Measurement Of Oxygen Consumption Research Articles

Workload and spirometry associated with untethered swimming in horses

BackgroundSwimming has been used empirically for rehabilitation and conditioning of horses. However, due to challenges imposed by recording physiological parameters in water, the intensity of free swimming effort is unknown.ObjectivesMeasure the physiological workload associated with untethered swimming in horses.Five fit Arabian endurance horses were assessed while swimming in a 100 m-long indoor pool. Horses were equipped with a modified ergospirometry facemask to measure oxygen consumption (V̇O2) and ventilatory parameters (inspired/expired volumes, VI, VE; peak inspiratory/expiratory flows, PkVI, PkVE; respiratory frequency, Rf; minute ventilation, VE; inspiratory/expiratory durations and ratios, tI, tE, tI/ttot, tE/ttot); and an underwater electrocardiogram that recorded heart rate (HR). Postexercise venous blood lactate and ammonia concentrations were measured. Data are reported as median (interquartile ranges).ResultsHorses showed bradypnea (12 breaths/min (10–16)) for the first 30 s of swimming. V̇O2 during swimming was 43.2 ml/(kg.min) (36.0–56.6). Ventilatory parameters were: VI = 16.7 L (15.3–21.8), VE = 14.7 L (12.4–18.9), PkVI = 47.8 L/s (45.8–56.5), PkVE = 55.8 L/s (38.3–72.5), Rf = 31.4 breaths/min (20.0–33.8), VE = 522.9 L/min (414.7–580.0), tI = 0.5 s (0.5–0.6), tE = 1.2 s (1.1–1.6), tI/ttot = 0.3 (0.2–0.4), tE/ttot = 0.7 (0.6–0.8). Expiratory flow tracings showed marked oscillations that coincided with a vibrating expiratory sound. HR was 178.0 bpm (148.5–182.0), lactate = 1.5 mmol/L (1.0–1.9) and ammonia = 41.0 µmol/L (36.5–43.5).ConclusionsFree (untethered) swimming represents a submaximal, primarily aerobic exercise in horses. The breathing pattern during swimming is unique, with a relatively longer apneic period at the beginning of the exercise and an inspiratory time less than half that of expiration.

SGLT2 inhibitors attenuate endothelial to mesenchymal transition and cardiac fibroblast activation

Beneficial effects of sodium glucose co-transporter 2 inhibitors (SGLT2is) in cardiovascular diseases have been extensively reported leading to the inclusion of these drugs in the treatment guidelines for heart failure. However, molecular actions especially on non-myocyte cells remain uncertain. We observed dose-dependent inhibitory effects of two SGLT2is, dapagliflozin (DAPA) and empagliflozin (EMPA), on inflammatory signaling in human umbilical vein endothelial cells. Proteomic analyses and subsequent enrichment analyses discovered profound effects of these SGLT2is on proteins involved in mitochondrial respiration and actin cytoskeleton. Validation in functional oxygen consumption measurements as well as tube formation and migration assays revealed strong impacts of DAPA. Considering that most influenced parameters played central roles in endothelial to mesenchymal transition (EndMT), we performed in vitro EndMT assays and identified substantial reduction of mesenchymal and fibrosis marker expression as well as changes in cellular morphology upon treatment with SGLT2is. In line, human cardiac fibroblasts exposed to DAPA showed less proliferation, reduced ATP production, and decelerated migration capacity while less extensive impacts were observed upon EMPA. Mechanistically, sodium proton exchanger 1 (NHE1) as well as sodium-myoinositol cotransporter (SMIT) and sodium-multivitamin cotransporter (SMVT) could be identified as relevant targets of SGLT2is in non-myocyte cardiovascular cells as validated by individual siRNA-knockdown experiments. In summary, we found comprehensive beneficial effects of SGLT2is on human endothelial cells and cardiac fibroblasts. The results of this study therefore support a distinct effect of selected SGLT2i on non-myocyte cardiovascular cells and grant further insights into potential molecular mode of action of these drugs.

O-287 Body composition analysis and metabolic monitoring before fertility treatment: hype or hope?

