Intermittent Breathing Research Articles

Apneustic anesthesia ventilation improves pulmonary function in anesthetized bottlenose dolphins (Tursiops truncatus).

Use of mechanical ventilation during general anesthesia is a necessary practice in the anesthetization of small cetaceans as spontaneous ventilation fails to provide adequate gas exchange. Currently available methods of ventilation do not account for the intermittent breathing strategy of representative species within this infraorder of fully aquatic mammals and may have a significant effect on cardiac and respiratory physiology. To understand the impact of mechanical ventilation on cardiopulmonary function in one small species of cetacean, the bottlenose dolphin (Tursiops truncatus), we compared controlled mechanical ventilation (CMV) to a novel ventilation method known as apneustic anesthesia ventilation (AAV). AAV simulates the normal inspiratory breath-hold pattern of dolphins. Ten anesthetic procedures (dental procedure, n = 9; bronchoscopy, n = 2) were performed on nine dolphins (age range: 10-42 years; mean = 32 years; median = 37 years; female = 3, 40%; male = 6, 60%). In a cross-over study design, dolphins were instrumented and randomly assigned to AAV or CMV as the initial mode of ventilation, then switched to the alternate mode. Baseline cardiopulmonary data were collected and again after 30 min on each mode of ventilation. Cardiac index, stroke volume index, systemic vascular resistance, alveolar dead space, alveolar-arterial oxygen tension gradient, arterial oxygen content, oxygen delivery index, and dynamic respiratory system compliance index were calculated at each of the four time points. During AAV, dolphins had higher arterial oxygen tension, higher mean airway pressure, reduced alveolar dead space ventilation and lower alveolar-arterial oxygen difference. Cardiovascular performance was not statistically different between the two modes. Our study suggests AAV, which more closely resembles the conscious intermittent respiratory pattern phenotype of dolphins, improves ventilation and pulmonary function in the anesthetized dolphin. Future studies should evaluate the cardiopulmonary effects of neutral buoyancy and cardiopulmonary sparing drug protocols to reduce the need for hemodynamic support of current protocols.

Breathing patterns and associated cardiovascular changes in intermittently breathing animals: (Partially) correcting a semantic quagmire.

Many animal species do not breathe in a continuous, rhythmic fashion, but rather display a variety of breathing patterns characterized by prolonged periods between breaths (inter-breath intervals), during which the heart continues to beat. Examples of intermittent breathing abound across the animal kingdom, from crustaceans to cetaceans. With respect to human physiology, intermittent breathing-also termed 'periodic' or 'episodic' breathing-is associated with a variety of pathologies. Cardiovascular phenomena associated with intermittent breathing in diving species have been termed 'diving bradycardia', 'submersion bradycardia', 'immersion bradycardia', 'ventilation tachycardia', 'respiratory sinus arrhythmia' and so forth. An examination across the literature of terminology applied to these physiological phenomena indicates, unfortunately, no attempt at standardization. This might be viewed as an esoteric semantic problem except for the fact that many of the terms variously used by different authors carry with them implicit or explicit suggestions of underlying physiological mechanisms and even human-associated pathologies. In this article, we review several phenomena associated with diving and intermittent breathing, indicate the semantic issues arising from the use of each term, and make recommendations for best practice when applying specific terms to particular cardiorespiratory patterns. Ultimately, we emphasize that the biology-not the semantics-is what is important, but also stress that confusion surrounding underlying mechanisms can be avoided by more careful attention to terms describing physiological changes during intermittent breathing and diving.

Cardiorespiratory adaptations in small cetaceans and marine mammals.

