraspinal muscle to vasoactive stimuli (i.e. hypercapnia, hypoxia, and hypercapnic hypoxia). Healthy adult rats were imaged on a 3 Tesla scanner and cycled through 10-minute gas intervals to elicit vasoconstriction followed by vasodilatation. Quantitative T1 relaxation time mapping was performed dynamically; heart rate and blood oxygen saturation were continuously monitored. Laser Doppler perfusion measurements confirmed MRI findings: dynamic changes in T1 corresponded with perfusion changes to graded gas challenges. Our new technique uncovered differential microvascular response to gas stimuli in different organs: for example, mild hypercapnia vasodilates the kidney cortex but constricts muscle vasculature. Finally, we present a gas challenge protocol that produces a consistent vasoactive response and can be used to assess vasomodulatory capacity. Our imaging approach to monitor real-time vasomodulation may be extended to other imaging modalities and is valuable for investigating diseases where microvascular health is compromised.

Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males.

Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO2 levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO2 and 3.0 ± 0.2% O2) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO2, O2 saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea.NEW & NOTEWORTHY Both arousal state and concomitant CO2 levels are known modulators of the effects of intermittent hypoxia on ventilatory neuroplasticity. This is the first study to investigate the effects of combined intermittent hypercapnic hypoxia during sleep in humans. The lack of neuroplastic effects suggests a need for further studies more closely replicating obstructive sleep apnea to determine the pathophysiological relevance of intermittent hypoxia-induced ventilatory neuroplasticity.

Hypoxia and nicotine effects on Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor 1 (PAC1) in the developing piglet brainstem

Pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate receptor 1 (PAC1), have been implicated in the pathophysiology of the Sudden Infant Death Syndrome (SIDS). Two main risk factors for SIDS are prone sleeping and cigarette smoke exposure. Using piglet models of these risk factors, intermittent hypercapnic hypoxia (IHH-mimicking rebreathing in prone position) and nicotine (main reinforcing element of cigarettes), this study aimed to determine their effects on PACAP and PAC1 protein expression in the medulla. IHH was delivered for 1 (n=7), 2 (n=6), 3 (n=6) and 4 (n=7) days prior to euthanasia at 13–14days of age, while nicotine (n=7) was continuous for the first 14days of life. An additional group of combined nicotine and 1day IHH (1DIHH) was studied to determine the combined effects of the risk factors. Changes in expression were seen after the acute 1DIHH exposure (none after repeated daily exposures) and included a decrease in PACAP in the dorsal motor nucleus of vagus (DMNV; p=0.024), nucleus of the solitary tract (NTS; p=0.024) and the gracile nucleus (GRAC; p=0.001), and a decrease in PAC1 in the NTS (p=0.01). No PACAP change was noted in the nicotine-exposed piglets, however, a decrease in PAC1 was found in the DMNV (p=0.02). IHH exposure in piglets with pre-exposure to nicotine led to a significant decrease in PACAP in the Grac (p=0.04) but had no effect on PAC1. These findings show for the first time, the vulnerability of PACAP in the brainstem during early development to an acute hypercapnic hypoxic exposure and that those effects are greater than from nicotine exposure.

Does reduced carotid body BDNF contribute to developmental hyperoxia‐induced respiratory plasticity?

Chronic exposure to moderate hyperoxia (60% O2) reduces carotid body expression of brain‐derived neurotrophic factor (BDNF) in neonatal rats. Reduced BDNF expression correlates with abnormal carotid body development and blunted hypoxic ventilatory responses, but a causal relationship has not been established. First, we used ELISA to confirm that both sustained and intermittent exposures to 60% O2 reduced carotid body BDNF levels; intermittent hypercapnic hypoxia had the opposite effect. Next, we attempted to block the effects of developmental hyperoxia by administering LM22A4 (50 mg kg−1, i.p., daily), an agonist for BDNF's TrkB receptor. After 7 days of treatment with 60% O2, carotid body volume and the hypoxic ventilatory response were significantly reduced in P7 rats that received either LM22A4 or vehicle (saline) from birth; the drug treatment did not attenuate this effect. Similar results were obtained using an alternate TrkB agonist, 7,8‐dihydroxyflavone (5 mg kg−1, i.p., daily). Although carotid body BDNF expression appears to be regulated by environmental O2, our data do not support the hypothesis that reduced BDNF is directly responsible for hyperoxia‐induced developmental plasticity in respiratory control.Support or Funding InformationSupported by NIH grant R15 HL‐114001.

The Organization and Content of Music Therapy Classes for the Prevention and Treatmentof Psychosomatic Diseases in Children from Six to Ten Yearsof Age

In preparing of professional field hockey players we should use the additional tools that would help to improve the abdominal type of breathing. This fact would have the positive impact to the improving of their special physicalpreparedness. The goal of the research is to identify the influence of learning and training classes with the use of the method of creating the state of hypercapnic hypoxia on specialized physical preparedness of field hockey players on the stage of the highest possible realization of individual abilities. Results of the study. 29 field hockey players aged 19–21 took part in the study. The study was conducted for 24 weeks of the first preparatory and competitive periods of yearly macro cycle. During the shaping experiment, the athletes' starting speed increased by 10 and 30 meters in 4,37 and 1,89 %, respectively, and the result of the «shuttle run 180 m» test (in 0,73 %) also improved. In hockey players on the grass of the control group, only the running time by 10 m decreased (in 3,21 %). Conclusions. It has been established that studies using the «endogenous-hypoxic breathing» technique contribute to a significant increase in the starting speed and special endurance in conditions of providing muscular work at the expense of lactate energy supply processes.