Abstract The effect of body mass index on both spontaneous and assisted fertility is well known: both lower and high indexes are correlated with negative outcome including live birth rate. Asides the dysmetabolic infertility that can develop by inflammation, insulin resistance and hyperandrogenemia, psychological and social factors deserve attention: a sexual self-image dysfunction is present in up to 20% of obese people with lower sexual desire and arousal. A positive note is that ART patients want to know about the impact of diet on fertility and ART success, asides the safety of the treatment and coping strategies, when asked about research priorities. Nevertheless, research in the field of preconception weight loss in the case of obesity in non-conclusive. The difference may lay in the strategy followed: lifestyle interventions may differ in approach, new weight-losing drugs might be involved or avoided, and targets and endpoints differ between studies. A first statement is to be made: body weight is a parameter of the past. In the world of nutrition, BMI is used to describe populations but fails to give accurate information about a single person. Body composition is more refined and can be used in follow-up. Asides dual energy X-ray absorptiometry (DXA), Bio Electrical Impedance Vector Analysis (BIVA) is used to endotype patients. Magnetic Resonance Imaging can, in a whole-body approach, provides very detailed information. In general, fat mass, fat free mass, phase angle (quantitative information) and fat infiltration of muscle (qualitative aspect) are considered ‘the kg of the future’. Associations between higher amounts of fat and poorer ART outcomes are published. As body composition is the result of food intake balanced to total energy expenditure (composed from basal energy expenditure, diet induced thermogenesis and physical activity level), the knowledge of these aspects can form a basis for a personalized approach. Techniques used in clinical practice relevant to this topic are food diary analysis by specialized dietitians (quantitative and qualitative analysis of food intake) and indirect calorimetry. This device will measure oxygen consumption and carbon dioxide production and calculate the basal metabolic rate in kcal/day. The concept of nutrition intake balanced to energy expenditure is validated in critically ill patients where it reduces mortality. It also showed benefit in a cancer population during active treatment. In a tertiary, university hospital in Brussels, Belgium, the forces of the fertility clinic and the nutrition department were combined: FerMet (Fertility-Metabolism). Patients seeking ART with a BMI <18;5 or higher than 30 are directed. Biophysical endotyping is performed by both metabolic screening, food intake analysis and baseline testing: body composition by BIVA and metabolic measurement by indirect calorimetry. A personalized intervention plan is developed in co-operation with the patient(s) by the dietitian and the supervising MD. Psychological reference or physical activity coaching is initiated if needed. Interim results: a total of 3793 men and woman in 3,5 years. In the population with a BMI below 20, which is only 6.4% of the entire group, body composition analysis reveals: only 9% are confirmed with alarmingly low body fat mass, such as seen in eating disorders. 23% has a fat mass percentage comparable to the general population and 66% represents what is known as ‘constitutional lean’. This might open opportunities to refine criteria to withhold ART based on body weight. In the overweight population, interventions can be tailored on individual metabolic rates and eating patterns, which is unique in the setting of ART. Whole Body MRi can be used in research settings. Benefits of this Biophysical Endotype based interventions to increase fertility outcomes need to be proven by further research.

Effects of substrate availability and mitochondrial disruption on oxidative metabolism and sperm motility in fertile dogs.

In several mammalian species, the measurement of mitochondrial oxygen consumption (MITOX) under different metabolic conditions has demonstrated a positive correlation with sperm motility and may be a sensitive indicator of mitochondrial health. In general, the maintenance of sperm motility and many key sperm functions and fertilizing events are heavily energy-dependent processes, and some species-specific substrate preferences exist. Although canine sperm have been known to undergo capacitation and maintain motility with supplementation of a wide range of energy substrates, the relationship between mitochondrial function, and the maintenance of oxidative metabolism and sperm motility remain unclear. The objective of this study was to explore the metabolic flexibility of canine sperm, and to investigate the relationship between mitochondrial function, and maintenance of motility under differing nutrient conditions. We explored substrate preferences and the bioenergetics underlying maintenance of canine sperm motility by monitoring mitochondrial oxidative function and sperm kinematics in the presence of mitochondrial effector drug treatments: FCCP, antimycin (ANTI), and oligomycin (OLIGO). We hypothesized that canine sperm possess the ability to use compensatory pathways and utilize diverse nutrient sources in the maintenance of motility. Oxygen consumption (change in pO2, oxygen partial pressure) and sperm kinematics (CASA) were measured concurrently (t0-t30) to assess the relationship between oxidative metabolism and maintenance of sperm motility in dogs. Four media were tested: containing glucose, lactate, and pyruvate (GLP), containing glucose (G), fructose (F), or lactate and pyruvate (LP). In the absence of pharmacological inhibition of the electron transport chain, energetic substrate had no effect on sperm kinematics in fertile dogs. Following mitochondrial disruption by ANTI and OLIGO, mitochondrial oxygen consumption was negatively correlated with several sperm motility parameters in GLP, G, F, and LP media. In every media, FCCP treatment quickly induced significantly higher oxygen consumption than in untreated sperm, and spare respiratory capacity, the maximal inducible oxidative metabolism, was high. With respiratory control ratios RCR >1 there was no indication of bioenergetic dysfunction in any media type, indicating that sperm mitochondria of fertile dogs have a high capacity for substrate oxidation and ATP turnover regardless of substrate. Our results suggest MITOX assessment is a valuable tool for assessing mitochondrial functionality, and that canine sperm employ flexible energy management systems which may be exploited to improve sperm handling and storage.

