Convective Oxygen Research Articles

Higher oxygen content and transport characterize high-altitude ethnic Tibetan women with the highest lifetime reproductive success

We chose the "natural laboratory" provided by high-altitude native ethnic Tibetan women who had completed childbearing to examine the hypothesis that multiple oxygen delivery traits were associated with lifetime reproductive success and had genomic associations. Four hundred seventeen (417) women aged 46 to 86 y residing at ≥3,500 m in Upper Mustang, Nepal, provided information on reproductive histories, sociocultural factors, physiological measurements, and DNA samples for this observational cohort study. Simultaneously assessing multiple traits identified combinations associated with lifetime reproductive success measured as the number of livebirths. Women with the most livebirths had distinctive hematological and cardiovascular traits. A hemoglobin concentration near the sample mode and a high percent of oxygen saturation of hemoglobin raised arterial oxygen concentration without risking elevated blood viscosity. We propose ongoing stabilizing selection on hemoglobin concentration because extreme values predicted fewer livebirths and directional selection favoring higher oxygen saturation because higher values had more predicted livebirths. EPAS1, an oxygen homeostasis locus with strong signals of positive natural selection and a high frequency of variants occurring only among populations indigenous to the Tibetan Plateau, associated with hemoglobin concentration. High blood flow into the lungs, wide left ventricles, and low hypoxic heart rate responses aided effective convective oxygen transport to tissues. Women with physiologies closer to unstressed, low altitude values had the highest lifetime reproductive success. This example of ethnic Tibetan women residing at high altitudes in Nepal links reproductive fitness with trait combinations increasing oxygen delivery under severe hypoxic stress and demonstrates ongoing natural selection.

Measuring maximum heart rate to study cardiac thermal performance and heat tolerance in fishes.

The thermal sensitivity of heart rate (fH) in fishes has fascinated comparative physiologists for well over a century. We now know that elevating fH is the primary mechanism through which fishes increase convective oxygen delivery during warming to meet the concomitant rise in tissue oxygen consumption. Thus, limits on fH can constrain whole-animal aerobic metabolism. In this Review, we discuss an increasingly popular methodology to study these limits, the measurement of pharmacologically induced maximum fH (fH,max) during acute warming of an anaesthetized fish. During acute warming, fH,max increases exponentially over moderate temperatures (Q10∼2-3), but this response is blunted with further warming (Q10∼1-2), with fH,max ultimately reaching a peak (Q10≤1) and the heartbeat becoming arrhythmic. Because the temperatures at which these transitions occur commonly align with whole-animal optimum and critical temperatures (e.g. aerobic scope and the critical thermal maximum), they can be valuable indicators of thermal performance. The method can be performed simultaneously on multiple individuals over a few hours and across a broad size range (<1 to >6000 g) with compact equipment. This simplicity and high throughput make it tractable in lab and field settings and enable large experimental designs that would otherwise be impractical. As with all reductionist approaches, the method does have limitations. Namely, it requires anaesthesia and pharmacological removal of extrinsic cardiac regulation. Nonetheless, the method has proven particularly effective in the study of patterns and limits of thermal plasticity and holds promise for helping to predict and mitigate outcomes of environmental change.

3D simulations of magnetoconvection in a rapidly rotating supernova progenitor

ABSTRACT We present a first 3D magnetohydrodynamic (MHD) simulation of oxygen, neon, and carbon shell burning in a rapidly rotating $16\hbox{-}\mathrm{M}_\odot$ core-collapse supernova progenitor. We also run a purely hydrodynamic simulation for comparison. After $\mathord \approx 180\mathrm{s}$ ($\mathord \approx$ 15 and 7 convective turnovers, respectively), the magnetic fields in the oxygen and neon shells achieve saturation at 1011 and 5 × 1010 G. The strong Maxwell stresses become comparable to the radial Reynolds stresses and eventually suppress convection. The suppression of mixing by convection and shear instabilities results in the depletion of fuel at the base of the burning regions, so that the burning shell eventually move outward to cooler regions, thus reducing the energy generation rate. The strong magnetic fields efficiently transport angular momentum outwards, quickly spinning down the rapidly rotating convective oxygen and neon shells and forcing them into rigid rotation. The hydrodynamic model shows complicated redistribution of angular momentum and develops regions of retrograde rotation at the base of the convective shells. We discuss implications of our results for stellar evolution and for the subsequent core-collapse supernova. The rapid redistribution of angular momentum in the MHD model casts some doubt on the possibility of retaining significant core angular momentum for explosions driven by millisecond magnetars. However, findings from multidimensional models remain tentative until stellar evolution calculations can provide more consistent rotation profiles and estimates of magnetic field strengths to initialize multidimensional simulations without substantial numerical transients. We also stress the need for longer simulations, resolution studies, and an investigation of non-ideal effects.

