O2 Difference Research Articles

Evidence that mitral and/or tricuspid regurgitation diminishes stroke volume increase during exercise

Abstract Background and Purpose The severity of heart failure can be evaluated by peak oxygen consumption (VO2). Cardiac output is one of the major essential factors to determine the VO2. Therefore, cardiac output increases linearly as the exercise intensity increases. However, in mitral regurgitation, effective stroke volume decreases due to some blood flowing back into the left atrium from the left ventricle. This reduction may compromise oxygen delivery to working muscles and diminish oxygen uptake. Peak VO2/HR is known to indicate the stroke volume at the peak exercise, but since c(A-V)O2 difference shows almost a similar change pattern during a ramp protocol, VO2/HR during the load is also reported to be an indicator of stroke volume (SV) at that work rate. However, there are no investigations that have examined the extent to which the increase in cardiac output during stress is affected by the severity of mitral regurgitation. Therefore, we investigated the influence of the degree of regurgitant volume in mitral regurgitation (MR) and tricuspid regurgitation (TR) affects the SV increasing response to exercise load. Additionally, we examined whether blunted SV increase influences on the peak VO2. Methods Among 525 patients who underwent cardiopulmonary exercise test (CPX) at our institution from January 2023 to October 2023, 518 patients (143 females, 375 males, mean age 65.2±15.0 years old) where precise analyses of CPX was possible. CPX was performed using breath-by-breath gas analysis, and an incremental load test (10watts/min) was administered until exhaustion. The rate of increase in VO2/HR per watt during an incremental loading (Δ(VO2/HR)/ΔWR) was used as an indicator of the degree of increase in SV. Typically, SV increases up to 60% of maximum load, around AT, after which it stops increasing and plateaus. Therefore, the slope of Δ(VO2/HR)/ΔWR was examined from the initiation of ramp loading to AT. The degree of reflux was evaluated by echocardiography and classified as none/trivial, mild and moderate/severe. The number of people in each group of None/trivial, mild, moderate/severe was, 392, 83, 30 for MR, and 416, 64, 24 for TR. Δ(VO2/HR)/ΔWR was evaluated for each degree of reflux, using ANOVA to determine whether there was a difference between groups. Results As shown in the Figure1, Δ(VO2/HR)/ΔWR decreased as the reflux flow rate increased for both MR and TR. Concurrently, peak VO2 also decreased in the moderate/severe group compared to the non/trivial-reflux group for both MR and TR (MR: 17.5±5.4 mL/min/kg vs. 14.9±3.5 mL/min/kg, TR: 17.2±5.3 mL/min/kg vs. 13.6±3.8 mL/min/kg). Conclusion The Δ(VO2/HR)/ΔWR obtained through CPX has been shown to be an index that can evaluate the severity of reflux. Additionally, it was also demonstrated that as regurgitation flow increased, true stroke volume decreases, which is correlated with a reduction in peak VO2.

Generation and Clearance of Superoxide Radicals at Buried Interfaces of Perovskites with Different Crystal Structures.

One of the most notorious issues with classic perovskite (MAPbI3) is its rapid degradation caused by generating superoxide radicals (O2 •-) on its surface under light and oxygen environments (light/O2). The differences in O2 •- generation rate and tolerance to O2 •- among perovskite with different structures are pending. For the first time it is validated through solid-electron paramagnetic resonance (EPR) that MAPbI3 and Cs0.175FA0.75MA0.075PbI3 (PVSK) crystals can generate O2 •- in an air atmosphere. The rapid degradation of perovskite buried interfaces caused by O2 •- dominates the nonexposed air aging process of SnO2-based perovskite film, and the degradation rate of MAPbI3 film is faster than that of PVSK film. The fullerene pyridine derivatives (C60OPD), which function as a buffer layer between SnO2 and PVSK to scavenge O2 •- and prevent degradation at the buried interface of the PVSK film, reduce the density of defect states, and accelerate the transmission of photogenerated electrons. The photoelectric conversion efficiency (PCE) of perovskite solar cells (PSCs) optimizes with C60OPD increased from 21.15% to 23.11% while significantly improving the stability in light/O2. This work reveals the hidden degradation of perovskite-buried interfaces caused by O2 •- and explores efficient ways for perovskite to resist O2 •-.

Six-year follow-up of a world record-breaking master marathon runner.