Neuromuscular electrical stimulation relieves pulmonary artery hypertension associated with chronic hypoxic hypercapnia

Objective To investigate effects of neuromuscular electrical stimulation (NMES) on pulmonary arterial hypertension induced by chronic hypoxic hypercapnia in rats. Methods Eighteen male Sprague-Dawley rats were randomly divided into a normal control group (the control group), a hypoxic hypercapnia group (the model group), and a hypoxic hypercapnia + NMES group (the NMES group), each of 6. The rats in both the model and NMES groups were placed in an isobaric cabin with an O2 concentration of 9% to 11% and a CO2 concentration of 5% to 6% for 8 hours a day for 4 weeks. After leaving the cabin, NMES was performed on the NMES group′s bilateral calf muscles for 30 minutes every day. The heart was removed, and the right ventricle (RV) and the left ventricle plus the septum (LV+ S) were dissected. An index of right ventricular hypertrophy was calculated as RVHI=RV/(LV+ S). Any changes in the pulmonary vasculature were observed using an optical microscope. WT% and WA% were calculated. The expression of hypoxia-inducible factor-1α (HIF-1α), PDH-E1α and PDK1 in the lung tissue were determined using western blotting. The LDH activity and the concentration of PDH in the lung tissue homogenate were measured was measured by spectrophotometric method using the LDH assay kit and ELISA , respectively. Results Compared with the control group, the average RVHI, WT% and WA%, the protein expression of HIF-1α and PDK1, and LDH activity had all increased significantly in the NMES group, while the average expression of PDH-1Eα had decreased significantly. Compared with the model group, significant decrease was observed in the average RVHI, WT%, WA%, protein expression of HIF-1α and PDK1, and LDH activity in the NMES group, but the average expression of PDH-1Eα increased significantly. No significant differences in PDH concentration were detected among the 3 groups. Conclusions NMES may alleviate pulmonary artery hypertension induced by chronic hypoxic hypercapnia, at least in rats. The mechanism may be attributed to inhibiting the expression of HIF-1α protein, which may inhibit the activity of PDH-E1α and LDH, then the aerobic metabolism into glycolysis, finally improving the remodeling of the pulmonary vascular structure. Key words: Hypoxic hypercapnia; Pulmonary arterial hypertension; Neuromuscular electrical stimulation; Hypoxia-inducible factor-1α

Intermittent hypercapnic hypoxia effects on the nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem

This study investigated the effects of acute (1 day) vs repeated (4 days) exposure to intermittent hypercapnic hypoxia (IHH) on the immunohistochemical expression of α2, α3, α5, α7, α9 and β2 nicotinic acetylcholine receptor (nAChR) subunits in the developing piglet hippocampus and brainstem medulla, and how prior nicotine exposure alters the response to acute IHH. Five piglet groups included: 1day IHH (1D IHH, n=9), 4days IHH (4D IHH, n=8), controls exposed only to air cycles for 1day (1D Air, n=6) or 4days (4D Air, n=5), and pre-exposed to nicotine for 13days prior to 1day IHH (Nic+1D IHH, n=7). The exposure period alternated 6min of HH (8%O2, 7%CO2, balance N2) and 6min of air over 48min, while controls were switched from air-to-air. Results showed that: 1. repeated IHH induces more changes in nAChR subunit expression than acute IHH in both the hippocampus and brainstem medulla, 2. In the hippocampus, α2 and β2 changed the most (increased) following IHH and the CA3, CA2 and DG were mostly affected. In the brainstem medulla, α2, α5, α9 and β2 were changed (decreased) in most nuclei with the hypoglossal and nucleus of the solitary tract being mostly affected. 3. Pre-exposure to nicotine enhanced the changes in the hippocampus but dampened those in the brainstem medulla. These findings indicate that the nAChRs (predominantly with the α2/β2 complex) are affected by IHH in critical hippocampal and brainstem nuclei during early brain development, and that pre-exposure to nicotine alters the pattern of susceptibility to IHH.

Notoginsenoside R&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; Attenuates Hypoxia and Hypercapnia-Induced Vasoconstriction &amp;lt;i&amp;gt;In Vitro&amp;lt;/i&amp;gt; by Reducing the Expression of p38

Notoginsenoside R1, the main active ingredient of Panax notoginseng saponins (PNS), has been proposed to play fatal roles in the development of hypoxic hypercapnia-induced pulmonary vasoconstriction (HHPV). Subsequently, pulmonary arterial smooth muscle cells (PASMCs) lead to pulmonary vascular system remodeling and chronic pulmonary disease in the development of HHPV. Despite considerable studies have contributed to pulmonary disease, the mechanism of how Notoginsenoside R1 affects HHPV remains unclear. In this view, we will discuss the effect of notoginsenoside R1 by investigating the expression of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in PASMCs under hypoxia and hypercapnia condition. The third order PASMCs of Sprague Dawley (SD) rats were cultured with various concentrations (8, 40, 100 mg/L, respectively) of Notoginsenoside R1. Our data showed that the protein and mRNA expression levels of p-38 MAPK were higher in hypoxic hypercapnia group compared with hypoxic DMSO and normoxia control groups (p 1 treatment groups, the level of p-p38 MAPK protein and p38 MAPK mRNA were significantly decreased with different degrees (p 1 treatment may contribute to attenuate HHPV via decreasing the protein and mRNA expression levels of p-38 MAPK.