Physiological Responses to Exercise in Hypoxia in Preterm Adults: Convective and Diffusive Limitations in the O 2 Transport.

Premature birth induces long-term sequelae on the cardiopulmonary system, leading to reduced exercise capacity. However, the mechanisms of this functional impairment during incremental exercise remain unclear. Also, a blunted hypoxic ventilatory response was found in preterm adults, suggesting an increased risk for adverse effects of hypoxia in this population. This study aimed to investigate the oxygen cascade during incremental exercise to exhaustion in both normoxia and hypobaric hypoxia in prematurely born adults with normal lung function and their term born counterparts. Noninvasive measures of gas exchange, cardiac hemodynamics, and both muscle and cerebral oxygenation were continuously performed using metabolic cart, transthoracic impedance, and near-infrared spectroscopy, respectively, during an incremental exercise test to exhaustion performed at sea level and after 3 d of high-altitude exposure in healthy preterm ( n = 17; gestational age, 29 ± 1 wk; normal lung function) and term born ( n = 17) adults. At peak, power output, oxygen uptake, stroke volume indexed for body surface area, and cardiac output were lower in preterm compared with term born in normoxia ( P = 0.042, P = 0.027, P = 0.030, and P = 0.018, respectively) but not in hypoxia, whereas pulmonary ventilation, peripheral oxygen saturation, and muscle and cerebral oxygenation were similar between groups. These later parameters were modified by hypoxia ( P < 0.001). Hypoxia increased muscle oxygen extraction at submaximal and maximal intensity in term born ( P < 0.05) but not in preterm participants. Hypoxia decreased cerebral oxygen saturation in term born but not in preterm adults at rest and during exercise ( P < 0.05). Convective oxygen delivery was decreased by hypoxia in term born ( P < 0.001) but not preterm adults, whereas diffusive oxygen transport decreased similarly in both groups ( P < 0.001 and P < 0.001, respectively). These results suggest that exercise capacity in preterm is primarily reduced by impaired convective, rather than diffusive, oxygen transport. Moreover, healthy preterm adults may experience blunted hypoxia-induced impairments during maximal exercise compared with their term counterparts.

Critical conditions at liftoff limit of a laminar n-butane-air jet diffusion flame

The stability mechanism of laminar coflow jet diffusion flames in normal gravity has been studied computationally and experimentally. N-butane, the heaviest alkane in a gaseous state at ambient temperature and pressure, is used as the fuel since the reaction mechanism is similar to that of higher (liquid) hydrocarbons. The critical mean n-butane jet and coflowing air velocities at flame stability limits are measured using a small fuel tube burner (0.8 mm inner diameter). The time-dependent, axisymmetric numerical code with a detailed reaction mechanism (58 species and 540 reactions), molecular diffusive transport, and a radiation model, reveals a flame structure. A fuel-lean peak reactivity spot (i.e., reaction kernel), possessing the hybrid nature of diffusion-premixed flame structure at a constant temperature of ≈1560 K, is formed at the flame base and controls the flame stability. In a near-quiescent environment, the flame base resides below the fuel tube exit plane and thereby premixing is limited. As the coflowing air velocity is increased incrementally under a fixed fuel jet velocity, the flame base moves slightly above (≈1 mm) the burner exit and vigorous premixed combustion becomes prevailing. The local heat-release rate at the reaction kernel nearly doubles due to the increased convective oxygen flux (i.e., a blowing effect). The local Damköhler number, newly defined as a ratio of the square root of the local heat-release rate and the local velocity, decreases gradually first and drops abruptly at a critical threshold value and the flame base lifts off from the burner rim. The calculated coflow air velocity at liftoff is ≈0.38 m/s at the fuel jet velocity of 2 m/s, which is consistent with an extrapolated measured value of 0.41 m/s. This work has determined the critical Damköhler number at the stability limit quantitatively, for the first time, for laminar jet diffusion flames.