Endurance performance declines with advancing age. Of the three main physiological factors that determine endurance running performance [maximal oxygen consumption (V̇o2max), lactate threshold, and running economy (RE)], V̇o2max appears to be most affected by age. Although endurance performance declines with age, recently, endurance performance has rapidly improved in master athletes as the number of master athletes competing in endurance events has increased. Master athletes represent an intriguing model to study healthy aging. In this case study, we reassessed the physiological profile of a 76-yr-old distance runner who broke the marathon world record for men over 70 yr of age in 2018. This runner was tested a few months before breaking the world record and retested in 2024. Between 2018 and 2024, his marathon running velocity decreased significantly. Therefore, the purpose of this case study was to determine the physiological changes that explain his performance decline. RE remained similar to 2018, and while there was not a clear breakpoint in blood lactate, he still likely runs marathons at a high percentage (∼90%) of his V̇o2max. However, V̇o2max declined by 15.1%. HRmax declined by 3.2% and maximal O2 pulse declined by 12.4%, suggesting that maximal stroke volume and/or arteriovenous O2 difference decreased. Altogether, although this marathoner continues to compete at an elite level, his performance has declined since his record-breaking marathon due to a reduction in V̇o2max. This is likely caused by reductions in maximal stroke volume and/or arteriovenous O2 difference. We speculate that these changes reflect primarily age-related processes.NEW & NOTEWORTHY We performed 6-yr follow-up testing on a world record-breaking master marathon runner. We determined that his performance declined since his record-breaking marathon in 2018 primarily due to a reduction in V̇o2max. His max heart rate (HR) changed minimally, but his peak O2 pulse decreased, suggesting that his maximal stroke volume and/or arteriovenous O2 difference decreased. These changes likely reflect primarily age-related effects in the absence of an overt pathological disease process.

Variability in n-caprylate and n-caproate producing microbiomes in reactors with in-line product extraction.

Medium-chain carboxylates (MCCs) are used in various industrial applications. These chemicals are typically extracted from palm oil, which is deemed not sustainable. Recent research has focused on microbial chain elongation using reactors to produce MCCs, such as n-caproate (C6) and n-caprylate (C8), from organic substrates such as wastes. Even though the production of n-caproate is relatively well-characterized, bacteria and metabolic pathways that are responsible for n-caprylate production are not. Here, three 5 L reactors with continuous membrane-based liquid-liquid extraction (i.e., pertraction) were fed ethanol and acetate and operated for an operating period of 234 days with different operating conditions. Metagenomic and metaproteomic analyses were employed. n-Caprylate production rates and reactor microbiomes differed between reactors even when operated similarly due to differences in H2 and O2 between the reactors. The complete reverse β-oxidation (RBOX) pathway was present and expressed by several bacterial species in the Clostridia class. Several Oscillibacter spp., including Oscillibacter valericigenes, were positively correlated with n-caprylate production rates, while Clostridium kluyveri was positively correlated with n-caproate production. Pseudoclavibacter caeni, which is a strictly aerobic bacterium, was abundant across all the operating periods, regardless of n-caprylate production rates. This study provides insight into microbiota that are associated with n-caprylate production in open-culture reactors and provides ideas for further work.IMPORTANCEMicrobial chain elongation pathways in open-culture biotechnology systems can be utilized to convert organic waste and industrial side streams into valuable industrial chemicals. Here, we investigated the microbiota and metabolic pathways that produce medium-chain carboxylates (MCCs), including n-caproate (C6) and n-caprylate (C8), in reactors with in-line product extraction. Although the reactors in this study were operated similarly, different microbial communities dominated and were responsible for chain elongation. We found that different microbiota were responsible for n-caproate or n-caprylate production, and this can inform engineers on how to operate the systems better. We also observed which changes in operating conditions steered the production toward and away from n-caprylate, but more work is necessary to ascertain a mechanistic understanding that could be predictive. This study provides pertinent research questions for future work.

Effects of pacing strategy on metabolic responses to 2-min intense exercise in Thoroughbred horses

Evidence suggests that positive pacing strategy improves exercise performance and fatigue tolerance in athletic events lasting 1–5 min. This study investigated muscle metabolic responses to positive and negative pacing strategies in Thoroughbred horses. Eight Thoroughbred horses performed 2 min treadmill running using positive (1 min at 110% maximal O2 uptake [V̇O2max], followed by 1 min at 90% V̇O2max) and negative (1 min at 90% V̇O2max, followed by 1 min at 110% V̇O2max) pacing strategies. The arterial-mixed venous O2 difference did not significantly differ between the two strategies. Plasma lactate levels increased toward 2 min, with significantly higher concentrations during positive pacing than during negative pacing. Muscle glycogen level was significantly lower at 1 and 2 min of positive pacing than those of negative pacing. Metabolomic analysis showed that the sum of glycolytic intermediates increased during the first half of positive pacing and the second half of negative pacing. Regardless of pacing strategy, the sum of tricarboxylic acid cycle metabolites increased during the first half but remained unchanged thereafter. Our data suggest that positive pacing strategy is likely to activate glycolytic metabolism to a greater extent compared to negative pacing, even though the total workload is identical.

Lean body mass and the cardiorespiratory phenotype: An ethnic-specific relationship in Hans Chinese women and men.

