O2 Extraction Research Articles

Combined effect of sprint interval training and post-exercise blood flow restriction on muscle deoxygenation responses during ramp incremental cycling.

This study investigated the effect of sprint-interval training combined with post-exercise blood flow restriction (i.e., SIT + BFR) on pulmonary gas exchange and microvascular deoxygenation responses during ramp incremental (RI) cycling. Nineteen healthy, untrained males (mean ± SD age: 24 ± 5years; height: 178 ± 6cm; body mass: 77.0 ± 10.7kg) were assigned to receive 4weeks of SIT or SIT + BFR. Before and after the intervention period, each participant completed a RI cycling test for determination of peak oxygen uptake ( ) and the gas exchange threshold (GET) with deoxygenated heme (Δdeoxy[heme]) and tissue oxygenation index (TOI) measured by near-infrared spectroscopy (NIRS) in vastus lateralis (VL) muscle. Relative increased by 7% following both interventions (P ≤ 0.03). SIT + BFR increased peak Δdeoxy[heme] when normalized relative to leg arterial occlusion (PRE: 57.3 ± 13.0 vs. POST: 62.0 ± 13.2%; P = 0.009) whereas there was no significant difference following SIT (PRE: 64.9 ± 14.3 vs. POST: 71.4 ± 11.7%; P = 0.17). Likewise, TOI nadir decreased at exhaustion following SIT + BFR (PRE: 56.9 ± 9.1 vs. POST: 51.4 ± 9.2%; P = 0.002) but not after SIT (PRE: 58.5 ± 7.1 vs. POST: 56.3 ± 8.2%; P = 0.29). The absolute cycling power at the GET increased following SIT + BFR (PRE: 108 ± 13 vs. POST: 125 ± 17 W, P = 0.001) but was not significantly different following SIT (PRE: 112 ± 7 VS. POST: 116 ± 11 W, P = 0.54). The addition of post-exercise BFR to SIT alters the mechanism underlying the enhancement in by increasing the peak rate of muscle fractional O2 extraction in previously untrained males.

Developing three-dimensional hydrophobic photocatalysts to enhance mass transfer for promoting hydrogen peroxide production

Photocatalytic oxygen reduction reaction (ORR) is a promising approach for hydrogen peroxide (H2O2) production to alternative conventional anthraquinone process. However, the slow O2 diffusion and low-efficiency water oxidation reaction (WOR, limitation of protons) pathways have restricted the H2O2 production efficiency of organic photocatalysts. Therefore, a promising strategy to develop photocatalysts with three-dimensional (3D) architectures possessing high O2 diffusion, high-efficiency WOR pathway, and quick H2O2 desorption is desirable. Herein, a hydrophobic two-dimensional porous organic polymer (2D-POP) based on tetraphenylethylene (TPE) was synthesized as the building block. 3D-POPs (TPE-2 and TPE-3) were subsequently developed through the Friedel-Crafts alkylation reaction to regulate the O2 adsorption and optical properties. The 3D architectures allow O2 to diffuse into the interlayers, leading to efficient extraction of O2 from air, thus an excellent H2O2 production rate of 2.57 mmol g−1 h−1has been achieved by TPE-2 in air and without sacrificial agents, which only decreases by 4% compared to that in O2 due to a suitable specific surface area, good photoelectric properties, and excellent mass transfer of O2, H+, and H2O2. Furthermore, the H2O2 production rate of TPE-2 reaches 2.67 mmol g−1 h−1 in a triphasic system in air, which is higher than that in a traditional diphasic system, and the concentration of H2O2 reaches 1.80 mmol L−1 h−1. Additionally, by adding external Fe2+ or Fe3+ to make the utmost of photogenerated H2O2 and trigger the in-situ Fenton reaction for the formation of ·OH, TPE-2 exhibits extraordinary photodegradation efficiency toward representative organic pollutants, reaching > 99% removal within 60 min for bisphenol A and 2,4-dichlorophenoxyacetic acid with high concentrations (200 ppm).

The role of the heart in the evolution of aerobic performance.