The dive response, or the 'master switch of life', is probably the most studied physiological trait in marine mammals and is thought to conserve the available O2 for the heart and brain. Although generally thought to be an autonomic reflex, several studies indicate that the cardiovascular changes during diving are anticipatory and can be conditioned. The respiratory adaptations, where the aquatic breathing pattern resembles intermittent breathing in land mammals, with expiratory flow exceeding 160litres s-1 has been measured in cetaceans, and where exposure to extreme pressures results in alveolar collapse (atelectasis) and recruitment upon ascent. Cardiorespiratory coupling, where breathing results in changes in heart rate, has been proposed to improve gas exchange. Cardiorespiratory coupling has also been reported in marine mammals, and in the bottlenose dolphin, where it alters both heart rate and stroke volume. When accounting for this respiratory dependence on cardiac function, several studies have reported an absence of a diving-related bradycardia except during dives that exceed the duration that is fuelled by aerobic metabolism. This review summarizes what is known about the respiratory physiology in marine mammals, with a special focus on cetaceans. The cardiorespiratory coupling is reviewed, and the selective gas exchange hypothesis is summarized, which provides a testable mechanism for how breath-hold diving vertebrates may actively prevent uptake of N2 during routine dives, and how stress results in failure of this mechanism, which results in diving-related gas emboli.

Temperature effects on oxygen consumption and breathing pattern in juvenile and adult Chelonoidis carbonarius (Spix, 1824)

The effects of temperature on breathing pattern and oxygen consumption are being investigated in juvenile tortoises and compared to adults, in order to understand physiological adjustments of the respiratory system as related to body size, especially regarding the energetic expenditure associated with growth. We analyzed the breathing pattern and oxygen consumption of juvenile and adult red-footed tortoises (Chelonoidis carbonarius, Cryptodira: Testudinidae). The animals (N = 9; body mass ranging from 0.03 Kg to 2.5 Kg) were exposed to normoxic-normocarbic conditions using open respirometry in order to determine the breathing pattern and oxygen consumption in three different temperatures (15, 25, 35 °C). The obtained results showed intermittent breathing pattern in all tested temperatures in juveniles and adults. Tidal volume was not affected by changes in temperature, while breathing frequency increased significantly with increasing temperature, leading to a significant increment in minute ventilation between 15 and 35 °C. Mass specific oxygen consumption increased significantly with temperature and juveniles showed greater values when compared to adults. The alterations in the ventilatory response to temperature changes occurred in order to maintain the oxygen supply with increased metabolic activity. The differences between juveniles and adults in breathing frequency lead to juveniles needing a lower ventilation rate to perform gas exchange while extracting more oxygen. While these differences might be attributed to a greater metabolic expenditure during development, scaling effects on respiratory variables might be the main contributors to the found differences.

Mediastinal Migration of Standalone Cage-Plate Construct Following Multilevel Anterior Cervical Diskectomy and Fusion

Esophageal injury following anterior cervical spine surgery is a rare complication. In this interesting report, we present a 60-year-old male who presented with delayed dysphagia and intermittent breathing difficulty 20 months after multilevel anterior cervical diskectomy and fusion. Imaging revealed mediastinal migration of a standalone cage-plate construct near the adventitia of aortic arch along the fluid collection extending from upper cervical to the mediastinum. He underwent immediate washout, removal of loose hardware, and placement of a lower cervical esophageal stent and a gastrostomy tube. The patient is recovering well at last follow-up. This is the first report of delayed mediastinal migration of standalone cage-plate construct, to the best of our knowledge.

Нарушения дыхания во сне и БЛД-ассоциированная легочная гипертензия у недоношенных детей

This article presents current data on the features of sleep-related breathing disorders in preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension. The data on BPD-associated pulmonary hypertension, morphological changes in lung tissue, possible complications and clinical outcomes in this pathology were summarized. The basic data on intermittent hypoxic episodes, apnea and periodic breathing and their influence on the development and maintenance of pulmonary hypertension were reviewed. The methods were described that allow to accurately differentiate the character of sleep-related breathing disorders for the purpose of timely diagnosis and correction of therapy. The feasibility of using polysomnography and cardiorespiratory sleep monitoring as diagnostic methods for this category of patients was substantiated. Key words: BPD-associated pulmonary hypertension, breathing disorder, preterm infants

A review on the neuroprotective effects of hyperbaric oxygen therapy.