Lean body mass (LBM) and the functional capacity of cardiovascular (CV) and respiratory systems constitute a female-specific relationship in European-American individuals. Whether this recent finding be extrapolated to the world's largest ethnic group, that is, Hans Chinese (HC, a population characterized by low LBM), is unknown. Healthy HC adults (n=144, 50% ♀) closely matched by sex, age and physical activity were included. Total and regional (leg, arm and trunk) LBM and body composition were measured via dual-energy X-ray absorptiometry. Cardiac structure, stiffness, central/peripheral haemodynamics and peak O2 consumption (VO2peak) were assessed via transthoracic echocardiography and pulmonary gas analyses at rest and during exercise up to peak effort. Regression analyses determined the sex-specific relationship of LBM with cardiac and aerobic phenotypes. Total and regional LBM were lower and body fat percentage higher in women compared with men (P<0.001). In both sexes, total LBM positively associated with left ventricular (LV) mass and peak volumes (r≥0.33, P≤0.005) and negatively with LV end-systolic and central arterial stiffness (r≥-0.34, P≤0.004). Total LBM strongly associated with VO2peak (r≥0.60, P<0.001) and peak cardiac output (r≥0.40, P<0.001) in women and men. Among regional LBM, leg LBM prominently associated with the arterio-venous O2 difference at peak exercise in both sexes (r≥0.43, P<0.001). Adjustment by adiposity or CV risk factors did not modify the results. LBM independently determines internal cardiac dimensions, ventricular mass, distensibility and the capacity to deliver and consume O2 in HC adults irrespective of sex.

Determinants of V̇+O2peak Changes After Aerobic Training in Coronary Heart Disease Patients.

This study aimed to highlight the ventilatory and circulatory determinants of changes in ˙VO2peak after exercise-based cardiac rehabilitation (ECR) in patients with coronary heart disease (CHD). Eighty-two CHD patients performed, before and after a 3-month ECR, a cardiopulmonary exercise testing (CPET) on a bike with gas exchanges measurements (˙VO2peak, minute ventilation, i. e., ˙VE), and cardiac output (Q˙c). The arteriovenous difference in O2 (C(a-v¯)O2) and the alveolar capillary gradient in O2 (PAi-aO2) were calculated using Fick's laws. Oxygen uptake efficiency slope (OUES) was calculated. A 5.0% cut off was applied for differentiating non- (NR: ˙VO2<0.0%), low (LR: 0.0≤ ∆˙VO2<5.0%), moderate (MR: 5.0≤∆˙VO2 < 10.0%), and high responders (HR: ∆˙VO2≥10.0%) to ECR. A total of 44% of patients were HR (n=36), 20% MR (n=16), 23% LR (n=19), and 13% NR (n=11). For HR, the ˙VO2peak increase (p<0.01) was associated with increases in ˙VE (+12.8±13.0 L/min, p<0.01), (+1.0±0.9 L/min, p<0.01), and C(a-v¯)O2 (+2.3±2.5 mLO2/100 mL, p<0.01). MR patients were characterized by+6.7±19.7 L/min increase in ˙VE (p=0.04) and+0.7±1.0 L/min of Q˙c (p<0.01). ECR induced decreases in ˙VE (p=0.04) and C(a-v¯)O2 (p<0.01) and a Q˙c increase in LR and NR patients (p<0.01). Peripheral and ventilatory responses more than central adaptations could be responsible for the ˙VO2peak change with ECR in CHD patients.

Selective Adsorption of Oxygen from Humid Air in a Metal-Organic Framework with Trigonal Pyramidal Copper(I) Sites.

High or enriched-purity O2 is used in numerous industries and is predominantly produced from the cryogenic distillation of air, an extremely capital- and energy-intensive process. There is significant interest in the development of new approaches for O2-selective air separations, including the use of metal-organic frameworks featuring coordinatively unsaturated metal sites that can selectively bind O2 over N2 via electron transfer. However, most of these materials exhibit appreciable and/or reversible O2 uptake only at low temperatures, and their open metal sites are also potential strong binding sites for the water present in air. Here, we study the framework CuI-MFU-4l (CuxZn5-xCl4-x(btdd)3; H2btdd = bis(1H-1,2,3-triazolo[4,5-b],[4',5'-i])dibenzo[1,4]dioxin), which binds O2 reversibly at ambient temperature. We develop an optimized synthesis for the material to access a high density of trigonal pyramidal CuI sites, and we show that this material reversibly captures O2 from air at 25 °C, even in the presence of water. When exposed to air up to 100% relative humidity, CuI-MFU-4l retains a constant O2 capacity over the course of repeated cycling under dynamic breakthrough conditions. While this material simultaneously adsorbs N2, differences in O2 and N2 desorption kinetics allow for the isolation of high-purity O2 (>99%) under relatively mild regeneration conditions. Spectroscopic, magnetic, and computational analyses reveal that O2 binds to the copper(I) sites to form copper(II)-superoxide moieties that exhibit temperature-dependent side-on and end-on binding modes. Overall, these results suggest that CuI-MFU-4l is a promising material for the separation of O2 from ambient air, even without dehumidification.