Estimating biofilm activity on biofilter elements in recirculating aquaculture systems (RAS) for rearing Atlantic salmon parr (Salmo salar) during operation with ozone and peracetic acid

Chemical disinfection in a recirculating aquaculture system (RAS) may affect biofilm-associated bacteria and the nitrification performance in the biofilter units. The biofilm response to chemical disinfectants in RAS remains unclear, but it can be understood using methods to quantify biofilm activity. Here, we compared the effects of two disinfection strategies, continuous ozone at 0.06 mg/L Cl2 equivalent (Ozone group) and peracetic acid (PAA) at 1 mg/L (PAA group) to control group without disinfectant, on biofilm activity on biofilter elements from nine identical experimental RAS with Atlantic salmon parr (Salmo salar) during a four-week trial. Biofilm activities on biofilter elements from the three groups were examined by measuring oxygen consumption rates (OCR) following sequential spiking with pure tap water, and tap water spiked with nitrite or ammonium, as well as oxygen release rate (kor) following hydrogen peroxide (H2O2) addition, to estimate metabolic activities of biofilm related to endogenous respiration and substrate turnover. The results show that the applied PAA dose increased the endogenous respiration activity of biofilm by 39–133%, stimulated the rate of biofilm enzymatic decomposition of H2O2 by 135%, and partially impaired the biofilm metabolism for nitrite oxidation (decrease by 36%), resulting in a significant nitrite accumulation (rise by 59%) in the cultured water, compared to control over experimental period. Ozone treatment caused an enhanced endogenous respiration activity of biofilm at the beginning of the experiment (increase by 45–74%), but dropped to control levels at the end of the experiment. The results indicate that chronic exposure to PAA can alter the metabolic state of biofilm, which can have consequences for biofilter functions, while chronic exposure to ozone improved water clarity without compromising the metabolic status of biofilm. The investigations provided insights into biofilm response to chemical disinfectant in RAS, which would benefit the optimization of an effective and safe use of disinfectants in RAS.

The use of thermal performance analysis to improve conservation management: The case of the invasive Red Sea swimming blue crab Portunus segnis

The latest report from the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) expresses concern over the global proliferation of non-native species (NIS) driven by increasing temperatures. In 2023, the invasive blue crab Portunus segnis in the Mediterranean experienced a significant range expansion due to warmer waters in northern and western regions. Recognizing thermal tolerance as crucial for conservation, this study, using the blue crab as a model, emphasized the importance of considering thermal metabolic performance in conservation efforts. In this study, we experimentally measured the metabolic performance of P. segnis at different temperatures (from 7 to 42°C) using an oxygen consumption measurement system. The thermal performance curve (TPC) of P. segnis rose from 0.016 ± 0.011 mgO2 h−1 gWW−1 (12°C) to 0.238 ± 0.011 mgO2 h−1 gWW−1 (34°C), and decreased beyond. Organisms succumbed at 7°C and 42°C. The TPC obtained was compared with 24 TPC models and the O’Neill regression was the best fitting model determining the minimum critical thresholds (CTmin) at 11.33°C and CTmax at 41.13°C. Using the TPC curve equation, we applied the curve to satellite Mediterranean temperature data for the year 2022 and for the future (RCP 4.5 and 8.5) to determine the current and future monthly distribution of favorable thermal habitats for P. segnis. Results anticipated the future expansion of the species along the Spanish, French, Italian, and Greek coasts of the Aegean Sea, providing maps to prioritize high-risk invasion areas. Additionally, in the areas where the species in currently present, results predicted a long-term persistence of the species. Understanding species' responses to temperature changes appears crucial for anticipating and addressing the impending expansion of invasive species, underscoring the urgency of nature conservation measures.

Changes in oxygen supply-demand balance during induction of general anesthesia: an exploratory study using remimazolam.

This study was performed to evaluate the changes in oxygen supply-demand balance during induction of general anesthesia using an indirect calorimeter capable of measuring oxygen consumption (VO2) and carbon dioxide production (VCO2). This study included patients scheduled for surgery in whom remimazolam was administered as a general anesthetic. VO2 and VCO2 were measured at different intervals: upon awakening (T1), 15min after tracheal intubation (T2), and 1h after T2 (T3). Oxygen delivery (DO2) was calculated simultaneously with these measurements. VO2 was ascertained using an indirect calorimeter and further calculated using vital signs, among other factors. DO2 was derived from cardiac output and arterial blood gas analysis performed with an arterial pressure-based cardiac output measurement system. VO2, VCO2, and DO2 decreased significantly from T1 to T2 and T3 [VO2/body surface area (BSA) (ml/min/m2): T1, 130 (122-146); T2, 107 (83-139); T3, 97 (93-121); p = 0.011], [VCO2/BSA (ml/min/m2): T1, 115 (105-129); T2, 90 (71-107); T3, 81 (69-101); p = 0.011], [DO2/BSA (ml/min/m2): T1, 467 (395-582); T2, 347 (286-392); T3, 382 (238-414); p = 0.0020]. Among the study subjects, a subset exhibited minimal reduction in VCO2. Although the respiratory frequency was titrated on the basis of end-tidal CO2 levels, there was no significant difference between the groups. General anesthetic induction with remimazolam decreased VO2, VCO2, and DO2.

Intraoperative Oxygen Consumption and Postoperative Immune Response in Colorectal Oncological Surgery: A Prospective, Monocentric Pilot Study.