MO582: Impaired HIF-1 Regulation in Skeletal Muscle of Patients With Advanced-Stage Chronic Kidney Disease

Abstract BACKGROUND AND AIMS Tiredness and fatigue are common symptoms in patients with chronic kidney disease (CKD), but their underlying mechanisms are unknown and treatments unavailable. Patients with CKD display abnormalities along the entire oxygen cascade, with impaired diffusive and convective oxygen transport, thus contributing to a reduced tissue oxygen supply. Hypoxic adaptation is largely regulated by hypoxia-inducible factor 1 (HIF-1α), encoded by the HIF-1Α gene [1], and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α). In response to hypoxia or anemia, the muscle HIF-1α target genes increase oxygen transport through angiogenesis, responsiveness to insulin, cell proliferation and apoptosis/survival [2]. PGC-1α controls the expression of genes involved in mitochondrial biogenesis, energy homeostasis and glucose metabolism. PGC-1α is correlated with a total-body aerobic capacity [3], and its decrease has been detected in muscles of elderly persons and type 2 diabetes patients [3,4]. We hypothesized that desensitization of the HIF-1α driven oxygen-sensing mechanisms occurs in CKD patients. METHOD HIF-1α, PGC1α gene and protein expression, studied by Rt–PCR and immunohistochemistry, were assessed in the rectus abdominis muscle biopsies from 31 CKD patients with non-dialysis CKD 5 (18 M/13 F, eGFR 8 ± 1 mL/min) and were compared with those obtained in 10 subjects with normal renal function (7M/3F). HIF-1α, PGC1α expression was studied also in C2C12 myotubes exposed to 10% normal serum or uremic serum (US) for 48 h. In addition, mitofusin-2 (MFN2), nuclear factor erythroid 2-related factor 2 (NRF2), and oxidative phosphorylation (OXPHOS) related to mitochondria integrity were monitored by Rt–PCR and/or western blot. Changes in the membrane potential were quantified by JC1 staining and fluorimeter analysis. RESULTS Despite anemia (Hb 9.5 ± 1 g/dL), HIF-1α mRNA was severely blunted in the muscle of CKD patients, as well as PGC1α that resulted down-regulated in 62.5% of them (P &amp;lt; 0.05) (Fig. 1). Log HIF-1α mRNA was directly related to log eGFR (r = 0.632, P &amp;lt; 0.02), suggesting that the hypoxic response in muscle progressively down-regulates as the renal function declines. In cultured myotubes, US decreases PGC1α, HIF1α, MFN2, NRF2 and OXPHOS and membrane potential (P &amp;lt; 0.05–0.01). CONCLUSION In patients with non-dialysis CKD, PGC1α and HIF1α are down-regulated, as well as in an in vitro model that resembles the uremic milieu. On the one hand, these findings are in keeping with impaired oxidative metabolism in the advanced stage of CKD, while on the other hand, they may account for the fatigue often referred by these patients. Moreover, our study suggests that the HIF prolyl hydroxylase inhibitor (HIF-PHIs), currently in clinical development, might be targeted on muscle metabolism and function and tested in the treatment of myopathy and fatigue in CKD.

Global Reach 2018: sympathetic neural and hemodynamic responses to submaximal exercise in Andeans with and without chronic mountain sickness.

Andeans with chronic mountain sickness (CMS) and polycythemia have similar maximal oxygen uptakes to healthy Andeans. Therefore, this study aimed to explore potential adaptations in convective oxygen transport, with a specific focus on sympathetically mediated vasoconstriction of nonactive skeletal muscle. In Andeans with (CMS+, n = 7) and without (CMS-, n = 9) CMS, we measured components of convective oxygen delivery, hemodynamic (arterial blood pressure via intra-arterial catheter), and autonomic responses [muscle sympathetic nerve activity (MSNA)] at rest and during steady-state submaximal cycling exercise [30% and 60% peak power output (PPO) for 5 min each]. Cycling caused similar increases in heart rate, cardiac output, and oxygen delivery at both workloads between both Andean groups. However, at 60% PPO, CMS+ had a blunted reduction in Δtotal peripheral resistance (CMS-, -10.7 ± 3.8 vs. CMS+, -4.9 ± 4.1 mmHg·L-1·min-1; P = 0.012; d = 1.5) that coincided with a greater Δforearm vasoconstriction (CMS-, -0.2 ± 0.6 vs. CMS+, 1.5 ± 1.3 mmHg·mL-1·min-1; P = 0.008; d = 1.7) and a rise in Δdiastolic blood pressure (CMS-, 14.2 ± 7.2 vs. CMS+, 21.6 ± 4.2 mmHg; P = 0.023; d = 1.2) compared with CMS-. Interestingly, although MSNA burst frequency did not change at 30% or 60% of PPO in either group, at 60% Δburst incidence was attenuated in CMS+ (P = 0.028; d = 1.4). These findings indicate that in Andeans with polycythemia, light intensity exercise elicited similar cardiovascular and autonomic responses compared with CMS-. Furthermore, convective oxygen delivery is maintained during moderate-intensity exercise despite higher peripheral resistance. In addition, the elevated peripheral resistance during exercise was not mediated by greater sympathetic neural outflow, thus other neural and/or nonneural factors are perhaps involved.NEW & NOTEWORTHY During submaximal exercise, convective oxygen transport is maintained in Andeans suffering from polycythemia. Light intensity exercise elicited similar cardiovascular and autonomic responses compared with healthy Andeans. However, during moderate-intensity exercise, we observed a blunted reduction in total peripheral resistance, which cannot be ascribed to an exaggerated increase in muscle sympathetic nerve activity, indicating possible contributions from other neural and/or nonneural mechanisms.