Hyperbaric oxygen therapy, intermittent breathing of 100% oxygen at a pressure upper than sea level, has been shown to be some of the neuroprotective effects and used therapeutically in a wide range of neurological disorders. This review summarizes current knowledge about the neuroprotective effects of hyperbaric oxygen therapy with their molecular mechanisms in different models of neurological disorders.

Antimicrobial effects of nitric oxide in murine models of Klebsiella pneumonia

RationaleInhalation of nitric oxide (NO) exerts selective pulmonary vasodilation. Nitric oxide also has an antimicrobial effect on a broad spectrum of pathogenic viruses, bacteria and fungi. ObjectivesThe aim of this study was to investigate the effect of inhaled NO on bacterial burden and disease outcome in a murine model of Klebsiella pneumonia. MethodsMice were infected with Klebsiella pneumoniae and inhaled either air alone, air mixed with constant levels of NO (at 80, 160, or 200 parts per million (ppm)) or air intermittently mixed with high dose NO (300 ppm). Forty-eight hours after airway inoculation, the number of viable bacteria in lung, spleen and blood was determined. The extent of infiltration of the lungs by inflammatory cells and the level of myeloperoxidase activity in the lungs were measured. Atomic force microscopy was used to investigate a possible mechanism by which nitric oxide exerts a bactericidal effect. Measurements and main resultsCompared to control animals infected with K. pneumoniae and breathed air alone, intermittent breathing of NO (300 ppm) reduced viable bacterial counts in lung and spleen tissue. Inhaled NO reduced infection-induced lung inflammation and improved overall survival of mice. NO destroyed the cell wall of K. pneumoniae and killed multiple-drug resistant K. pneumoniae in-vitro. ConclusionsIntermittent administration of high dose NO may be an effective approach to the treatment of pneumonia caused by K. pneumoniae.

Ventilation-perfusion heterogeneity measured by the multiple inert gas elimination technique is minimally affected by intermittent breathing of 100% O2.

Proton magnetic resonance (MR) imaging to quantify regional ventilation–perfusion ( V˙A/Q˙) ratios combines specific ventilation imaging (SVI) and separate proton density and perfusion measures into a composite map. Specific ventilation imaging exploits the paramagnetic properties of O2, which alters the local MR signal intensity, in an FIO2‐dependent manner. Specific ventilation imaging data are acquired during five wash‐in/wash‐out cycles of breathing 21% O2 alternating with 100% O2 over ~20 min. This technique assumes that alternating FIO2 does not affect V˙A/Q˙ heterogeneity, but this is unproven. We tested the hypothesis that alternating FIO2 exposure increases V˙A/Q˙ mismatch in nine patients with abnormal pulmonary gas exchange and increased V˙A/Q˙ mismatch using the multiple inert gas elimination technique (MIGET).The following data were acquired (a) breathing air (baseline), (b) breathing alternating air/100% O2 during an emulated‐SVI protocol (eSVI), and (c) 20 min after ambient air breathing (recovery). MIGET heterogeneity indices of shunt, deadspace, ventilation versus V˙A/Q˙ ratio, LogSD V˙, and perfusion versus V˙A/Q˙ ratio, LogSD Q˙ were calculated. LogSD V˙ was not different between eSVI and baseline (1.04 ± 0.39 baseline, 1.05 ± 0.38 eSVI, p = .84); but was reduced compared to baseline during recovery (0.97 ± 0.39, p = .04). There was no significant difference in LogSD Q˙ across conditions (0.81 ± 0.30 baseline, 0.79 ± 0.15 eSVI, 0.79 ± 0.20 recovery; p = .54); Deadspace was not significantly different (p = .54) but shunt showed a borderline increase during eSVI (1.0% ± 1.0 baseline, 2.6% ± 2.9 eSVI; p = .052) likely from altered hypoxic pulmonary vasoconstriction and/or absorption atelectasis. Intermittent breathing of 100% O2 does not substantially alter V˙A/Q˙ matching and if SVI measurements are made after perfusion measurements, any potential effects will be minimized.