The Chinese cardiorespiratory and circulatory system at work in women and men: a case–control study

The physiology of prominent prognostic factors in the cardiorespiratory system remains unchartered in the world's largest ethnic group: Hans Chinese (HC). This study assessed and contrasted the fundamental variables in HC and European-American (EA) individuals. Healthy HC and EA adults (n=140, 43% ♀) closely matched by age, sex and physical activity were included. Body composition (DXA) and haematological variables (haemoglobin mass, blood volume (BV)) were measured at rest. Pulmonary O2 uptake (VO2) measurements along with cycle ergometry designed for accurate transthoracic echocardiography were implemented to assess cardiorespiratory structure/function up to peak effort. HC presented with higher body fat and lower lean body mass (LBM) percentage than EA irrespective of sex (P≤0.014). BV did not differ whereas blood haemoglobin concentration was lower in HC compared with EA, particularly in females (P=0.009). Myocardial diastolic and overall function at rest was enhanced in HC versus EA (P<0.001). During exercise, heart volumes and output per unit of body size did not differ between ethnicities, whereas larger heart volumes per unit of LBM were found in HC versus EA in females (P≤0.003). At high exercise intensities, VO2 (-16%) and the arteriovenous O2 difference (-28%) were markedly reduced in HC compared with EA in females (P≤0.024). In males, no physiological difference between HC and EA was observed during exercise. Notwithstanding lower LBM, HC are characterised by similar BV and cardiac capacity but reduced peak VO2 than EA in females, partly explained by low ethnic-specific blood O2 carrying capacity. Early Career Scheme (106210224, to D.M.) and Seed Fund (104006024, to D.M.).

Exercise gas exchange and echo-derived analysis in HFpEF based on patterns of oxygen peripheral utilization

Abstract Background Exercise limitation is a key signature of heart failure with preserved ejection fraction (HFpEF) syndrome evolution with studies highlighting a significant cardiac reserve limitation and others identifying a predominant limit in the peripheral VO2 kinetics and utilization. Aims To clarify the cardiopulmonary and hemodynamic response in HFpEF according to the high or low peripheral O2 utilization patterns during maximal exercise. Materials and Method 38 patients with a HFpEF diagnosis based on the ESC HFpEFF criteria underwent cardiopulmonary exercise test (CPET) combined with stress echocardiography. Patients were divided in two groups according to the median peak c(A-V) O2 difference (Group 1: &amp;lt; 11 mL/dL and Group 2: &amp;gt; 11 mL/dL). Cardiac output (CO) was calculated by echocardiography according to the formula LVOT velocity integral x LVOT area. Data were obtained after a familiarization CPET session. Results Group 1 and 2 presented similar rest demographic, left and right hemodynamic data (table). The relationship between CO and c (A-V) O2 in terms of VO2 isopleths at peak exercise were not related to any difference in CO (figure) Conclusions In HFpEF, an impairment in O2 utilization during exercise appears independent of the cardiac reserve response (similar peak CO increase) but rather peripheral mechanisms implicated in O2 diffusion/release seem to play a dominant role, emerging as selective therapeutic targets for improving functional capacity and symptoms.

Insulin resistance without coexisting hyperglycaemia is not independently associated with cardiorespiratory fitness or its components in women

Abstract Background Insulin resistance (IR) is a globally prevalent condition in which tissues’ response to insulin is diminished. Cardiorespiratory fitness (peak O2 uptake (VO2peak)) is determined by Fick’s equation (VO2 = cardiac output (CO) × arteriovenous O2 difference (Ca-vO2) = heart rate × stroke volume (SV) × Ca-vO2) and diffusion law (VO2 = diffusive O2 conductance (DO2) × constant k × venous O2 pressure (PvO2)). Several studies suggest an association between IR and decreased VO2peak, but the association has been questioned by analyses taking account of body size and composition, and potential mechanisms behind the association are unknown. Purpose To test a hypothesis that IR is not independently associated with VO2peak or its components. Methods Fifty of 144 women, who had participated in baseline experiments of three intervention studies, were included in this retrospective cross-sectional study; see Table 1 for subject characteristics. The inclusion criteria were age 18-40 years, body mass index 18.5-40 kg/m2, Caucasian origin, and available data on key measures. The exclusion criteria were diseases, medications, and other factors possibly affecting VO2peak. We measured haemoglobin, fasting glucose, and fasting insulin concentrations (blood), assessed IR (homeostasis model assessment (HOMA-IR)), and measured body size and composition (bioimpedance). The subjects performed an incremental cycling test to volitional fatigue; we measured ventilatory gas exchange (spiroergometry), arterial O2 saturation (oximetry), and SV and CO (impedance cardiography), and calculated Ca-vO2, DO2, and PvO2. We analysed VO2peak and its components as absolute (e.g. L/min) and ratiometrically scaled values (e.g. mL/min/kg), and when appropriate, also as allometrically scaled values (e.g. mL/min/kg^x, where 0 &amp;lt; x &amp;lt; 1) after identifying optimal variable-specific exponents. Results VO2peak scaled to body mass (BM) as well as SVpeak and COpeak scaled to body surface area (BSA) were inversely associated with the body size variables they were scaled to (all P &amp;lt; 0.013). Contrariwise, this was not the case when we optimally scaled VO2peak to fat-free mass (FFM), SVpeak to FFM^0.55, COpeak to FFM^0.50, and DO2peak to FFM (all 0.066 &amp;lt; P &amp;lt; 0.977). HOMA-IR was inversely associated with VO2peak scaled to BM but not in a multivariate analysis, whereas HOMA-IR was not associated with VO2peak scaled to FFM (Table 2); we made alike observations with SVpeak and COpeak (data not shown). Further, VO2peak scaled to BM as well as SVpeak and COpeak scaled to BSA were or tended to be up to 15 % higher in a group with HOMA-IR&amp;lt;3.0 than in a group with HOMA-IR≥3.0, while other peak exercise data did not differ between the groups (Table 1). Conclusion Body size and composition significantly affect conclusions drawn regarding VO2peak and its components. Taking this into account, IR without coexisting hyperglycaemia is not independently associated with VO2peak or its components in women.Table 1Table 2