Surgical resection is the key treatment for colorectal cancer, but the extent of surgical trauma has been implied as a key factor for the oncologic outcome. The immune stress response to surgical trauma generates a cascade of immunological events implying neutrophils' perioperative change generating NETosis, N killer decrease, and platelets' activation that may influence postoperative surgical outcome, tumor cell growth, and future oncogenesis. The present study aimed to investigate the correlation between intraoperative oxygen consumption (VO2) and the dynamic variation of neutrophils, lymphocytes, and platelets in the perioperative period to identify an intraoperative tool that could predict the postoperative immune response. Twenty-six colorectal oncological surgical patients were enrolled in an observational, prospective, monocentric study, over 18 months. Serum neutrophils, lymphocytes, and thrombocytes values were collected in the preoperative period and on the third postoperative day, oxygen consumption was measured and recorded every 15 min during surgery using indirect calorimetry. We compared oxygen consumption measurements registered 30 min after induction of anesthesia (VO2a) and the first value registered after abdominal wall closure (VO2b) to perioperative variation of absolute neutrophils (VNC), lymphocytes (VLC), and platelets (VPC) count. Our results proved a significant correlation between VO2 variation and neutrophils' perioperative dynamic assessed by VNC (correlation coefficient = 0.547, p < 0.01, 95% confidence interval (CI) =0.175, 0.783). We also noticed a correlation between VPC and VO2 (correlation coefficient = -0.603, p < 0.01, 95% CI = -0.815, -0.248). No correlation could be shown between VO2 and VLC variation (p = 0.39). In conclusion, intraoperative VO2 variation measured by indirect calorimetry correlates well with perioperative neutrophils and platelets count dynamic variations and can be used as an early prognosis marker of postoperative immune response and surgical outcome in colorectal oncological surgery.

Assessing the impact of imidacloprid, glyphosate, and their mixtures on multiple biomarkers in Corbicula largillierti

Pesticide mixtures are frequently utilized in agriculture, yet their cumulative effects on aquatic organisms remain poorly understood. Aquatic animals can be effective bioindicators and invasive bivalves, owing to their widespread distribution, provide an opportunity to assess these impacts. Glyphosate and imidacloprid, among the most prevalent pesticides globally, are frequently detected in freshwater systems in South America. This study aims to understand the cumulative effects of pesticide mixtures on aquatic organisms, using invasive Corbicula largillierti clams from a natural stream in northwestern Argentina. We conducted 48-hour exposure experiments using two concentrations of imidacloprid (20 and 200 μg L−1 a.i), two concentrations of glyphosate (0.3 and 3 mg L−1 a.i), and two combinations of these pesticides (both at low and high concentrations, respectively), simulating the direct contamination of both pesticides based on their agronomic recipe and observed values in Argentine aquatic environments. Clam metabolism was assessed through the examination of multiple oxidative stress parameters and measuring oxygen consumption rate as a proxy for standard metabolic rate (SMR). Our findings revealed that imidacloprid has a more pronounced effect compared to glyphosate. Imidacloprid significantly decreased clam SMR and cellular levels of reduced glutathione (GSH). However, when both pesticides were present, also cellular glycogen and thiobarbituric acid-reactive substances (TBARS) were affected. Proteins and glutathione S-Transferase (GST) activity were unaffected by either pesticide or their mixture at the assayed concentrations, highlighting the need to test several stress parameters to detect toxicological impacts. Our results indicated additive effects of imidacloprid and glyphosate across all measured parameters. The combination of multiple physiological and cytological biomarkers in invasive bivalves offers significant potential to enhance biomonitoring sensitivity and obtain insights into the origins and cellular mechanisms of chemical impacts. These studies can improve pollution regulatory policies and pesticide management.

Transport activity regulates mitochondrial bioenergetics and biogenesis in renal tubules.

Renal tubules are featured with copious mitochondria and robust transport activity. Mutations in mitochondrial genes cause congenital renal tubulopathies, and changes in transport activity affect mitochondrial morphology, suggesting mitochondrial function and transport activity are tightly coupled. Current methods of using bulk kidney tissues or cultured cells to study mitochondrial bioenergetics are limited. Here, we optimized an extracellular flux analysis (EFA) to study mitochondrial respiration and energy metabolism using microdissected mouse renal tubule segments. EFA detects mitochondrial respiration and glycolysis by measuring oxygen consumption and extracellular acidification rates, respectively. We show that both measurements positively correlate with sample sizes of a few centimeter-length renal tubules. The thick ascending limbs (TALs) and distal convoluted tubules (DCTs) critically utilize glucose/pyruvate as energy substrates, whereas proximal tubules (PTs) are significantly much less so. Acute inhibition of TALs' transport activity by ouabain treatment reduces basal and ATP-linked mitochondrial respiration. Chronic inhibition of transport activity by 2-week furosemide treatment or deletion of with-no-lysine kinase 4 (Wnk4) decreases maximal mitochondrial capacity. In addition, chronic inhibition downregulates mitochondrial DNA mass and mitochondrial length/density in TALs and DCTs. Conversely, gain-of-function Wnk4 mutation increases maximal mitochondrial capacity and mitochondrial length/density without increasing mitochondrial DNA mass. In conclusion, EFA is a sensitive and reliable method to investigate mitochondrial functions in isolated renal tubules. Transport activity tightly regulates mitochondrial bioenergetics and biogenesis to meet the energy demand in renal tubules. The system allows future investigation into whether and how mitochondria contribute to tubular remodeling adapted to changes in transport activity.