Effects of unbalance on the nonlinear dynamics of rotors with transverse cracks

Unbalance is an inevitable issue in rotating machineries due to the manufacturing tolerances, the assembly errors, the damage in rotating components, etc. The effects of unbalance on the nonlinear dynamics of cracked rotors are investigated in this paper. In order to overcome the assumption of weight dominance, 3D finite element models are employed to discretize the rotor and several contact pairs are defined on the cracked surfaces to simulate the intermittent breathing behavior of crack. Then, the complex free interface component mode synthesis method (CMS) is employed to reduce the model’s order and to increase the computational efficiency. Finally, the obtained models are used to study the effects of concentrated and distributed unbalances on the nonlinear dynamic response of cracked rotors. The results show that the unbalance can significantly affect the breathing mechanism of crack and consequently dramatically change the rotor’s dynamic behaviors. Moreover, the different levels and orientations of unbalance lead to obviously different results. Besides, the responses of rotors with two asymmetric distributed unbalance are similar to those of rotors with a single concentrated unbalance though the rotors are overall balanced.

Blood lactate accumulation during competitive freediving and synchronized swimming

A number of competitive water sports are performed while breath-holding (apnea). Such performances put large demands on the anaerobic system, but the study of lactate accumulation in apneic sports is limited. We therefore aimed to determine and compare the net lactate accumulation (NLA) during competition events in six disciplines of competitive freediving (FD) and three disciplines of synchronized swimming (SSW). The FD disciplines were: static apnea (STA; n = 14); dynamic apnea (DYN; n = 19); dynamic apnea no fins (DNF; n = 16); constant weight (CWT; n = 12); constant weight no fins (CNF; n = 8); free immersion (FIM; n =10). The SSW disciplines were solo (n = 21), duet (n = 31) and team (n = 34). Capillary blood lactate concentration was measured before and three minutes after competition performances, and apneic duration and performance variables were recorded. In all nine disciplines NLA was observed. The highest mean (SD) NLA (mmol·L-1) was found in CNF at 6.3 (2.2), followed by CWT at 5.9 (2.3) and SSW solo at 5 (1.9). STA showed the lowest NLA 0.7 (0.7) mmol·L-1 compared to all other disciplines (P ⟨ 0.001). The NLA recorded shows that sports involving apnea involve high levels of anaerobic activity. The highest NLA was related to both work done by large muscle groups and long apneic periods, suggesting that NLA is influenced by both the type of work and apnea duration, with lower NLA in SSW due to shorter apneic episodes with intermittent breathing.

A Premature Baby’s Nursing Care Plan

Introduction: Baby T, is in the 46th day of his life has a 26-year-old mother who has suffered from about hypotyroid and preeclampsia during her pregnancy was born as a preterm baby when he was in 27 weeks’ gestation age by CS. Purpose: This article aimed to introduce the Nursing care plan. Materials and Methods: Place of work: Neonatal Intensive Care Unit/Balcali Research and Education Hospital in Adana, Turkey. Nursing Care Plan for the clinical period from 23.02.2015 till 11.03.2015. Informed consent was obtained from the baby’s family. Results: In addition to this, parents have blood incompatibility, therefore, such combinations of diseases impacted baby in the uterus and delivery happened earlier than expected date. His birth weight was 820 gr (0% - 5% percentile), height 34 cm (10% - 25% percentile), head-circumference 24 cm (10% percentile). The following healthcare needs were identified upon assessment; intubation, oxygene and stimulant support, monitorization, taking blood samples. Apical pulse is rapid and irregular within normal range 148 bpm, weight is 1605 gr, body is long, thin, limp with a slight potbelly. Initially suck/swallow reflex was absent/uncoordinated that’s why he was taking expressed breastmilk throughout orogastric catheter, it has started also oral giving for the couple of days with the development of sucking and swallowing. Reflexes depend on gestational age; rooting well established by 32 weeks’ gestation; coordinated reflexes for sucking, swallowing, and breathing usually established by 32 weeks; first component of Moro’s reflex (lateral extension of upper extremities with opening of hands) appears at 28 weeks; second two components (anterior flexion and audiblecry) appear at 32 weeks. Dubowitz examination indicates gestational age between 24 and 37 weeks. Consequently, this infant shows, palmar grasp, plantar grasp, moro reflex; the only response is the opening of the hand due to 27 gestational age. Apgar score was 4 - 7 (average, need oxygene and stimulant). Respiration was shallow, maintain neutral thermal environment, prevent or reduce risk of potential irregular, diaphragmatic with intermittent breathing 58/min. Conclusion: Nursing priorities should be promote optimal respiratory functioning, complications, maintain homeostasis, foster development of healthy family unit.