The effect of the protective face mask on cardiorespiratory response during aerobic exercise.

The protective face mask (PFM) has been widely used for safety purposes and, after the advent of the COVID-19 pandemic, its use is growing steadily, not only among healthcare personnel but also the general population. While the PFM is important to preserve the wearer from contaminating agents present in the airflow, they are well known to increase the subjective perception of breathing difficulty. Although some studies have demonstrated that PFM use worsens exercise tolerance, several studies state that there is no such limitation with the use of PFM. Moreover, no serious adverse effects during physical exercise have been found in the literature. Physical exercise represents a significant challenge to the human body through a series of integrated changes in function that involve most of its physiologic systems. In this respect, cardiovascular and respiratory systems provide the capacity to sustain physical tasks over extended periods. Within this scenario, both convective oxygen (O2 ) transport (product of arterial O2 content×blood flow) to the working locomotor muscles and O2 diffusive transport from muscle capillaries to mitochondria are of paramount importance to endurance performance. Interestingly, the effects of PFM on cardiorespiratory response during aerobic exercise depends on the type of mask and exercise (i.e., walking, running, or cycling), the ventilatory demands, arterial oxygen levels, maximal oxygen consumption and endurance performance. The purpose of this review is to elucidate the effect of protective face mask-wearing on (1) cardiorespiratory responses during aerobic exercise and (2) endurance performance.

New Applications of HBOC-201: A 25-Year Review of the Literature.

If not cured promptly, tissue ischemia and hypoxia can cause serious consequences or even threaten the life of the patient. Hemoglobin-based oxygen carrier-201 (HBOC-201), bovine hemoglobin polymerized by glutaraldehyde and stored in a modified Ringer's lactic acid solution, has been investigated as a blood substitute for clinical use. HBOC-201 was approved in South Africa in 2001 to treat patients with low hemoglobin (Hb) levels when red blood cells (RBCs) are contraindicated, rejected, or unavailable. By promoting oxygen diffusion and convective oxygen delivery, HBOC-201 may act as a direct oxygen donor and increase oxygen transfer between RBCs and between RBCs and tissues. Therefore, HBOC-201 is gradually finding applications in treating various ischemic and hypoxic diseases including traumatic hemorrhagic shock, hemolysis, myocardial infarction, cardiopulmonary bypass, perioperative period, organ transplantation, etc. However, side effects such as vasoconstriction and elevated methemoglobin caused by HBOC-201 are major concerns in clinical applications because Hbs are not encapsulated by cell membranes. This study summarizes preclinical and clinical studies of HBOC-201 applied in various clinical scenarios, outlines the relevant mechanisms, highlights potential side effects and solutions, and discusses the application prospects. Randomized trials with large samples need to be further studied to better validate the efficacy, safety, and tolerability of HBOC-201 to the extent where patient-specific treatment strategies would be developed for various clinical scenarios to improve clinical outcomes.

Differential rotation in a 3D simulation of oxygen shell burning

ABSTRACTWe study differential rotation in late-stage shell convection in a 3D hydrodynamic simulation of a rapidly rotating $16\, {\rm M}_{\odot }$ helium star with a particular focus on the convective oxygen shell. We find that the oxygen shell develops a quasi-stationary pattern of differential rotation that is described neither by uniform angular velocity as assumed in current stellar evolution models of supernova progenitors, nor by uniform specific angular momentum. Instead, the oxygen shell develops a positive angular velocity gradient with faster rotation at the equator than at the pole by tens of per cent. We show that the angular momentum transport inside the convection zone is not adequately captured by a diffusive mixing-length flux proportional to the angular velocity or angular momentum gradient. Zonal flow averages reveal stable large-scale meridional flow and an entropy deficit near the equator that mirrors the patterns in the angular velocity. The structure of the flow is reminiscent of simulations of stellar surface convection zones and the differential rotation of the Sun, suggesting that similar effects are involved; future simulations will need to address in more detail how the interplay of buoyancy, inertial forces, and turbulent stresses shapes differential rotation during late-stage convection in massive stars. If convective regions develop positive angular velocity gradients, angular momentum could be shuffled out of the core region more efficiently, potentially making the formation of millisecond magnetars more difficult. Our findings have implications for neutron star birth spin periods and supernova explosion scenarios that involve rapid core rotation.