Aerobic metabolism underlies vital traits such as locomotion and thermogenesis, and aerobic capacity influences fitness in many animals. The heart is a key determinant of aerobic capacity, but the relative influence of cardiac output versus other steps in the O2 transport pathway remains contentious. In this Commentary, we consider this issue by examining the mechanistic basis for adaptive increases in aerobic capacity (thermogenic V̇O2,max; also called summit metabolism) in deer mice (Peromyscus maniculatus) native to high altitude. Thermogenic V̇O2,max is increased by acclimation to cold hypoxia (simulating high-altitude conditions), and high-altitude populations generally have greater V̇O2,max than their low-altitude counterparts. This plastic and evolved variation in V̇O2,max is associated with corresponding variation in maximal cardiac output, along with variation in other traits across the O2 pathway (e.g. arterial O2 saturation, blood haemoglobin content and O2 affinity, tissue O2 extraction, tissue oxidative capacity). By applying fundamental principles of gas exchange, we show that the relative influence of cardiac output on V̇O2,max depends on the O2 diffusing capacity of thermogenic tissues (skeletal muscles and brown adipose tissues). Functional interactions between cardiac output and blood haemoglobin content determine circulatory O2 delivery and thus affect V̇O2,max, particularly in high-altitude environments where erythropoiesis can increase haematocrit and blood viscosity. There may also be functional linkages between cardiac output and tissue O2 diffusion due to the role of blood flow in determining capillary haematocrit and red blood cell flux. Therefore, the functional interactions between cardiac output and other traits in the O2 pathway underlie the adaptive evolution of aerobic capacities.

Mechanisms of enhanced cardiorespiratory performance under hyperoxia differ with exposure duration in yellowtail kingfish.

Hyperoxia has been shown to expand the aerobic capacity of some fishes, although there have been very few studies examining the underlying mechanisms and how they vary across different exposure durations. Here, we investigated the cardiorespiratory function of yellowtail kingfish (Seriola lalandi) acutely (~20 h) and chronically (3-5 weeks) acclimated to hyperoxia (~200% air saturation). Our results show that the aerobic performance of kingfish is limited in normoxia and increases with environmental hyperoxia. The aerobic scope was elevated in both hyperoxia treatments driven by a ~33% increase in maximum O2 uptake (MO2max), although the mechanisms differed across treatments. Fish acutely transferred to hyperoxia primarily elevated tissue O2 extraction, while increased stroke volume-mediated maximum cardiac output was the main driving factor in chronically acclimated fish. Still, an improved O2 delivery to the heart in chronic hyperoxia was not the only explanatory factor as such. Here, maximum cardiac output only increased in chronic hyperoxia compared with normoxia when plastic ventricular growth occurred, as increased stroke volume was partly enabled by an ~8%-12% larger relative ventricular mass. Our findings suggest that hyperoxia may be used long term to boost cardiorespiratory function potentially rendering fish more resilient to metabolically challenging events and stages in their life cycle.

Dynamic Shift Towards Increased O2 Consumption and Reduced Lactate Uptake During Acute Volume Expansion in Sprague Dawley (SD) Rats

Rationale: In a recent study (PMID: 37575482), we established a method to assess alterations in O2 and substance metabolism in the kidneys in conscious free moving rat. This involved the repeated collection of renal arteriovenous blood and urine, alongside continuous measurements (24/7) of renal blood flow (RBF) and blood pressure (BP). Our previous studies demonstrated that in SD rats, there is an augmentation in RBF and GFR following chronic salt loading. Additionally, total renal O2 consumption (VO2) increases while there is a decrease in the net consumption of lactate with a tendency for its increased production. We hypothesize that these changes are not exclusive to the chronic phase of salt-loading but can also manifest during rapid increases of RBF and GFR. The primary aim of this study was to establish an experimental model reflecting these dynamics. Methods: SD rat (male, 10 wk age fed 0.4 NaCl (LS) diet, n=8) were studied. The jugular vein and femoral vein and artery were catheterized together with the renal vein. FITC-inulin (2 mg/mL) dissolved in 2%BSA saline was infused at 1.0 mL/100 g body wt/h from jugular vein. RBF was measured with an ultrasonic flow probe (Transonic, Inc) on the left renal artery and BP was measured through an arterial catheter. Whole blood, collected from donor rats, was diluted by 20% with saline, and a 6 mL volume expansion was performed with this solution over 1 hour. Blood was collected from both the renal venous and arterial catheters and urine from a ureteral catheter before and after volume expansion. O2 content was measured by radiometer and plasma lactate measured with a high sensitivity L-lactate fluorescent assay kit (ab169557, abcam). The same experiment was performed without volume expansion (i.e., sham study). O2 and lactate delivery and consumption were calculated as follows: Delivery = arterial content (A) x RBF; Consumption = (A − renal venous content (RV)) x RBF; Extraction = (A-RV) / A. Results: BP increased from 101 ± 3 to 111 ± 4 mmHg (p<0.05), RBF increased from 5.4 ± 0.5 to 7.9 to 0.6 mL/min/g kidney weight (gkw) (p<0.05) by volume expansion. GFR increased from 0.94 ± 0.06 to 1.19 ± 0.08 mL/min/gkw (p<0.05). O2 delivery increased from 1.06 ± 0.09 to 1.61 ± 0.12 mL/min/gkw (p<0.05). O2 consumption (VO2) increased from 0.06 ± 0.01 to 0.08 ± 0.01 mL/min/gkw (p<0.05). The O2 extraction ratio remained unchanged. Both lactate consumption (0.94 ± 0.11 to 0.47 ± 0.11 mM/gkw, p<0.05) and extraction ratio (0.18 ± 0.01 to 0.11 ± 0.02, p<0.05) were reduced by volume expansion. Conclusion: The increase of O2 consumption and reduction of lactate consumption with acute volume expansion model appear to be similar to those that we observed when SD rats were subjected to a chronic step increase of salt intake (from 0.4 to 4.0% NaCl). In contrast, however, an increase in O2 extraction was not observed with acute volume expansion as was the case with a high salt diet in which our studies have indicated that a prolonged tubular reabsorptive workload leads to enhanced oxidative stress with an uncoupling of oxidative phosphorylation. R01 HL151587, AHA 23POST1008714. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