Analysis of the respiratory component of heart rate variability in the Cururu toad Rhinella schneideri

Beat-to-beat variation in heart rate (fH) has been used as a tool for elucidating the balance between sympathetic and parasympathetic modulation of the heart. A portion of the temporal changes in fH is evidenced by a respiratory influence (cardiorespiratory interaction) on heart rate variability (HRV) with heartbeats increasing and decreasing within a respiratory cycle. Nevertheless, little is known about respiratory effects on HRV in lower vertebrates. By using frequency domain analysis, we provide the first evidence of a ventilatory component in HRV similar to mammalian respiratory sinus arrhythmia in an amphibian, the toad Rhinella schneideri. Increases in the heartbeats arose synchronously with each lung inflation cycle, an intermittent breathing pattern comprised of a series of successive lung inflations. A well-marked peak in the HRV signal matching lung inflation cycle was verified in toads whenever lung inflation cycles exhibit a regular rhythm. The cardiac beat-to-beat variation evoked at the moment of lung inflation accounts for both vagal and sympathetic influences. This cardiorespiratory interaction may arise from interactions between central and peripheral feedback mechanisms governing cardiorespiratory control and may underlie important cardiorespiratory adjustments for gas exchange improvement especially under extreme conditions like low oxygen availability.

Role of vagus in mediating the toxicity induced by Mesobuthus tamulus venom in rats

Background: Mesobuthus tumulus (red scorpion, MBT) envenomation is a serious health problem in tropical countries and is responsible for high morbidity and mortality. Aims and Objectives: Earlier reports about the role of vagus in producing MBT venom-induced toxicity are conflicting. Therefore, in this study, the role of vagus in MBT venom-induced toxicity in rats was evaluated. Materials and Methods: The rats were divided into three groups. In group I, only saline was injected. This group served as control. In group II, MBT venom was injected. In group III, MBT venom was injected in vagotomized rats. Mean arterial pressure (MAP), ECG (for heart rate [HR]), respiratory rate, pulmonary water content, and survival time were determined in all groups. Results: Exposure to MBT venom in rats produced prolonged apnea with intermittent shallow breathing and was accompanied by an instantaneous decrease, followed by an increase and then a progressive decrease in MAP and HR leading to death within 60 min. There was increased pulmonary water content (82% vs. 74% in controls). MBT venom in vagotomized rats produced immediate changes as before, but these changes recovered to reasonably good level within 30 min and the animals survived for >120 min. Pulmonary water content in vagotomized rats was similar to control group. Conclusion: The results indicate that vagus plays a vital role for the toxic effects produced by MBT venom.

Acoustic Imaging of Clustered Rocket Nozzles Undergoing End Effects

A nonintrusive measure of the exhaust plume and immediate sound field produced by a cluster of two thrust-optimized parabolic contour nozzles is studied during two steady-state conditions. The first condition is at a nozzle pressure ratio of 25, at which point the flow is in a restricted-shock separated state. The second condition is at a nozzle pressure ratio of 37 and is when the flow and internal shock pattern transition rapidly between free-shock separated flow and the end-effects regime. These end-effects regime pulsations produce significant vibroacoustic loads due to the intermittent breathing of the last trapped annular separation bubble with the ambient. The exhaust plumes and surrounding sound field are first visualized by way of retroreflective shadowgraphy. Radon transforms of the spatially resolved shadowgraphy images are then used to characterize the statistical behavior of the acoustic wave fronts that reside within the hydrodynamic periphery of the nozzle flow. The findings reveal quantitative evidence of the sources of most intense vibroacoustic loads during the end-effects regime of clustered rockets.