Hypoxemia in patients with heart failure and preserved ejection fraction

Abstract Background Pulmonary abnormalities are common in patients with prevalent heart failure (HF). Arterial hypoxemia is considered rare in HF, but this has not been rigorously evaluated in patients with HF and preserved EF (HFpEF). Methods Results Patients with HFpEF (n=539) and no clinically-relevant lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxemia was defined by oxyhaeemoglobin saturation &amp;lt;94%. As compared to those without hypoxemia (n=403), patients with hypoxemia (n=136, 25%) were slightly older, heavier, and had higher NT-proBNP levels. They had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar-arterial O2 difference compared to those without hypoxemia. These differences were replicated in a sensitivity analysis where patients with any spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and capillary pressures were related to lower PaO2. The presence of exertional hypoxemia was associated with two-fold increased risk for death over 2.8 (IQR 0.7-5.5) years of follow up, (Adjusted:HR 2.00 (95%CI: 1.01−3.96), p=0.046). Conclusion One quarter of HFpEF patients displayed arterial desaturation during exercise. Patients with hypoxemia display more severely abnormal hemodynamics and increased mortality. Further study is required to better understand the mechanisms in patients with HFpEF.Hemodynamic changes at rest/exerciseRisk of death in HFpEF with hypoxemia

Cardiovascular responses of exercises performed within the extreme exercise domain.

Stroke volume (SV), heart rate (HR) and arterio-venous O2 difference (a-vO2diff) responses to heavy and severe-intensity exercise have been well documented; however, there is a lack of information on the SV, HR and a v-O2diff responses of work rates within extreme exercise domain. The aim of this study was, therefore, to focus on central and peripheral components of VO2 responses to exercises performed within the heavy, severe and extreme exercise domain. Eight well-trained male cyclists participated in this study. Maximal O2 consumption (VO2max) and corresponding work rate (P@VO2max) were determined by multisession constant work rate exercises. Cardiovascular responses to exercises were evaluated by nitrous-oxide rebreathing method with work rates from 40 % to 160 % of P@VO2max, VO2max corresponded to 324+/-39.4 W; however, maximal SV responses occurred at 205+/-54.3 W (p<0.01). Maximal cardiac output (Q), HR, and a vO2diff responses were revealed by the P@VO2max. VO2 response to exercise significantly decreased from severe-intense exercises to the first work rate of extreme exercise domain due to significant decreases in Q, SV, and HR responses (p<0.05), except a v-O2diff (p>0.05). Moreover, non-significant decreases in Q, SV, and a v-O2diff were evaluated as response to increase in work rate belonging to extreme work rates (p>0.05), except the HR (p<0.05). Work rates within the lower district of the extreme exercise domain have an important potential to improve peripheral component of VO2, while the P@VO2max seems the most appropriate intensity for aerobic endurance development as it maximizes the central component of VO2max.

PULM2: Combining Extracorporeal Lung and Kidney Support: Evaluation of Fibre Configurations on Gas Exchange Preservation for the Development of a Novel Highly Integrated Device (RenOx)