Selection pressure at altitude for genes related to alcohol metabolism: A role for endogenous enteric ethanol synthesis?

What is the topic of this review? Highland natives have undergone natural selection for genetic variants advantageous in adaptation to the hypobaric hypoxia experienced at high altitude. Why genes related to alcohol metabolism appear consistently selected for has not been greatly considered. We hypothesize that altitude-related changes in the gut microbiome offer one possible explanation. What advances does it highlight? Low intestinal oxygen tension might favour the production of ethanol through anaerobic fermentation by the gut microbiome. Subsequent increases in endogenous ethanol absorption could therefore provide a selection pressure for gene variants favouring its increased degradation, or perhaps reduced degradation if endogenously synthesized ethanol acts as a metabolic signalling molecule. Reduced tissue availability of oxygen results from ascent to high altitude, where atmospheric pressure, and thus the partial pressure of inspired oxygen, fall (hypobaric hypoxia). In humans, adaptation to such hypoxia is necessary for survival. These functional changes remain incompletely characterized, although metabolic adaptation (rather than simple increases in convective oxygen delivery) appears to play a fundamental role. Those populations that have remained native to high altitude have undergone natural selection for genetic variants associated with advantageous phenotypic traits. Interestingly, a consistent genetic signal has implicated alcohol metabolism in the human adaptive response to hypobaric hypoxia. The reasons for this remain unclear. One possibility is that increased alcohol synthesis occurs through fermentation by gut bacteria in response to enteric hypoxia. There is growing evidence that anaerobes capable of producing ethanol become increasingly prevalent with high-altitude exposure. We hypothesize that: (1) ascent to high altitude renders the gut luminal environment increasingly hypoxic, favouring (2) an increase in the population of enteric fermenting anaerobes, hence (3) the synthesis of alcohol which, through systemic absorption, leads to (4) selection pressure on genes relating to alcohol metabolism. In theory, alcohol could be viewed as a toxic product, leading to selection of gene variants favouring its metabolism. On the contrary, alcohol is a metabolic substrate that might be beneficial. This mechanism could also account for some of the interindividual differences of lowlanders in acclimatization to altitude. Future research should be aimed at determining any shifts to favour ethanol-producing anaerobes after ascent to altitude.

3D simulations of oxygen shell burning with and without magnetic fields.

We present a first 3D magnetohydrodynamic (MHD) simulation of convective oxygen and neon shell burning in a non-rotating [Formula: see text] star shortly before core collapse to study the generation of magnetic fields in supernova progenitors. We also run a purely hydrodynamic control simulation to gauge the impact of the magnetic fields on the convective flow and on convective boundary mixing. After about 17 convective turnover times, the magnetic field is approaching saturation levels in the oxygen shell with an average field strength of [Formula: see text], and does not reach kinetic equipartition. The field remains dominated by small-to-medium scales, and the dipole field strength at the base of the oxygen shell is only [Formula: see text]. The angle-averaged diagonal components of the Maxwell stress tensor mirror those of the Reynolds stress tensor, but are about one order of magnitude smaller. The shear flow at the oxygen-neon shell interface creates relatively strong fields parallel to the convective boundary, which noticeably inhibit the turbulent entrainment of neon into the oxygen shell. The reduced ingestion of neon lowers the nuclear energy generation rate in the oxygen shell and thereby slightly slows down the convective flow. Aside from this indirect effect, we find that magnetic fields do not appreciably alter the flow inside the oxygen shell. We discuss the implications of our results for the subsequent core-collapse supernova and stress the need for longer simulations, resolution studies, and an investigation of non-ideal effects for a better understanding of magnetic fields in supernova progenitors.

Anisotropy and porosity as factors of fluctuations in exothermic processes during grain storage

Scientific-based assessment and management of the state of stored grain based on reliable information provides a reliable forecast of the direction of interrelated physical, chemical and biochemical processes in order to take timely measures to prevent quantitative and qualitative losses and food safety of grain. Based on the stationary nature of the grain storage process, it is proposed to use a system of differential equations describing the conditions of heat transfer by convective transfer, thermal conductivity, and oxygen diffusion through a layer of anisotropic, porous material to prevent self-heating of the grain. The level of the activation barrier Eа=123 kJ/mol of the grain mass is established as a thermodynamic system, when it reaches a stable internal heat source. To take into account the main factors and forecast possible exothermic processes in the grain mass (on currents, in elevators, during transportation, storage, etc.), it is proposed.