Vagus nerve stimulator-induced apneas and hypopneas in a child with refractory seizures

Vagal nerve stimulators (VNS) can decrease seizure frequency in pediatric patients with refractory seizure disorders. However, vagal nerve stimulation can cause apneas and hypopneas during sleep, especially in patients with undiagnosed obstructive sleep apnea. We currently care for a young boy with cerebral palsy and refractory seizures. His mother noted intermittent noisy breathing and pauses in breathing at night following VNS implantation. An overnight sleep study revealed very abnormal sleep architecture and an apnea-hypopnea event rate of nine per h (18 per h when supine). After a review of the management options, the VNS was disabled. A repeat sleep study demonstrated improved sleep architecture and a reduced number of apneas and hypopneas (overall and supine event rate 1.7 per h). Management options in these patients include changing the VNS parameters, the use of positive airway pressure therapy, and discontinuing the VNS device.

Hypothyroidism-Associated Autoimmune Thyroiditis and Papillary Thyroid Cancer

Autoimmune thyroiditis (AI) and differentiated thyroid cancer as papillary type (PTC) are sometimes associated and several common pathogenic mechanisms have been described: BRAF mutations, hOGG1 loss of heterozygosity, interleukin-10 activation, selenoproteomas disturbances. Controversies are related to a more aggressive profile of PTC if AI is presented by interferences with oxidative stress and secondary carcinogenesis. This is a case report of a 37-year old female diagnosed a decade ago with multi-nodular goiter and hypothyroidism. She was treated in different endocrine centers. She started to accuse intermittent breathing difficulties which were not related to her previous diagnosis of asthma. On admission, the thyroid function was normal under levothyroxine (LT4) therapy with high anti-thyreoperoxidase antibodies levels of 1000 UI/mL (Normal<35) confirming AI. Thyroid ultrasound showed multiple nodules of 10 millimetres (mm), and a dominant one on the right lobe of 20 mm. Total thyroidectomy and lymph nodes dissection was performed. Pathological report confirmed AI and micro-PTC was identified (of 3 by 2 mm; T1N0M0). The thyroid scintigrame was negative when LT4 substitution was stopped and the blood thyroglobuline (TG) was very low (of 0.2 ng/mL) with negative anti-TG antibodies. A good outcome is estimated and no radioiodine ablative therapy was added only TSH suppressive doses of LT4. This case confirms that long standing autoimmune hypothyroidism might not protect of differentiated thyroid cancer but the papillary microcarcinoma display a good prognosis, in this particular situation based on small dimensions of the lesion and low levels of TG after surgery.

P98 – 3040: Early diagnosis of maple syrup urine disease (MSUD) by means of neonatal EEG and MRI in a newborn with encephalopathy

Objective Early diagnosis of maple syrup urine disease (MSUD) by means of neonatal EEG and MRI in a newborn with encephalopathy. Methods This male neonate was born after an uneventful pregnancy as the first child of non-consanguineous parents. Familial medical history is negative with respect to congenital defects, seizures or developmental delay. At day 9 he was referred to our center because of feeding problems, vomiting and lethargy. He progressively developed an encephalopathy with seizures, intermittent opisthotonic posturing and Kussmaul breathing. Elevated ammonia levels were detected in blood. EEG showed multifocal epileptic activity together with bursts of a monophasic negative theta rhythm (comb-like rhythm) in the rolandic and parasagittal regions. Brain imaging by MRI showed intramyelinic edema in the myelinated regions on Diffusion Weighted Images: cerebellar white matter, brainstem, posterior limb of internal capsule and both thalami. Results High ammonia levels are indicative for a metabolic encephalopathy. Monophasic negative theta rhythm on EEG, as well as intramyelinic edema on MRI are rare, but pathognomonic diagnostic clues for Maple Syrup Urine Disease (OMIM: 24800). MSUD is a disorder of the branched-chain amino-acid metabolism leading to a progressive neonatal encephalopathy. Early presenting symptoms are aspecific, including feeding problems, vomiting, lethargy, opisthotonic posturing and seizures. Accumulation of the leukotoxic metabolites (2-ketoacids and branched-chain amino acids leucine, valine and isoleucine) finally leads to coma and central respiratory failure, which can be prevented by dietary measures. Conclusion Neonatal encephalopathy and neonatal seizures require comprehensive diagnostic measures, comprising a full metabolic blood screen, longitudinal neurophysiological monitoring and brain imaging, preferably by means of MRI. Electroencephalographic and MRI features typical for MSUD have been rarely reported together. Based on this case report, we discuss the unique EEG pattern before and after MSUD treatment.