NADPH Oxidase 4 Knockout in Dahl Salt-Sensitive Rats Impacts Kidney O2 Consumption and UCP2 Responses to a High Salt Diet

Rationale: The effects of a high salt (HS) diet upon renal metabolism and O2 utilization have not been extensively studied and there is a significant gap in our understanding of the role of oxidative stress in the effciency of energy production and substrate metabolism. The present study compared the effects of a HS diet (4% NaCl) on changes in O2 consumption and transcriptomic profiles in Dahl salt-sensitive (SS) rats to SS rats with a global knockout of NADPH oxidase 4 (NOX4) gene (SS Nox4−/−). Methods: Male SS (n=9) and SS Nox4−/− (n=10) rats were fed a 0.4% NaCl (LS) diet. At 7-8 weeks of age, the rats were implanted with a renal artery ultrasonic flow probe (Transonic) together with a femoral arterial catheter and a renal venous catheter. Renal blood flow (RBF) and mean arterial pressure (MAP) were measured continuously (24/7) and arterial (A) and renal venous (Vr) blood was sampled intermittently when rats were fed the LS and on days 7, 14, and 21 after switching to the HS diet. A and Vr blood O2 content was immediately measured by radiometer. From separate groups of rats subjected to the same protocol, the renal cortical tissue (Cx) and outer medulla (OM) were removed for mRNAseq analysis (Novogene, Inc). Results: When switching to the HS diet, the average 24-hour MAP of SS rats rose from 122 ± 2 to 140 ± 2 on HS7 to 164 ± 5 mmHg by HS21. In contrast, MAP in SS Nox4−/− rats increased from 121 ± 2 at LS to 132 ± 1 at HS7 to 152 ± 3 mmHg at HS21 (p<0.05, compared to SS). RBF, normalized by changes of kidney weights obtained in another group of SS and SS Nox4−/− rats fed the same HS diet, SS rats exhibited a significant reduction of RBF over the 3 weeks of the HS diet averaging LS 7.2 ± 0.6, HS7 5.1 ± 0.5 and HS21 4.6 ± 0.7 mL/min/g kidney weight (gkw). This reduction of RBF was not observed in SS Nox4−/− rats (LS 6.8 ± 0.8, HS7 6.6 ± 0.6, HS21 6.0 ± 0.6 mL/min/gkw). The kidney O2 extraction ratio at LS tended to be lower in SS Nox4−/− (11.2 ± 1.7%) compared to SS (14.0 ± 1.1%) (p=0.10). When switched to the HS diet, O2 extraction was significantly reduced in the SS Nox4−/− rats reaching 8.3 ± 1.0% at HS21 (p<0.05), while it did not change significantly in SS (12.7 ± 1.4%) at HS21. Notably, as determined by RNAseq analysis, Ucp2 expression in cortical tissue was significantly greater in SS fed HS than in SS Nox4−/−rats at HS21 . A gene enrichment analysis of the mRNAseq cortical tissue data (GSEA-KEGG pathways) focused on metabolic pathways indicated that knockout of Nox4 resulted in reduced expression of linoleic acid, lysine, and histidine metabolism pathways at LS when compared to SS. Those differences were not observed after HS feeding. However, upregulation of oxidative phosphorylation pathway was observed at HS21 in SS Nox4−/− when compared to SS rats. In the OM, a greater expression of genes associated with fatty acid degradation and carbon metabolism was observed in SS Nox4−/− rats when fed LS which was observed also at HS21. Conclusion: The preliminary results of this study suggest that reduced extraction of O2 in the SS Nox4−/− rats compared to SS rats may be partially explained by the differential response of Ucp2 to salt. Further studies are needed to determine whether the effciency of ATP production is enhanced in SS Nox4−/− as consequence of reduction of reactive oxygen species (e.g., H2O2) and the related downstream pathways such as phosphorylation of mTORC1. R01 HL151587, AHA 23POST1008714. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