Exercise training in COPD: muscle O2 transport plasticity.

Both convective oxygen (O2) transport to, and diffusive transport within, skeletal muscle are markedly diminished in patients with COPD. However, it is unknown how these determinants of peak muscle O2 uptake (V'mO2peak) respond to exercise training in patients with COPD. Therefore, the purpose of this study was to assess the plasticity of skeletal muscle O2 transport determinants of V'mO2peak in patients with COPD.Adaptations to 8 weeks of single-leg knee-extensor exercise training were measured in eight patients with severe COPD (mean±sem forced expiratory volume in 1 s (FEV1) 0.9±0.1 L) and eight healthy, well-matched controls. Femoral arterial and venous blood samples, and thermodilution-assessed leg blood flow were used to determine muscle O2 transport and utilisation at maximal exercise pre- and post-training.Training increased V'mO2peak in both COPD (by ∼26% from 271±29 to 342±35 mL·min-1) and controls (by ∼32% from 418±37 to 553±41 mL·min-1), restoring V'mO2peak in COPD to only ∼80% of pre-training control V'mO2peak Muscle diffusive O2 transport increased similarly in both COPD (by ∼38% from 6.6±0.9 to 9.1±0.9 mL·min-1·mmHg-1) and controls (by ∼36% from 10.4±0.7 to 14.1±0.8 mL·min-1·mmHg-1), with the patients reaching ∼90% of pre-training control values. In contrast, muscle convective O2 transport increased significantly only in controls (by ∼26% from 688±57 to 865±69 mL·min-1), leaving patients with COPD (438±45 versus 491±51 mL·min-1) at ∼70% of pre-training control values.While muscle diffusive O2 transport in COPD was largely restored by exercise training, V'mO2peak remained constrained by limited plasticity in muscle convective O2 transport.

The oxygen cascade in patients treated with hemodialysis and native high-altitude dwellers: lessons from extreme physiology to benefit patients with end-stage renal disease.

Patients treated with hemodialysis (HD) repeatedly undergo intradialytic low arterial oxygen saturation and low central venous oxygen saturation, reflecting an imbalance between upper body systemic oxygen supply and demand, which are associated with increased mortality. Abnormalities along the entire oxygen cascade, with impaired diffusive and convective oxygen transport, contribute to the reduced tissue oxygen supply. HD treatment impairs pulmonary gas exchange and reduces ventilatory drive, whereas ultrafiltration can reduce tissue perfusion due to a decline in cardiac output. In addition to these factors, capillary rarefaction and reduced mitochondrial efficacy can further affect the balance between cellular oxygen supply and demand. Whereas it has been convincingly demonstrated that a reduced perfusion of heart and brain during HD contributes to organ damage, the significance of systemic hypoxia remains uncertain, although it may contribute to oxidative stress, systemic inflammation, and accelerated senescence. These abnormalities along the oxygen cascade of patients treated with HD appear to be diametrically opposite to the situation in Tibetan highlanders and Sherpa, whose physiology adapted to the inescapable hypobaric hypoxia of their living environment over many generations. Their adaptation includes pulmonary, vascular, and metabolic alterations with enhanced capillary density, nitric oxide production, and mitochondrial efficacy without oxidative stress. Improving the tissue oxygen supply in patients treated with HD depends primarily on preventing hemodynamic instability by increasing dialysis time/frequency or prescribing cool dialysis. Whether dietary or pharmacological interventions, such as the administration of L-arginine, fermented food, nitrate, nuclear factor erythroid 2-related factor 2 agonists, or prolyl hydroxylase 2 inhibitors, improve clinical outcome in patients treated with HD warrants future research.

Effects of impaired microvascular flow regulation on metabolism-perfusion matching and organ function.

Impaired tissue oxygen delivery is a major cause of organ damage and failure in critically ill patients, which can occur even when systemic parameters, including cardiac output and arterial hemoglobin saturation, are close to normal. This review addresses oxygen transport mechanisms at the microcirculatory scale, and how hypoxia may occur in spite of adequate convective oxygen supply. The structure of the microcirculation is intrinsically heterogeneous, with wide variations in vessel diameters and flow pathway lengths, and consequently also in blood flow rates and oxygen levels. The dynamic processes of structural adaptation and flow regulation continually adjust microvessel diameters to compensate for heterogeneity, redistributing flow according to metabolic needs to ensure adequate tissue oxygenation. A key role in flow regulation is played by conducted responses, which are generated and propagated by endothelial cells and signal upstream arterioles to dilate in response to local hypoxia. Several pathophysiological conditions can impair local flow regulation, causing hypoxia and tissue damage leading to organ failure. Therapeutic measures targeted to systemic parameters may not address or may even worsen tissue oxygenation at the microvascular level. Restoration of tissue oxygenation in critically ill patients may depend on restoration of endothelial cell function, including conducted responses.