Background: Combined lung and kidney dysfunction are frequent in extracorporeal membrane oxygenation (ECMO) patients affecting up to 70% of them. Current treatment relies on the use of two separate circuits combining ECMO and renal replacement therapy, increasing infection risks and the use of artificial surfaces. Therefore, we aim to develop a novel artificial lung that integrates lung and kidney support in a single device combining oxygenation and hemodialysis fibers. Thus, we analyzed how many oxygenation fibers could be substituted by hemodialysis fibers while still maintaining 90% of the oxygenator’s gas exchange capacity and the effect fiber configuration has on oxygen (O2) and carbon dioxide (CO2) transfer. Methods: Fiber bundles were composed of oxygenation fiber mats (Oxyplus™ 90/200, 3M) stacked perpendicularly at a 90° angle and/or crossed at a 24° angle on top of each other. We manufactured bundles with all oxygenation fibers open and bundles with oxygenation fibers closed in a way that they could not contribute to gas exchange, simulating hemodialysis fibers. Bundles in perpendicular configuration had 100% of fibers open (Oxy100P), 50% of fibers closed (Oxy50P), or 25% of fibers closed (Oxy75P), Figure 1. Bundles in crossed configuration had all fibers open (Oxy100C) or 33% of fibers closed (Oxy67C). Bundles were tested for gas exchange performance following in-vitro blood tests according to ISO 7199:2016. Results: Our results show that bundles with 25% of oxygenation fibers closed in perpendicular configuration were able to still maintain 90% of the O2 exchange and 80% of the CO2 exchange capacity of our oxygenator. Bundles with 25% oxygenation fibers closed had no statistically significant difference in O2 or CO2 transfer compared to a fully open oxygenator with the same fiber configuration, Figure 2. Additionally, Oxy75P bundles were able to keep O2 delivery above 55 mL/LBlood flow and CO2 removal above 52 mL/LBlood flow up to 140 mL/min. Fiber configuration did not affect gas exchange for fully open bundles, however, configuration significantly influenced O2 and CO2 exchange for bundles with closed fiber layers. Closing fibers in perpendicular configuration resulted in a lower decrease in gas transfer. Below 140 mL/min, this was demonstrated by a similar decrease in O2 transfer of 20% when 50% of perpendicular fibers or 33% of crossed fibers were closed Conclusions: We analyzed the effect of replacing oxygenation fibers with hemodialysis fibers on gas exchange efficiency. Our results demonstrate that 25% of oxygenation fibers in a perpendicular configuration could be replaced by hemodialysis fibers while still maintaining 90% of the O2 exchange of our oxygenator. Moreover, this type of bundle kept O2 delivery above 55 mL/LBlood flow up to 140 mL/min. This shows that gas exchange can be preserved to a desirable extent when oxygenation fiber layers are replaced. This is a step towards combining lung and kidney support in a single device.Figure 1. Illustration of a device combining extracorporeal lung and kidney support. Oxygen flows through the lumen of oxygenation fibers and dialysate flows inside hemodialysis fibers. In this work, fiber bundles were manufactured with a perpendicular and/or crossed configuration having a varying number of oxygenation fiber layers closed, simulating hemodialysis fibers (open fibers in white and closed fibers in blue). Perpendicular bundles had 50% of fibers closed (Oxy50P), 25% of fibers closed (Oxy75P), or 100% of fibers open (Oxy100P), while crossed bundles had 33% of fibers closed (Oxy67C), or all fibers open (Oxy100C).Figure 2. Oxygen exchange performance mL/LBlood flow ± standard deviation from the mean (n = 10) for bundles with different fiber configurations. We found no statistically significant difference in mean oxygen exchange between Oxy75P and the fully open oxygenator Oxy100P (ANOVA p > 0.38).

Pulse Oximetry and Arterial Saturation Difference in Pediatric COVID-19 Patients: Retrospective Analysis by Race.

Pulse oximetry (Sp o2 ) may overestimate arterial oxygen saturation (Sa o2 ) in blood laboratory testing. This study aimed to assess Sp o2 -Sa o2 difference in relation to race (i.e., patient self-reporting as Black or White), occult hypoxemia, and length of stay (LOS) in pediatric patients with COVID-19. Single-center retrospective study in pediatric COVID-19 patients. We used multivariable linear regressions to examine the association between race and oximetry measurements and between occult hypoxemia and LOS. Oximetry bias was defined using Sp o2 and Sa o2 data according to approved comparisons. Occult hypoxemia was defined as Sp o2 greater than 92% and Sa o2 less than 88%. Quaternary pediatric hospital. Pediatric COVID-19 patients admitted to Texas Children's Hospital between May 2020 and December 2021. None. There were 2713 patients with complete physiological data in the analysis. Of the total, 61% were Black, and 39% were White. Oximetry bias was greater in Black compared with White patients ( p < 0.001), and this bias increased as the oxygen saturations decreased ( p < 0.001). Black and White patients had a 12% and 4% prevalence of occult hypoxemia, respectively ( p < 0.001). LOS was not associated with oximetry bias or occult hypoxemia once controlled for the level of support (intensive care, respiratory, circulatory). We found an oximetry bias in the measurement of Sp o2 with respect to Sa o2 in symptomatic hospitalized pediatric patients with the diagnosis of COVID-19. Furthermore, race is related to an increased oximetry bias. However, we did not find a relationship between oximetry bias and the LOS in the hospital in this cohort of patients.

Efficacy of Ranolazine to Improve Diastolic Performance in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis.