Low-Load and High-Load Resistance Exercise Completed to Volitional Fatigue Induce Increases in Postexercise Metabolic Responses With More Prolonged Responses With the Low-Load Protocol.

Grisebach, D, Bornath, DPD, McCarthy, SF, Jarosz, C, and Hazell, TJ. Low-load and high-load resistance exercise completed to volitional fatigue induce increases in post-exercise metabolic responses with more prolonged responses with the low-load protocol. J Strength Cond Res XX(X): 000-000, 2024-Comparisons of high-load with low-load resistance training (RT) exercise have demonstrated no differences in postexercise metabolism when volume is matched. This important limitation of matching or equating volume diminishes benefits of the low-load RT protocol. Therefore, the purpose of this study was to determine the effects of acute low-load high volume and high-load low volume RT protocols completed to volitional fatigue on postexercise metabolism. Eleven recreationally active resistance-trained male subjects (24 ± 2 years; BMI: 25.3 ± 1.5 kg·m-2) completed 3 experimental sessions: (a) no-exercise control (CTRL); (b) RT at 30% 1 repetition maximum (1RM; 30% 1RM); and (c) RT at 90% 1RM (90% 1RM) with oxygen consumption (V̇o2) measurements 2 hours postexercise. The RT sessions consisted of 3 sets of back squats, bench press, straight-leg deadlift, military press, and bent-over rows to volitional fatigue completed sequentially with 90 seconds of rest between sets and exercises. Changes were considered important if p < 0.100 with a ≥medium effect size. V̇o2 1 hour postexercise was elevated following 30% 1RM (25%; p = 0.003, d = 1.40) and 90% 1RM (14%; p = 0.010, d = 1.15) vs. CTRL and remained elevated 2 hours postexercise following 30% 1RM (16%; p = 0.010, d = 1.15) vs. CTRL. Total O2 consumed postexercise increased following 30% 1RM and 90% 1RM (∼17%; p < 0.044, d > 0.91) vs. CTRL. Fat oxidation was elevated 1 hour postexercise following 30% 1RM and 90% 1RM (∼155%; p < 0.001, d > 2.97) and remained elevated 2 hours postexercise following 30% 1RM compared with CTRL and 90% 1RM (∼69%; p < 0.030, d > 1.03). These data demonstrate beneficial changes to postexercise metabolism following high- and low-load RT sessions, with more prolonged effects following the low-load RT protocol completed to volitional fatigue.

Reaction Mechanisms of H2S Oxidation by Naphthoquinones.

1,4-naphthoquinones (NQs) catalytically oxidize H2S to per- and polysufides and sulfoxides, reduce oxygen to superoxide and hydrogen peroxide, and can form NQ-SH adducts through Michael addition. Here, we measured oxygen consumption and used sulfur-specific fluorophores, liquid chromatography tandem mass spectrometry (LC-MS/MS), and UV-Vis spectrometry to examine H2S oxidation by NQs with various substituent groups. In general, the order of H2S oxidization was DCNQ ~ juglone > 1,4-NQ > plumbagin >DMNQ ~ 2-MNQ > menadione, although this order varied somewhat depending on the experimental conditions. DMNQ does not form adducts with GSH or cysteine (Cys), yet it readily oxidizes H2S to polysulfides and sulfoxides. This suggests that H2S oxidation occurs at the carbonyl moiety and not at the quinoid 2 or 3 carbons, although the latter cannot be ruled out. We found little evidence from oxygen consumption studies or LC-MS/MS that NQs directly oxidize H2S2-4, and we propose that apparent reactions of NQs with inorganic polysulfides are due to H2S impurities in the polysulfides or an equilibrium between H2S and H2Sn. Collectively, NQ oxidation of H2S forms a variety of products that include hydropersulfides, hydropolysulfides, sulfenylpolysulfides, sulfite, and thiosulfate, and some of these reactions may proceed until an insoluble S8 colloid is formed.

TAKING A WALK ON THE HEART FAILURE SIDE: COMPARISON OF METABOLIC VARIABLES DURING WALKING AND MAXIMAL EXERTION

Abstract Background Although cardiopulmonary exercise testing (CPET) is the gold standard to assess exercise capacity, simpler tests (i.e. 6–minute walk test, 6MWT) are also commonly used. Aim of this study was to evaluate the relationship between cardiorespiratory parameters during CPET and 6MWT in a large, multicenter, heterogeneous population. Methods We included athletes, healthy subjects, and heart failure (HF) patients of different severity, including left ventricular assist device (LVAD) carriers, who underwent both CPET and 6MWT with oxygen consumption measurement. Results We enrolled 186 subjects (16 athletes, 40 healthy, 115 non–LVAD HF patients, and 15 LVAD carriers). CPET–peakV̇O2 was 41.0 [35.0–45.8], 26.2 [23.1–31.0], 12.8 [11.1–15.3], and 15.2 [13.6–15.6] ml/Kg/min in athletes, healthy, HF patients, and LVAD carriers, respectively (p&amp;lt;0.001). During 6MWT they used 63.5 [56.3–76.8], 72.0 [57.8– 81.0], 95.5 [80.3–109], and 95.0 [92.0–99.0] % of their peakV̇O2, respectively. None of the athletes, 1 healthy (2.5%), 30 HF patients (26.1%), and 1 LVAD carrier (6.7%), reached a 6MWT–V̇O2 higher than their CPET–peakV̇O2. Both 6MWT–V̇O2 and walked distance were significantly associated with CPET–peakV̇O2 in the whole population (R2=0.637 and R2=0.533, p=&amp;lt;0.001) but not in the sub–groups. This was confirmed after adjustment for groups. Conclusion The 6MWT can be a maximal effort especially in most severe HF patients and suggest that, in absence of prognostic studies related to 6MWT metabolic values, CPET should remain the first method of choice in the functional assessment of patients with HF as well as in sport medicine