BENEFICIAL EFFECTS OF A COMBINED AEROBIC AND STRENGTH TRAINING PROGRAM IN PATIENTS WITH MOTOR NEURON DISEASE

INTRODUCTION & AIMS Motor Neuron Disease (MND) is a neurodegenerative disease characterised by the progressive degeneration and death of motor neurons, which leads to a reduction in muscle strength and physical function. Although “Exercise as Medicine” is accepted for many diseases, the role of exercise in individuals with MND is still debated. The aim of this study was to evaluate the effect of a combined, moderate-intensity, aerobic and strength training program on aerobic capacities, strength and physical function in individuals with MND. METHODS Fifteen individuals with MND were randomly assigned to either a training (3 times/week for 12 weeks; TRAIN, n=8) or a control (continued their usual standard of care; CTRL, n=7) group. The peak aerobic capacity (VO2peak) and the maximal capacity of oxygen extraction (via Near-Infrared Spectroscopy) were evaluated during an incremental test to exhaustion on a cycle ergometer. The strength of both the lower- and upper-limb muscles was evaluated with a 1-Repetition Maximum (1RM) test on the leg press, leg extension, biceps curl, and vertical chest press. Participants also performed the “Timed Up and Go” test (TUG) and the 6-min walking test (6MWT). RESULTS The adherence to training was 86 ± 6%, and the satisfaction with the exercise program was 9.6 out of 10. VO2peak did not change significantly in both groups, but the maximal capacity of O2 extraction improved significantly in TRAIN (from 44 ± 3 to 67 ± 4%). In TRAIN, the 1RM for the leg press and leg extension increased significantly by 47 ± 8% and 50 ± 13%, respectively, while this parameter did not change in CTRL. While the 6MWT increased by 5% in TRAIN and decreased by 3% in CTRL, the change was not significant. CONCLUSION These preliminary results support the beneficial role of a combined aerobic and strength training program in individuals with MND.

Contributors to Diminished Cardiorespiratory Fitness in Young Users of Electronic Cigarettes

Background: Cardiorespiratory fitness, an independent marker of cardiovascular health, represents the ability of respiratory, cardiovascular, and muscular systems to effciently deliver and utilize oxygen (O2) during exercise. Recently, reduced cardiorespiratory fitness was identified in young and healthy, regular users of electronic (e-) cigarettes; however, its limiting factors are not established. Thus, the purpose of this study was to investigate the contributors to impaired cardiorespiratory fitness in young regular users of e-cigarettes. Methods: An evaluation of hemodynamics, chronotropic response, and oxygen utilization during exercise was completed in nineteen regular users of e-cigarettes (EU, age: 23±3 yr; e-cigarette usage 4±2 yr.) and sixteen demographically matched non-users (NU, age: 23±3 yr.). Hemodynamics were accessed via a non-invasive signal morphology impedance cardiography device, while chronotropic responses were measured as changes in peak heart rate (HR). Oxygen extraction ratio (difference in arterial and venous O2 content) at baseline and peak exercise was also recorded. Fold changes from rest to peak exercise were assessed to provide insight into potential factors that limit cardiorespiratory fitness. Results: At peak exercise, users of e-cigarettes exhibited significantly higher chronotropic incompetence ( p=0.033) and lower ( p=0.047) peak HR than non-users, with no differences in other hemodynamic assessments. Significantly ( p=0.025) lower skeletal muscle O2 extraction (EU=51±11 vs. NU=61±10%) was also observed in users of e-cigarettes during peak exercise. Fold changes in chronotropic (HR; p=0.915) and hemodynamic (cardiac output; p=0.279) responses were similar between both groups, while significant ( p=0.048) differences in oxygen extraction ratio were identified between the users of e-cigarettes (0.5±0.3 fold change) and non-users (0.8±0.3 fold change). Conclusions: Results from our study demonstrate that young, regular users of e-cigarettes exhibit abnormal chronotropic responses and impaired skeletal muscle oxygen utilization during exercise when compared to non-users, suggesting reduced cardiovascular and muscle health. Overall, our findings contribute to the growing body of evidence that supports the negative effects of regular e-cigarette use on young individuals. Supported in part by a Rapid Response Project NIDA/FDA (PRM). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Local O2 concentrating boosts the electro-Fenton process for energy-efficient water remediation

The electro-Fenton process is a state-of-the-art water treatment technology used to remove organic contaminants. However, the low O2 utilization efficiency (OUE, <1%) and high energy consumption remain the biggest obstacles to practical application. Here, we propose a local O2 concentrating (LOC) approach to increase the OUE by over 11-fold compared to the conventional simple O2 diffusion route. Due to the well-designed molecular structure, the LOC approach enables direct extraction of O2 from the bulk solution to the reaction interface; this eliminates the need to pump O2/air to overcome the sluggish O2 mass transfer and results in high Faradaic efficiencies (~50%) even under natural air diffusion conditions. Long-term operation of a flow-through pilot device indicated that the LOC approach saved more than 65% of the electric energy normally consumed in treating actual industrial wastewater, demonstrating the great potential of this system-level design to boost the electro-Fenton process for energy-efficient water remediation.