This article evaluates the efficacy of using ranolazine to improve diastolic performance and exercise capacity in heart failure with preserved ejection fraction. A comprehensive literature review found eight trials where there are no significant difference in peak O2 (p=0.09) and exercise duration (p=0.18) between ranolazine and placebo. The ranolazine group had significantly higher and better diastolic parameters compared to placebo, with a mean difference of 0.45 (95% CI [27.18-39.50]). There were no significant differences for haemodynamic parameters (blood pressure and heart rate) and electrocardiography (QT interval) between ranolazine and placebo. The review found that ranolazine has good wefficacy to improve diastolic performance among heart failure with preserved ejection fraction patients and it does not affect blood pressure, heart rate and rate of ventricular repolarisation (shortening of the QT interval).

Pulmonary ventilation and gas exchange during prolonged exercise in humans: Influence of dehydration, hyperthermia and sympathoadrenal activity.

What is the central question of the study? Ventilation increases during prolonged intense exercise, but the impact of dehydration and hyperthermia, with associated blunting of pulmonary circulation, and independent influences of dehydration, hyperthermia and sympathoadrenal discharge on ventilatory and pulmonary gas exchange responses remain unclear. What is the main finding and its importance? Dehydration and hyperthermia led to hyperventilation and compensatory adjustments in pulmonary CO2 and O2 exchange, such that CO2 output increased and O2 uptake remained unchanged despite the blunted circulation. Isolated hyperthermia and adrenaline infusion, but not isolated dehydration, increased ventilation to levels similar to combined dehydration and hyperthermia. Hyperthermia is the main stimulus increasing ventilation during prolonged intense exercise, partly via sympathoadrenal activation. The mechanisms driving hyperthermic hyperventilation during exercise are unclear. In a series of retrospective analyses, we evaluated the impact of combined versus isolated dehydration and hyperthermia and the effects of sympathoadrenal discharge on ventilation and pulmonary gas exchange during prolonged intense exercise. In the first study, endurance-trained males performed two submaximal cycling exercise trials in the heat. On day 1, participants cycled until volitional exhaustion (135± 11min) while experiencing progressive dehydration and hyperthermia. On day 2, participants maintained euhydration andcore temperature (Tc ) during a time-matched exercise (control). At rest and during the first 20min of exercise, pulmonary ventilation ( ), arterial blood gases, CO2 output and O2 uptake were similar in both trials. At 135±11min, however, was elevated with dehydration and hyperthermia, and this was accompanied by lower arterial partial pressure of CO2 , higher breathing frequency, arterial partial pressure of O2 , arteriovenous CO2 and O2 differences, and elevated CO2 output and unchanged O2 uptake despite a reduced pulmonary circulation. The increased was closely related to the rise in Tc and circulating catecholamines (R2 ≥0.818, P≤0.034). In three additional studies in different participants, hyperthermia independently increased to an extent similar to combined dehydration and hyperthermia, whereas prevention of hyperthermia in dehydrated individuals restored to control levels. Furthermore, adrenaline infusion during exercise elevated both Tc and . These findings indicate that: (1) adjustments in pulmonary gas exchange limit homeostatic disturbances in the face of a blunted pulmonary circulation; (2) hyperthermia is the main stimulus increasing ventilation during prolonged intense exercise; and (3) sympathoadrenal activation might partly mediate the hyperthermic hyperventilation.

Co-Firing Combustion Characteristics of Woodchips and Spent Mushroom Substrates in a 400 kWth Stoker-Type Boiler

The simultaneous firing characteristics of woodchips and spent mushroom substrates (SMS) were studied in a stoker-type industrial boiler. The type of spent substrate intended for combustion consisted of oyster mushrooms. SMS from mushroom farms generally have a high water content. Dryers are therefore used for combustion. The moisture content of SMS was reduced to achieve low moisture to combust sufficiently at about 20%. First, the basic characteristics of the boiler were confirmed by conducting a woodchip combustion test under various operating loads of 30, 50, 70, and 100%. Thereafter, a simultaneous combustion test of woodchips and SMS was performed. During the experiment, exhaust gas concentrations in the boiler combustion chamber were measured, such as the temperature of oxygen (O2), carbon monoxide (CO), and nitrogen oxides (NOx). In addition, industrial and basic analyses were performed on woodchips and SMS. The main differences in the fuel analysis results between woodchips and SMS were ash, nitrogen, sulfur content and net calorific value. According to the analysis, the nitrogen content of SMS was 2.6%, which was 8.7 times higher than that of woodchips, and the ash content was also 14.8%, which was 18.5 times that of woodchips. As a result of the combustion experiment, the woodchip experiment revealed that the values of O2 and CO decreased and the combustion chamber temperature increased as the amount of fuel increased. Due to higher combustion temperature, thermal NOx also increased. When comparing this combustion test with the co-firing test, there was no significant difference in O2, CO, and combustion chamber temperature. However, with regard to the NOx value, the results showed a sharp increase from 64 ppm to 135 ppm. Although the NOx value increased, SMS had enough heat to be burned as fuel. Therefore, the utility of various agricultural byproducts as fuel has prospects for achieving an effective approach to energy cost reduction.