Age-Related Vascular Mitochondrial Dysfunction Is Ameliorated by Time-Restricted Feeding Intervention

Endothelial dysfunction constitutes a hallmark of vascular aging that can have serious implications for disease risk. In addition, aging is associated with mitochondrial dysfunction, which can lead to increased oxidative stress and create associated damages. Time-restricted feeding (TRF) is a dietary intervention known to have many benefits on age-related disease risk. The objective of this study is to elucidate the effects of TRF upon endothelial mitochondrial function of aorta during aging. We hypothesized that TRF protects the aorta from age-related endothelial mitochondrial dysfunction. Adult C57BL/6 mice underwent TRF regimen, including six hours of ad libitum feeding daily. Young and age-matched control mice were fed ad libitum. After 12 months of TRF, wire myography was performed on aorta tissue as a measure of endothelial function. The aorta received pharmacological treatments to induce contraction, and dose-dependent dilation was quantified. For the first time, simultaneous measurement of reactive oxygen species (ROS) and oxygen consumption were completed in aorta tissue using Oroboros O2K Fluorespirometry. Dihydroethidium (DHE) fluorescent staining of ROS in aorta tissue was used to validate ROS measurements from O2K. Serum ketone body levels related to metabolic switching and relevant to mitochondrial biogenesis were determined. TRF improved endothelial-dependent dilation of aorta tissue, representing the intervention’s protection of endothelial function in aging. Aged TRF mice had greater oxygen consumption and less ROS in aorta tissue than age-matched control mice, indicating improved vascular mitochondrial function after TRF intervention. Aged TRF mice had elevated serum levels of ketone bodies involved in mitochondrial biogenesis. This supports the hypothesis that age-related changes in vascular mitochondrial health are alleviated by TRF. The knowledge gained from this study is relevant to understanding the mechanisms of age-related vascular dysfunction. Stephenson Cancer Center, National Institute of Aging R03 AG070479, American Heart Association. 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.

Quantifying in vivo Mitochondrial Effciency at Rest and during Exercise in Human Skeletal Muscle

Introduction: Mitochondrial effciency provides an additional mechanism to fine-tune oxidative phosphorylation rate to match ATP demand in skeletal muscle with far-reaching consequences on exercise tolerance. However, the direct measurement of both oxygen consumption (VO2) and ATP production from the same region of the contracting muscle in vivo remains a technical challenge. Purpose: Using an innovative approach combining noninvasive phosphorus and proton magnetic resonance spectroscopy (31P/1H-MRS), the present study aimed to characterize skeletal muscle ATP synthesis rate and muscle VO2 at rest and during a graded dynamic plantar flexion exercise to determine mitochondrial effciency in the gastrocnemius muscle. Method: We assessed mitochondrial effciency in the gastrocnemius muscles of 12 healthy adults (21± 1 yrs.). 31P and 1H magnetic resonance spectroscopy (MRS) was performed using a whole-body 3T MR system (Skyra, Siemens) at rest and during a series of constant workloads coupled to brief transient ischemia to quantify both oxidative ATP synthesis (ATPox) rate and myoglobin-derived oxygen consumption (Mb-derived VO2). The MRS data were acquired with a dual-tuned 31P/1H surface coil with linear polarization positioned over the gastrocnemius muscle. Results: As expected, the end-exercise PCr concentration decreased from 29 ± 2 mM of WRmax to 18 ± 1 mM with increasing workload. Likewise, the end-exercise Mb oxygenation level declined linearly with increasing workload. As the exercise workload increased, the ATPox synthesis rate increased linearly (r2 = 0.45), whereas there was no significant change in Mb-derived VO2. At rest, the estimated P/O ratio in the gastrocnemius muscle was 1.95 ± 0.68, whereas non-physiological values were obtained during exercise. Conclusion: During exercise, Mb-derived VO2 was likely limited by O2 availability with the methodology employed (30-sec occlusion, spectrum time resolution of 10 sec), which precluded the accurate quantification of mitochondrial effciency. However, mitochondrial effciency calculated at rest is in agreement with previously documented values ex vivo and thus provides an additional parameter to evaluate mitochondrial function in vivo. This work was funded in part by National Heart, Lung, and Blood Institute Grant R00HL125756. 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.