Haemodynamic compensations for exercise tissue oxygenation in early stages of COPD: an integrated cardiorespiratory assessment study

BackgroundCardiovascular comorbidities are increasingly being recognised in early stages of chronic obstructive pulmonary disease (COPD) yet complete cardiorespiratory functional assessments of individuals with mild COPD or presenting with COPD risk...

The Impact of Diabetes on Haemodynamic and Cardiometabolic Responses in Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection (HFpEF) and diabetes mellitus (DM) commonly co-exist. However, it is unclear if DM modifies the haemodynamic and cardiometabolic phenotype in patients with HFpEF. We aimed to interrogate the haemodynamic and cardiometabolic effects of DM in HFpEF. We compared the haemodynamic and metabolic profiles of non-DM patients and patients with DM-HFpEF at rest and during exercise using right heart catheterisation and mixed venous blood gas analysis. Of 181 patients with HFpEF, 37 (20%) had DM. Patients with DM displayed a more adverse exercise haemodynamic response vs HFpEF alone (mean pulmonary arterial pressure: 47 mmHg [interquartile range {IQR} 42-55] vs 42 [38-47], p<0.001; workload indexed pulmonary capillary wedge pressure indexed: 0.80 mmHg/W [0.44-1.23] vs 0.57 [0.43-1.01], p=0.047). HFpEF-DM patients had a lower mixed venous oxygen saturation at rest (70% [IQR 66-73] vs 72 [69-75], p=0.003) and were unable to enhance O2 extraction to the same extent (Δ-28% [-33 to -15] vs -29 [-36 to -21], p=0.029), this occurred at a 22% lower median workload. Resting mixed venous lactate levels were higher in those with DM (1.5 mmol/L [IQR 1.1-1.9] vs 1 [0.9-1.3], p<0.001), and during exercise indexed to workload (0.09 mmol/L/W [0.06-0.13] vs 0.08 [0.05-0.11], p=0.018). Concurrent diabetes and HFpEF was associated with greater metabolic responses at rest, with enhanced wedge driven pulmonary hypertension and relative lactataemia during exercise without appropriate augmentation of oxygen consumption.

Effects of concentric and eccentric cycling training on muscular hemodynamic and erythrocyte rheological responses to exercise in sedentary males

AbstractErythrocyte rheological properties contribute to the dynamic regulation of vascular resistance to flow shear force, facilitating blood delivery from the heart to peripheral tissues. Despite improved physical performance, the effects of eccentric cycling training (ECT) on erythrocyte rheological characteristics remain unclear. This study investigates the distinct effects of ECT and concentric cycling training (CCT) on muscular hemodynamic and erythrocyte rheological responses to exercise. Thirty‐nine sedentary healthy males were randomly assigned to either ECT (n = 13) or CCT (n = 13) at 45%–70% of the maximal workload for 30 min/day, 5 days/week for 6 weeks, or to a control group (n = 13) that did not receive any exercise intervention. A graded exercise test (GXT) was performed before and after the intervention. Muscular hemodynamic and erythrocyte rheological responses to the GXT were determined by near‐infrared spectroscopy and ektacytometry, respectively. Both ECT and CCT significantly enhanced perfusion (Δ[THb]VL) and O2 extraction (Δ[HHb]VL) in vastus lateralis during GXT. Before training, an acute GXT significantly reduced erythrocyte deformability and increased aggregability, whereas after 6 weeks of either ECT or CCT, the extent of erythrocyte rheological changes caused by GXT was diminished. Moreover, CCT elicited higher improvements in cardiac output (CO), VO2, and work‐rate at peak performance than ECT. In hierarchical regression, the change of maximal CO was the most influential factor affecting VO2max following CCT. In contrast, enhanced VO2max was significantly associated with Δ[HHb]VL and erythrocyte aggregability/deformability in ECT. Although CCT is superior to ECT for increasing aerobic capacity, either ECT or CCT effectively enhances aerobic efficiency by improving muscular hemodynamic and erythrocyte rheological responses to exercise.

Key Biophysical and Physiological Properties Impacting the Oxygenation Status of Breast Cancers During Thermo-radiotherapy.