Quantitative analysis of trapezoid baffle block sloping angles on oxygen transport and performance of proton exchange membrane fuel cell

Increasing the power density of proton exchange membrane (PEM) fuel cell without extra cost through flow channel design is an effective method to achieve cost and compact requirement of its commercialization for vehicles. PEM fuel cell power or current density is mainly limited by oxygen transport to the reacting sites in the cathode porous electrode. Inserting baffle blocks in the flow channel of PEM fuel cell can effectively enhance the oxygen transport and fuel cell performance. However, existing researches on the structure design of baffle blocks are still insufficient, especially for the design of baffle block sloping angles. In this study, the influence of the trapezoid baffle block sloping angles on the convective and diffusive oxygen transport and performance of PEM fuel cell is quantitatively investigated using a three-dimensional numerical model. The results indicate that larger leading angle of the baffle block leads to a higher gas velocity component in the vertical direction, hence enhances the convective oxygen transport effect; but it reduces the convection area, as well as the oxygen delivery efficiency in the channel. Larger trailing angle of the baffle block induces the back-flow phenomenon at the rear of the baffle block, which causes the loss of gas pressure and worse oxygen transport. Both the baffle block sloping angles are carefully designed, and it demonstrates that the trapezoid baffle blocks with both the leading and trailing sloping angles of 45° show the best oxygen transport and fuel cell performance.

Training with blood flow restriction increases femoral artery diameter and thigh oxygen delivery during knee-extensor exercise in recreationally trained men.

Endurance-type training with blood flow restriction (BFR) increases maximum oxygen uptake ( ) and exercise endurance of humans. However, the physiological mechanisms behind this phenomenon remain uncertain. In the present study, we show that BFR-interval training reduces the peripheral resistance to oxygen transport during dynamic, submaximal exercise in recreationally-trained men, mainly by increasing convective oxygen delivery to contracting muscles. Accordingly, BFR-training increased oxygen uptake by, and concomitantly reduced net lactate release from, the contracting muscles during relative-intensity-matched exercise, at the same time as invoking a similar increase in diffusional oxygen conductance compared to the training control. Only BFR-training increased resting femoral artery diameter, whereas increases in oxygen transport and uptake were dissociated from changes in the skeletal muscle content of mitochondrial electron-transport proteins. Thus, physically trained men benefit from BFR-interval training by increasing leg convective oxygen transport and reducing lactate release, thereby improving the potential for increasing the percentage of that can be sustained throughout exercise. In the present study, we investigated the effect of training with blood flow restriction (BFR) on thigh oxygen transport and uptake, and lactate release, during exercise. Ten recreationally-trained men (50±5mLkg-1 min-1 ) completed 6weeks of interval cycling with one leg under BFR (BFR-leg; pressure: ∼180mmHg) and the other leg without BFR (CON-leg). Before and after the training intervention (INT), thigh oxygen delivery, extraction, uptake, diffusion capacity and lactate release were determined during knee-extensor exercise at 25% incremental peak power output (iPPO) (Ex1), followed by exercise to exhaustion at 90% pre-training iPPO (Ex2), by measurement of femoral-artery blood flow and femoral-arterial and -venous blood sampling. A muscle biopsy was obtained from legs before and after INT to determine mitochondrial electron-transport protein content. Femoral-artery diameter was also measured. In the BFR-leg, after INT, oxygen delivery and uptake were higher, and net lactate release was lower, during Ex1 (vs. CON-leg; P<0.05), with an 11% larger increase in workload (vs. CON-leg; P<0.05). During Ex2, after INT, oxygen delivery was higher, and oxygen extraction was lower, in the BFR-leg compared to the CON-leg (P<0.05), resulting in an unaltered oxygen uptake (vs. CON-leg; P>0.05). In the CON-leg, at both intensities, oxygen delivery, extraction, uptake and lactate release remained unchanged (P>0.05). Resting femoral artery diameter increased with INT only in the BFR-leg (∼4%; P<0.05). Oxygen diffusion capacity was similarly raised in legs (P<0.05). Mitochondrial protein content remained unchanged in legs (P>0.05). Thus, BFR-interval training enhances oxygen utilization by, and lowers lactate release from, submaximally-exercising muscles of recreationally-trained men mainly by increasing leg convective oxygen transport.