Abstract 10041: Cardiopulmonary Performance Among Heart Failure Patients Before and After Left Ventricular Assist Device Implantation

Introduction: Continuous-flow left ventricular assist devices (CF-LVAD) improve survival and subjective assessments of health-related quality-of-life (HRqOL) when implanted into patients with advanced heart failure with reduced ejection fraction (HFrEF). However, functional capacity remains severely reduced. Hypothesis: LVAD flow during exercise contributes minimally to overall functional capacity. Exercise tolerance depends on intrinsic factors such as cardiac output (Qc) and arteriovenous oxygen difference (avo2 diff ). Methods: Ten patients (9 male, 60±10 years), underwent three invasive cardiopulmonary exercise tests on upright cycle ergometry. Visits were arranged 1) before (median, IQR: 0.3, 0.1-0.05 months) implantation, 2) after (4.2, 3.1-5.3 months) implantation with CF-LVAD speed held constant, and 3) with increases in pump speed during exercise (2.3, 1.9-3.0 months) after Visit 2. Submaximal functional capacity was measured by six-minute hall walk (6MHW). Fick Qc was measured via pulmonary artery catheter and gas exchange parameters determined by indirect calorimetry. Subjective assessments of HRqOL were obtained prior to and following implantation. Results: Following implantation, HRqOL and 6MHW improved. The avo2 diff and Qc predicted Watts achieved during exercise testing pre-implantation. The avo2diff, but not LVAD flow or Qc, predicted Watts achieved on multivariable analysis with both fixed and variable pumps speeds ( Table 1 ). Conclusions: Submaximal exercise performance and subjective HFrEF severity improved post implantation. The primary determinant of workload achieved during exercise testing, regardless of whether participants exercised at a fixed pump speed or with increases in pump speed, was the (A-V)O2 difference. LVAD flow contributes minimally to functional capacity.

Identification of Signaling and Functional Adaptations of Hematopoietic Stem/Progenitor Cells via Generation of a Low Oxygen Landscape

Hematopoietic stem and progenitor cells (HSC/HPC) reside in low O2 (1‐4%) bone marrow (BM) niches which provide critical signals for stem cell maintenance and function. Since the technology to directly compare broad signaling/functional differences of live HSC/HPC maintained in their native low O2 environment did not previously exist, historic studies have been performed in ambient air (~21% O2), utilizing whole (W) BM or fixed cells leading to a lack of mechanistic insight into endogenous signaling pathways/functional outcomes dependent on relevant microenvironmental O2. Using our novel technology to study live HSC/HPC in continuous low O2, we generated the first reference low O2 landscape of differential phenotypic/signaling/functional regulation in live HSC/HPC. Murine BM was harvested from long bones, enriched for SCA1+ cells, sorted for HSC/HPC (LSKCD150/LSK) fractions at continuous 3% O2 then split to remain in low O2 or be exposed to room air (60 minutes) with paired comparisons performed on the divided samples. Statistical analyses (t‐test or ANOVA) are based on multiple experiments (n&gt;3/experiment). All subsequent comparisons are between 3% O2 samples compared to room air exposed samples. Live cell analysis demonstrated enhanced phenotypic marker expression and frequency in low O2 of HSC (2‐fold), HPC (2‐fold), B‐cell‐ (B220) and erythroid‐lineage (Ter119) cells under low O2 (p&lt;0.05) relative to both historic data (utilizing WBM, fixed cells) and our room air data and identified masking of phenotypic difference in low O2 upon cell fixation. Transcriptional analyses of HPC detected 23,611 total genes; 1,239 were identified as differentially expressed (DEGs). HSC analyses detected 13,719 total genes with 135 identified DEGs (FDR&lt;0.05) in low O2. DAVID analysis of bulk mRNA sequencing identified differential pathway regulation of HPC (324 increased GO pathways, 230 decreased) and HSC (73 increased, 30 decreased) with significant enhancements of genes responsible for calcium regulation, transmembrane transport, and cell differentiation observed in low O2. Proteomic analysis of HPC detected 2,352 expressed proteins; 99 identified as differentially expressed (FDR&lt;0.05) and DAVID analysis highlighting enhancements in metabolism, cell signaling, and membrane regulation (p&lt;0.05) in low O2. Single cell sequencing of sorted HPC identified over 18,000 total genes in both air and low O2 with GSEA of significantly detected genes (p&lt;0.05) demonstrating differential regulation of cell cycle, metabolism, protein stabilization, enzyme binding/kinetics and calcium pathways in low O2. Functional analyses of HPC maintained at native low O2 revealed enhanced maintenance of HSC/HPC over 3‐4 re‐platings and altered fate decisions resulting in enhanced numbers of B‐cell‐, myeloid‐ (CD11b) and erythroid‐lineage (p&lt;0.05). These data provide novel insight into HSC/HPC endogenous signaling and function via generation of the first low O2 landscape and identified unique populations and differentially regulated pathways/gene signatures in low O2 vs. room air. Thus, highlighting the critical importance of native experimental conditions on data generation and interpretation in studies of HSC/HPC with potential broad implications for other stem cell populations.