Mild hyperthermia at 39-43°C for 30-60 min is applied locoregionally to improve the oxygenation status of recurrent breast cancers, thus enhancing the efficacy of radio-, chemo-, and immunotherapy. In this context, estimated (or even conflicting) data are often used in computational modelling of tumour oxygenation and simulation of O2 transport. In this chapter, we present information that may help to improve adjuvant thermotherapy delivered immediately prior to radiotherapy of recurrent breast cancers. Data are preferentially derived from clinical investigations; in some cases, measurements in experimental breast cancers are included.The biophysical properties presented for healthy, mostly postmenopausal, human breast (composite glandular-adipose-fibrous tissue) measured under normothermic (NT) conditions and in therapeutically heated breast cancers include tissue water content and tissue density. In general, averaged values of parameters reported for NT conditions are higher in breast cancers than in normal breast tissue, i.e., all ratios breast cancer/normal breast are >1. Mean values observed in breast cancers during mild hyperthermia (mHT) are consistently higher than those in NT tumours. Parameters determining convective transports in healthy breast tissue and breast cancer include blood flow rates, blood volume, exchanging water space, arterio-venous shunt flow, interstitial fluid flow rate, interstitial fluid pressure, microvascular permeability, interstitial hydraulic conductivity, and interstitial flow velocity. In general, averaged values of parameters measured under NT conditions are higher in breast cancers than in healthy breast. Except for interstitial fluid pressure, these values increase upon mHT treatment of cancers. Prime factors determining and describing the oxygenation status of the healthy breast, and in NT- versus mHT-treated breast cancers, include: oxygen (O2) delivery rates, O2- extractions, O2- consumption rates, subepidermal microvascular HbO2, tissue oxygen solubility, oxygen diffusion coefficients, mean O2 partial pressures pO2, hypoxic fractions HF<5mmHg, oxygen enhancement ratio, and mitochondrial ROS production. With the exception of the mean pO2, O2 extraction rate and tissue O2 saturation all parameters listed are distinctly higher in breast cancers under NT conditions compared to normal breast. Mild hyperthermia results in therapeutically relevant improvements of the oxygenation status of cancers and enhances mitochondrial ROS production, thus improving radiosensitivity. Note: The oxygenation status of the healthy (postmenopausal) breast is very similar to that of the normal human subcutis.

Reactive oxygen species mitigate perturbations in coronary microvascular tone in exercising swine with multiple risk factors

Abstract Background Multiple cardiovascular risk factors, such as diabetes mellitus (DM), chronic kidney disease (CKD) and dyslipidemia are known to induce inflammation and microvascular dysfunction contributing to impaired myocardial perfusion. We previously observed that a combination of DM, high fat diet (HFD) and CKD produced an increase in coronary microvascular tone in awake swine, resulting in perturbations in myocardial O2 balance. The increased microvascular tone was mediated by an impaired NO bioavailability and was accompanied by increased myocardial levels of reactive oxygen species (ROS) and increased circulating levels of endothelin (ET). Hypothesis: In the present study in swine, we tested the hypothesis that ROS scavenging and ET receptor blockade reduce coronary microvascular tone, improving myocardial O2 delivery and O2 balance in swine with DM+HFD+CKD. Methods DM (streptozotocin), HFD and CKD (renal artery embolization) were induced in 13 female swine (DM+HFD+CKD), while 11 healthy female swine on normal pig chow served as controls (Normal). After 6 months, the effects of ROS scavenging and ET receptor blockade on coronary microvascular tone were studied at rest and during graded treadmill exercise. Results 6 months of sustained hyperglycemia (18.1±1.0 in DM+HFD+CKD vs 8.5±0.6 mmol/l in Normal), hypercholesterolemia (12.3±2.0 vs 1.7±0.1 mmol/l) and renal dysfunction (plasma creatinine: 165±7 vs 119±3 µmol/l) were accompanied by systemic inflammation (TNF 52±5 vs 25±6 pg/ml), elevated ET plasma levels, (36±2 vs 29±2 pg/ml), and oxidative stress (myocardial PGF2a 12.9±0.8 vs 10.2±0.5 pg/mg protein, all P&amp;lt;0.05 by t-test). Surprisingly, in vivo ROS scavenging (TEMPOL+MPG) reduced myocardial O2 delivery (forcing an increased myocardial O2 extraction) in DM+HFD+CKD swine, indicative of a coronary microvascular constrictor response to ROS scavenging, implying a ROS-mediated vasodilator influence (Fig. A, B). In vitro experiments, using catalase in coronary small arteries, suggested a vasodilator role for hydrogen peroxide (H2O2) in DM+HFD+CKD but not in Normal swine. A switch from NO towards to H2O2 in the regulation of coronary microvascular tone was further supported by an increase in ceramide production (138±34 vs 45±4 nmol/ml, P&amp;lt;0.05) and increased activity of catalase in the myocardium (44±3 vs 31±4 nmol/min/mg, P&amp;lt;0.05) of DM+HFD+CKD vs Normal swine. Despite elevated ET plasma levels in DM+HFD+CKD swine, combined ETA/ETB receptor blockade with tezosentan did not affect myocardial O2 balance in either Normal or DM+HFD+CKD swine (Fig C, D). Conclusion In swine, 6 months exposure to multiple risk factors resulted in increased oxidative stress that paradoxically acted to mitigate perturbations in coronary microvascular tone via an H2O2-mediated coronary vasodilator influence. Despite an increase in circulating ET levels, we found no evidence for an increased ET-1 mediated coronary vasoconstrictor influence.

Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study.

While exercise impairments are central to symptoms and diagnosis of heart failure with preserved ejection fraction (HFpEF), prior studies of HFpEF biomarkers have mostly focused on resting phenotypes. We combined precise exercise phenotypes with cardiovascular proteomics to identify protein signatures of HFpEF exercise responses and new potential therapeutic targets. We analyzed 277 proteins (Olink) in 151 individuals (N=103 HFpEF, 48 controls; 62±11 years; 56% women) with cardiopulmonary exercise testing with invasive monitoring. Using ridge regression adjusted for age/sex, we defined proteomic signatures of 5 physiological variables involved in HFpEF: peak oxygen uptake, peak cardiac output, pulmonary capillary wedge pressure/cardiac output slope, peak pulmonary vascular resistance, and peak peripheral O2 extraction. Multiprotein signatures of each of the exercise phenotypes captured a significant proportion of variance in respective exercise phenotypes. Interrogating the importance (ridge coefficient magnitude) of specific proteins in each signature highlighted proteins with putative links to HFpEF pathophysiology (eg, inflammatory, profibrotic proteins),and novel proteins linked to distinct physiologies (eg, proteins involved in multiorgan [kidney, liver, muscle, adipose] health) were implicated in impaired O2 extraction. In a separate sample (N=522, 261 HF events), proteomic signatures of peak oxygen uptake and pulmonary capillary wedge pressure/cardiac output slope were associated with incident HFpEF (odds ratios, 0.67 [95% CI, 0.50-0.90] and 1.43 [95% CI, 1.11-1.85], respectively) with adjustment for clinical factors and B-type natriuretic peptides. The cardiovascular proteome is associated with precision exercise phenotypes in HFpEF, suggesting novel mechanistic targets and potential methods for risk stratification to prevent HFpEF early in its pathogenesis.

Association between Fractional Oxygen Extraction from Resting Quadriceps Muscle and Body Composition in Healthy Men.

This study aimed to associate body composition with fractional oxygen extraction at rest in healthy adult men. Fourteen healthy adults (26.93 ± 2.49 years) from Chile participated. Body composition was assessed with octopole bioimpedance, and resting muscle oxygenation was evaluated in the vastus lateralis quadriceps with near-infrared spectroscopy (NIRS) during a vascular occlusion test, analyzing the muscleVO2, resaturation velocity during reactive hyperemia via the muscle saturation index (%TSI), and the area above the curve of HHb (AACrep). It was observed that the total and segmented fat mass are associated with lower reoxygenation velocities during hyperemia (p = 0.008; β = 0.678: p = 0.002; β = 0.751), and that the total and segmented skeletal muscle mass are associated with higher reoxygenation velocities during hyperemia (p = 0.020; β = -0.614: p = 0.027; β = -0.587). It was also observed that the total and segmented fat mass were associated with a higher area above the curve of HHb (AACrep) during hyperemia (p = 0.007; β = 0.692: p = 0.037; β = 0.564), and that total and segmented skeletal muscle mass was associated with a lower area above the curve of HHb (AACrep) during hyperemia (p = 0.007; β = -0.703: p = 0.017; β = -0.632). We concluded that fat mass is associated with lower resaturation rates and lower resting fractional O2 extraction levels. In contrast, skeletal muscle mass is associated with higher resaturation rates and fractional O2 extraction during reactive hyperemia. The AACrep may be relevant in the evaluation of vascular adaptations to exercise and metabolic health.

Arterial Stiffness and Cardiorespiratory Fitness Impairment in the Community.

Background During exercise, a healthy arterial system facilitates increased blood flow and distributes it effectively to essential organs. Accordingly, we sought to understand how arterial stiffening might impair cardiorespiratory fitness in community-dwelling individuals. Methods and Results Arterial tonometry and maximum effort cardiopulmonary exercise testing were performed on Framingham Heart Study participants (N=2898, age 54±9 years, 53% women, body mass index 28.1±5.3 kg/m2). We related 5 arterial stiffness measures (carotid-femoral pulse wave velocity [CFPWV]: a measure of aortic wall stiffness; central pulse pressure, forward wave amplitude, characteristic impedance: measures of pressure pulsatility; and augmentation index: a measure of relative wave reflection) to multidimensional exercise responses using linear models adjusted for age, sex, resting heart rate, habitual physical activity, and clinical risk factors. Greater CFPWV, augmentation index, and characteristic impedance were associated with lower peak oxygen uptake (VO2; all P<0.0001). We observed consistency of associations of CFPWV with peak oxygen uptake across age, sex, and cardiovascular risk profile (interaction P>0.05). However, the CFPWV-peak oxygen uptake relation was attenuated in individuals with obesity (P=0.002 for obesity*CFPWV interaction). Higher CPFWV, augmentation index, and characteristic impedance were also related to cardiopulmonary exercise testing measures reflecting adverse O2 kinetics and lower stroke volume and peripheral O2 extraction but not to ventilatory efficiency, a prognostic measure of right ventricular-pulmonary vascular performance. Conclusions Our findings delineate relations of arterial stiffness and cardiorespiratory fitness in community-dwelling individuals. Future studies are warranted to evaluate whether the physiological measures implicated here may represent potential targets for improving cardiorespiratory fitness in the general population.