Selective breeding for high levels of voluntary exercise in mice does not reduce lifetime reproductive success or lifespan

The ways locomotor abilities may interact with life history traits are complicated and may involve shifts in resource allocation. For example, individuals that have large litters may have reduced energy available to support the organ systems required for high locomotor performance abilities. Alternatively, energy spent on excess physical activity might subtract from that available for somatic maintenance, and thus be negatively related to lifespan or to other fitness components that contribute to lifetime reproductive success (LRS). We studied lifetime reproductive successes, life span, and health span in mice from a long-term (&gt;100 generations) artificial selection experiment that includes 4 replicate High Runner (HR) lines bred for voluntary locomotor activity on wheels and 4 lines that serve as non-selected Controls (C). Since reaching selection limits at around generation 17-27 (depending on line and sex), the HR mice have been running ~3-fold farther on a daily basis as compared with C mice, for both sexes, which leads to substantially increased energy expenditure and food consumption. Importantly, when housed without wheels, HR mice are not only more active, but also consume more food than C mice. In the present study, we tested for differences in LRS between the HR and C lines. We are also comparing lifespan (median, maximum) and healthspan (e.g., by measurement of maximal oxygen consumption [VO2max] during forced exercise and maximal sprint speed. Twelve male-female pairs per line from generation 97 (born Oct. 2021) are being maintained until their end of life. In addition to total number of pups weaned per pair, we record components of LRS, such as age at first and last litter for the pairs, number of litters, and inter-birth intervals. Here, we present a subset of results through the first 2+ years of the experiment. Only two of 100 pairs never gave birth to any litters, and 89 of 100 pairs weaned at least one litter. The total number of litters born to pairs ranged from 0 to 12, and the number of litters from which at least one pup was weaned ranged from 0 to 11, with a mean of 3.96+0.73 (SE) for C lines and 3.43+0.65 for HR lines (P=0.61). The total number of pups weaned (our measure of LRS) ranged from 0 to 80, with a mean of 29.1+8.1 (SE) for C lines and 25.8+4.4 for HR lines (P=0.73). Thus, we found no evidence that Darwinian fitness has been reduced by artificial selection for high voluntary exercise. As of 1 Nov. 2023, approximately 17% of the breeders are still alive, and preliminary analyses do not indicate significant differences between the C and HR lines in median or maximum lifespan. Supported by U.S. National Science Foundation grant IOS-2038528. 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.

Hypoxia Exposure Fine-Tunes Mitochondrial Function in Primary Dermal Fibroblasts Derived from Loggerhead Sea Turtles

Sea turtles are constantly exposed to changes in oxygen tension derived from extended breath-hold diving, but the cellular-level response to such changes is not completely understood. Most studies in hypoxia-tolerant reptiles have focused on the freshwater turtle Trachemys scripta, which responds to anoxia by inducing metabolic rewiring and preserving mitochondrial integrity, facilitating effcient mitochondrial respiration during reoxygenation. Here, we derived primary dermal fibroblasts from loggerhead sea turtles and western fence lizards to study the bioenergetic cellular response to hypoxia exposure in diving and non-diving reptiles. Cells from both species stained positive for the fibroblast markers vimentin and PDGFRb and responded to hypoxia exposure (0.1% O2) by accumulating HIF-1α. We measured oxygen consumption rates (OCR) in intact cells using Seahorse technology. We found that basal, maximal, and spare respiratory capacity was lower in lizard than in loggerhead cells at 26oC under normoxic (room air) conditions (p &lt; 0.0001). Exposure to short (1h) and long-term hypoxia (24h) altered mitochondrial function in both species. Maximal and spare respiratory capacity were lower in loggerhead than in lizard cells (p &lt; 0.01) after 1h hypoxia followed by 1h reoxygenation. In contrast, basal and maximal respiratory capacity was higher in loggerhead compared to lizard cells after 24h hypoxia (p &lt; 0.04). Nonetheless, the overall OCR after 24h hypoxia in both species was lower than that observed after 1h hypoxia. Overall, there was a significant reduction in cellular respiration in both species from short-term to long-term hypoxia exposure. In lizard cells, basal OCR decreased by a factor of three while maximal OCR decreased by a factor of 4.5. In loggerhead cells, both the basal and maximal OCR decreased by a factor of two. Our results demonstrate species-specific regulation of cellular respiration after hypoxia exposure. Remarkably, loggerhead cells show a steady downregulation of cellular respiration in response to hypoxia exposure and faster recovery after extended hypoxia (24h) than lizard cells, aligning with the remarkable hypoxic tolerance exhibited by sea turtles, which can endure up to 7 hours of breath-holding underwater. Understanding the cellular mechanisms that drive hypoxic tolerance in diving animals can provide insights for treating human conditions characterized by hypoxia signaling. Ford Foundation. 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.