Therapeutic Role of Dietary Nitrates on Cardiorespiratory Function in Cancer Survivors

IntroductionThe adverse physiological consequences of anticancer therapy include direct injury to the cardiovascular‐skeletal muscle axis. As such, cancer patients are at an increased risk of both cancer therapy‐related and age‐related pathological outcomes, including primary cardiovascular disease, exercise intolerance, and cancer‐related fatigue. To date, however, therapeutic strategies that mitigate these negative effects within the human body have yet to be established. Previous work has demonstrated that dietary nitrate (NO3−) supplementation can improve cardiac, vascular, and cardiorespiratory exercise parameters, highlighting its potential therapeutic use in clinical populations. Therefore, we hypothesized that NO3− supplementation improves both cardiac performance and exercise capacity. We also investigated the effects of NO3− supplementation on estimates of components of the convective oxygen transport pathway to obtain insight into potential mechanisms of action.MethodsTo date, 5 cancer survivors (58.6 ± 11.3 years) with a history of anticancer therapy completed a randomized, double‐blind, crossover study with an acute, single‐dose administration of NO3− or placebo (PL) [140 mL]. Transthoracic echocardiographic measures at rest were made to obtain left ventricular stroke volume. Patients performed a supine‐cycling steady‐state exercise test (30W) and a maximal‐effort cardiopulmonary exercise test, with measurements of arterial blood pressure, stroke volume, and cardiac output.ResultsThere was a statistically significant increase in plasma nitrite during the NO3− condition compared to PL (NO3− 1300 ± 963 μM vs. PL 111 ± 49 μM, respectively; P = 0.02). Additionally, we observed a decrease in oxygen uptake (VO2) during steady‐state exercise with NO3− compared to PL (NO3− 8.2 ± 2.4 vs. PL 8.6 ± 2.5 ml/kg/min; P = 0.03), indicating an improved exercise efficiency. Resting and steady‐state arterial blood pressure, stroke volume, and cardiac output were not different between conditions. Furthermore, we did not observe any differences between conditions for VO2 peak (NO3− 22.87 ± 4.14 vs. PL 23.45 ± 4.4 ml/kg/min; P = 0.31) or total work done (NO3− 75.73 ± 29.9 vs. PL 75.82 ± 31.3 kJ; P = 0.48) during the maximal‐effort cardiopulmonary exercise test. Similarly, there was no difference is peak cardiac output, convective O2 transport, or the arterial‐venous O2 difference.ConclusionsA single‐dose of inorganic nitrate supplementation in cancer survivors with a history of anticancer therapy enhanced steady‐state exercise efficacy, but had no effect on exercise cardiac performance or peak exercise capacity.

No ergogenic effects of a 10-day combined heat and hypoxic acclimation on aerobic performance in normoxic thermoneutral or hot conditions.

Hypoxic acclimation enhances convective oxygen delivery to the muscles. Heat acclimation-elicited thermoregulatory benefits have been suggested not to be negated by adding daily exposure to hypoxia. Whether concomitant acclimation to both heat and hypoxia offers a synergistic enhancement of aerobic performance in thermoneutral or hot conditions remains unresolved. Eight young males ([Formula: see text]: 51.6 ± 4.6mLmin-1kg-1) underwent a 10-day normobaric hypoxic confinement (FiO2 = 0.14) interspersed with daily 90-min normoxic controlled hyperthermia (target rectal temperature: 38.5°C) exercise sessions. Prior to, and following the confinement, the participants conducted a 30-min steady-state exercise followed by incremental exercise to exhaustion on a cycle ergometer in thermoneutral normoxic (NOR), thermoneutral hypoxic (FiO2 = 0.14; HYP) and hot (35°C, 50% relative humidity; HE) conditions in a randomized and counterbalanced order. The steady-state exercise was performed at 40% NOR peak power output (Wpeak) to evaluate thermoregulatory function. Blood samples were obtained from an antecubital vein before, on days 1 and 10, and the first day post-acclimation. [Formula: see text] and ventilatory thresholds were not modified in any environment following acclimation. Wpeak increased by 6.3 ± 3.4% in NOR and 4.0 ± 4.9% in HE, respectively. The magnitude and gain of the forehead sweating response were augmented in HE post-acclimation. EPO increased from baseline (17.8 ± 7.0 mIUmL-1) by 10.7 ± 8.8mIUmL-1 on day 1 but returned to baseline levels by day 10 (15.7 ± 5.9 mIUmL-1). A 10-day combined heat and hypoxic acclimation conferred only minor benefits in aerobic performance and thermoregulation in thermoneutral or hot conditions. Thus, adoption of such a protocol does not seem warranted.