Beyond VO2: the complex cardiopulmonary exercise test.

Cardiopulmonary exercise test (CPET) is a valuable diagnostic tool with a specific application in heart failure (HF) thanks to the strong prognostic value of its parameters. The most important value provided by CPET is the peak oxygen uptake (peak VO2), the maximum rate of oxygen consumption attainable during physical exertion. According to the Fick principle, VO2 equals cardiac output (Qc) times the arteriovenous content difference [C(a-v)O2], where Ca is the arterial oxygen and Cv is the mixed venous oxygen content, respectively; therefore, VO2 can be reduced both by impaired O2 delivery (reduced Qc) or extraction (reduced arteriovenous O2 content). However, standard CPET is not capable of discriminating between these different impairments, leading to the need for 'complex' CPET technologies. Among non-invasive methods for Qc measurement during CPET, inert gas rebreathing and thoracic impedance cardiography are the most used techniques, both validated in healthy subjects and patients with HF, at rest and during exercise. On the other hand, the non-invasive assessment of peripheral muscle perfusion is possible with the application of near-infrared spectroscopy, capable of measuring tissue oxygenation. Measuring Qc allows, by having haemoglobin values available, to discriminate how much any VO2 deficit depends on the muscle, anaemia or heart.

Determinants of exercise performance in heart failure patients with extremely reduced cardiac output and left ventricular assist device.

The evaluation of exercise capacity and cardiac output (QC) is fundamental in the management of patients with advanced heart failure (AdHF). QC and peak oxygen uptake (VO2) have a pivotal role in the prognostic stratification and in the definition of therapeutic interventions, including medical therapies and devices, but also specific treatments such as heart transplantation and left ventricular assist device (LVAD) implantation. Due to the intertwined relationship between exercise capacity and daily activities, exercise intolerance dramatically has impact on the quality of life of patients. It is a multifactorial process that includes alterations in central and peripheral haemodynamic regulation, anaemia and iron deficiency, pulmonary congestion, pulmonary hypertension, and peripheral O2 extraction. This paper aims to review the pathophysiological background of exercise limitations in HF patients and to examine the complex physiology of exercise in LVAD recipients, analysing the interactions between the cardiopulmonary system, the musculoskeletal system, the autonomic nervous system, and the pump. We performed a literature review to highlight the current knowledge on this topic and possible interventions that can be implemented to increase exercise capacity in AdHF patients-including administration of levosimendan, rehabilitation, and the intriguing field of LVAD speed changes. The present paper confirms the role of CPET in the follow-up of this peculiar population and the impact of exercise capacity on the quality of life of AdHF patients.

Contributions of anemia to exercise intolerance in heart failure with preserved ejection fraction-An exercise stress echocardiographic study.

Anemia is common in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with exercise intolerance. However, there are limited data on how anemia contributes to reduced exercise capacity in patients with HFpEF. We aimed to characterize exercise capacity, cardiovascular and ventilatory reserve, and the oxygen (O2) pathway in anemic patients with HFpEF. A total of 238 patients with HFpEF and 248 dyspneic patients without HF underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. Patients with HFpEF were classified into two groups based on the presence of anemia (hemoglobin<13.0g/dL in men and<12.0g/dL in women). Anemic HFpEF patients (n=112) had worse nutritional status and renal function, lower iron levels, and greater left ventricular (LV) remodeling and plasma volume expansion than those without anemia (n=126). Exercise capacity, assessed by peak oxygen consumption, exercise intensity, and exercise duration, was lower in the anemic HFpEF group than in the other groups. Despite a similar cardiac output during exercise, anemic patients with HFpEF demonstrated limitations in arterial O2 delivery, lower arteriovenous O2 content difference, and ventilatory inefficiency (higher minute ventilation vs. carbon dioxide production slope) during peak exercise. Anemic HFpEF patients demonstrated unique pathophysiological features with greater LV remodeling and plasma volume expansion, limitations in arterial O2 delivery and peripheral O2 extraction, and ventilatory inefficiency, which may contribute to reduced exercise capacity. Further studies are needed to develop an optimal approach for treating anemia in patients with HFpEF.