Ontogeny and control of the heart rate power spectrum in the last third of gestation in fetal sheep

Power spectral analysis of fetal heart rate variability has been proposed to provide a non-invasive estimate of autonomic balance. However, there are few systematic data before birth. We therefore examined developmental changes in the frequency power spectrum at very low (0-0.04 Hz), low (0.04-0.15 Hz) and high frequencies (0.15-0.4 Hz), as well as the ratio of low- to high-frequency power (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n = 8), 0.7 (n = 7) and 0.8 gestational age (ga; n = 11). In a second study, 0.8 ga fetuses received either atropine (4.8 mg bolus, then 4.8 mg h(-1) for 30 min, n = 6) or 6-hydroxydopamine (20 mg ml(-1) at 2.5 ml h(-1) for 3 h; n = 9). Data were analysed by sleep state, defined by low-voltage-high-frequency (LV) or high-voltage-low-frequency (HV) EEG. Total spectral power increased with gestational age (P < 0.05), while LF/HF decreased from 0.6 to 0.7 ga. At 0.8 ga, heart rate and LF/HF were significantly higher during HV than LV sleep (P < 0.05). Consistent with this, although total spectral power was not significantly greater during HV sleep, there was a significant interaction between sleep state and frequency band (P = 0.02). Both atropine (P = 0.05) and 6-hydroxydopamine (P < 0.05) were associated with an overall reduction in spectral power but no significant effect on the LF/HF ratio. This study does not support substantial, consistent differences between the frequencies of sympathetic and parasympathetic activity in late-gestation fetal sheep.

Pulsed high oxygen induces a hypoxic-like response in human umbilical endothelial cells and in humans

It has been proposed that relative changes of oxygen availability, rather than steady-state hypoxic or hyperoxic conditions, play an important role in hypoxia-inducible factor (HIF) transcriptional effects. According to this hypothesis describing the "normobaric oxygen paradox", normoxia following a hyperoxic event is sensed by tissues as an oxygen shortage, upregulating HIF-1 activity. With the aim of confirming, at cellular and at functional level, that normoxia following a hyperoxic event is "interpreted" as a hypoxic event, we report a combination of experiments addressing the effects of an intermittent increase of oxygen concentration on HIF-1 levels and the activity level of specific oxygen-modulated proteins in cultured human umbilical vein endothelial cells and the effects of hemoglobin levels after intermittent breathing of normobaric high (100%) and low (15%) oxygen in vivo in humans. Our experiments confirm that, during recovery after hyperoxia, an increase of HIF expression occurs in human umbilical vein endothelial cells, associated with an increase of matrix metalloproteinases activity. These data suggest that endothelial cells "interpret" the return to normoxia after hyperoxia as a hypoxic stimulus. At functional level, our data show that breathing both 15 and 100% oxygen 30 min every other day for a period of 10 days induces an increase of hemoglobin levels in humans. This effect was enhanced after the cessation of the oxygen breathing. These results indicate that a sudden decrease in tissue oxygen tension after hyperoxia may act as a trigger for erythropoietin synthesis, thus corroborating the hypothesis that "relative" hypoxia is a potent stimulator of HIF-mediated gene expressions.