The Impact of Sex Hormones on Renal Mitochondrial Bioenergetics in Aging

Introduction. Aging is accompanied by changes in multiple factors, such as accumulation of mitochondrial dysfunction and the decline of sex hormone levels throughout life. Females are generally protected from renal diseases until menopause, potentially as a result of the presence of female sex hormones. Sex hormones govern a plethora of crucial renal processes, including metabolism and mitochondrial bioenergetics. However, there remains a gap in knowledge regarding the role of sex hormones in mitochondrial bioenergetics in renal aging. We hypothesized in this study that removal of sex hormones will exacerbate the aging-induced decline in renal mitochondrial function. Methods. Male and female Sprague Dawley (SD) rats were randomly divided into groups, and gonadectomy or sham surgery was performed before 4 wks of age. At 6 and 12 months of age kidneys were perfused to remove blood, then cortical tissues were immediately collected for mitochondrial isolations using differential centrifugation or snap-frozen/fixed for biochemical assays. Spectrofluorimetry was utilized to measure mitochondrial membrane potential (ΔΨm) and H2O2 production using TMRM and Amplex Red. Seahorse assay was done to measure oxygen consumption rate (OCR). OriginPro was used for statistical analysis (two-way ANOVA with Holm-Sidak post hoc). Results. Male OCR parameters (basal, ADP-linked, maximal and spare capacity) were lower than OCR observed in females at both 6 and 12 months of age (p&lt;0.05). Orchiectomy resulted in an increase in male OCR parameters at both ages (p&lt;0.05); ovariectomy did not affect renal cortical OCR (p&gt;0.05 for both ages). Of note, gonadectomy in males increased the OCR up to the female level (p&gt;0.05 for both ages). Cortical mitochondrial ΔΨm displayed similar values at 6 months across all groups. However, at 12 months we report lower ΔΨm in males vs female shams (p&lt;0.001). Of note, the male gonadectomy increased ΔΨm up to the level of female values, while ovariectomy had no effect (p=0.3). Female cortical H2O2 production was higher than in males (p&lt;0.001), whereas ovariectomy lowered H2O2 at both time points (p&lt;0.001), indicative of ΔΨm-independent ROS sources. Interestingly, the effect of testosterone on H2O2 production was dependent on age. At 6 months old, orchiectomy did not alter H2O2 production compared to shams, while at 12 months, orchiectomy led to higher H2O2 production (p&lt;0.001). Conclusions. Renal mitochondrial OCR was found to be independent of age in either sex at 6 and 12 months of age. Gonadectomy data allowed us to speculate that testosterone suppresses renal OCR, and the decreased membrane potential in males is likely driving the OCR changes. The observed ΔΨm-independent sources of H2O2 remain to be explored in future experiments. These data established the impact of sex hormones on mitochondrial bioenergetics and will help elucidate sex-specific targets that can mitigate the effects of aging on kidney function. Funding for this project came from 1U54HL169191. 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.

The Impact of Cardiorespiratory and Metabolic Parameters on Match Running Performance (MRP) in National-Level Football Players: A Multiple Regression Analysis

The aim of the study was to examine the association between cardiorespiratory and metabolic parameters and match running performance (MRP) in highly trained football players. The sample of participants consisted of 41 national-level football players (aged 23.20 ± 3.40 years, body height 182.00 ± 5.15 cm, and body mass 76.86 ± 6.06 kg) from the Serbian Super league. For the purposes of this research, the following measurements were applied. A maximal multistage progressive treadmill test, with a direct measurement of maximal oxygen consumption (VO2max) (using Fitmate MED, Cosmed, Rome, Italy) was conducted, alongside continuous heart rate monitoring. Capillary blood samples were taken from the hyperemic area using specific test strips, and, after sample collection, lactate concentration was immediately determined using a lactate analyzer. MRP variables were analyzed according to the BioIRC model of motion structure analysis, based on existing standards for profiling movement intensity. The results of multiple regression analysis indicated an association between cardiac parameters and total distance (R2 = 54.3%, p = 0.000), high-speed running (R2 = 46.4%, p = 0.000), and jogging (R2 = 33.6%, p = 0.004). Regression analysis revealed an association between cardiorespiratory parameters and total distance (R2 = 24.8%, p = 0.014), and high-speed running (R2 = 20%, p = 0.039). Meanwhile, no association was found between lactate concentration and running performance. The explanation for these regression analysis results is based on the observation that functional abilities represent significant potential for expressing movement performance, a crucial condition for success in football.

Changes in natural rubber mechanical behavior during oxidation: Relationship with oxygen consumption

This paper deals with the oxidation of rubber and more specifically with the possibility of setting up relationships between chemical degradation and its impact on mechanical properties for the lifetime prediction of polymers when the degradation process does not follow a single linear Arrhenian behavior. In this study, oxidation of unfilled natural rubber is first characterized at the molecular scale using oxygen consumption measurements for temperatures ranging from 115 °C to 21 °C. The results clearly show that oxidation does not follow a single linear Arrhenian behavior. Oxidation is then characterized at two other scales: the macromolecular scale using swelling measurements, and the macroscopic scale using tensile tests. Based on these findings, the relationship between the amount of oxygen consumed by the rubber and its crosslink density is first proposed within the temperature range of 115 °C to 85 °C. Finally, the relationships between the mechanical properties (Young modulus, elongation, and stress at break) and crosslink density of rubber are discussed.