Evaluation of calibrated and uncalibrated optical imaging approaches for relative cerebral oxygen metabolism measurements in awake mice.

Objective. The continuous delivery of oxygen is critical to sustain brain function, and therefore, measuring brain oxygen consumption can provide vital physiological insight. In this work, we examine the impact of calibration and cerebral blood flow (CBF) measurements on the computation of the relative changes in the cerebral metabolic rate of oxygen consumption (rCMRO2) from hemoglobin-sensitive intrinsic optical imaging data. Using these data, we calculate rCMRO2, and calibrate the model using an isometabolic stimulus.Approach. We used awake head-fixed rodents to obtain hemoglobin-sensitive optical imaging data to test different calibrated and uncalibrated rCMRO2models. Hypercapnia was used for calibration and whisker stimulation was used to test the impact of calibration.Main results. We found that typical uncalibrated models can provide reasonable estimates of rCMRO2with differences as small as 7%-9% compared to their calibrated models. However, calibrated models showed lower variability and less dependence on baseline hemoglobin concentrations. Lastly, we found that supplying the model with measurements of CBF significantly reduced error and variability in rCMRO2change calculations.Significance. The effect of calibration on rCMRO2calculations remains understudied, and we systematically evaluated different rCMRO2calculation scenarios that consider including different measurement combinations. This study provides a quantitative comparison of these scenarios to evaluate trade-offs that can be vital to the design of blood oxygenation sensitive imaging experiments for rCMRO2calculation.

When Studying Affective Responses to Exercise, the Definition of "Intensity" Must Reference Homeostatic Perturbations: A Retort to Vollaard et al.

In articles on the methodology of studies investigating affective and enjoyment responses to high-intensity interval training, we noted that, occasionally, exercise conditions described as involving "high" intensity exhibited heart rates that were only as high as, or even lower than, heart rates recorded during comparator conditions described as being of "moderate" intensity. Drs. Vollaard, Metcalfe, Kinghorn, Jung, and Little suggest instead that exercise intensity in high-intensity interval-training studies can be defined in terms of percentages of peak workload. Although we maintain that defining exercise intensity in terms of percentages of maximal heart rate is a suboptimal way to quantify the degree of homeostatic perturbations in response to exercise, we are unconvinced that definitions of intensity relying solely on workload are appropriate for studies investigating affective and enjoyment responses to exercise. The reason is that affect is theorized to have evolved to relay information about homeostatic perturbations to consciousness.

Effects of three weeks base training at moderate simulated altitude with or without hypoxic residence on exercise capacity and physiological adaptations in well-trained male runners.

Objectives: To test the hypothesis that 'live high-base train high-interval train low' (HiHiLo) altitude training, compared to 'live low-train high' (LoHi), yields greater benefits on performance and physiological adaptations. Methods: Sixteen young male middle-distance runners (age, 17.0 ± 1.5 y; body mass, 58.8 ± 4.9 kg; body height, 176.3 ± 4.3 cm; training years, 3-5 y; training distance per week, 30-60 km.wk-1) with a peak oxygen uptake averaging ~65 ml.min-1.kg-1 trained in a normobaric hypoxia chamber (simulated altitude of ~2,500 m, monitored by heart rate ~170 bpm; thrice weekly) for 3 weeks. During this period, the HiHiLo group (n = 8) stayed in normobaric hypoxia (at ~2,800 m; 10 h.day-1), while the LoHi group (n = 8) resided near sea level. Before and immediately after the intervention, peak oxygen uptake and exercise-induced arterial hypoxemia responses (incremental cycle test) as well as running performance and time-domain heart rate variability (5-km time trial) were assessed. Hematological variables were monitored at baseline and on days 1, 7, 14 and 21 during the intervention. Results: Peak oxygen uptake and running performance did not differ before and after the intervention in either group (all P > 0.05). Exercise-induced arterial hypoxemia responses, measured both at submaximal (240 W) and maximal loads during the incremental test, and log-transformed root mean square of successive R-R intervals during the 4-min post-run recovery period, did not change (all P > 0.05). Hematocrit, mean reticulocyte absolute count and reticulocyte percentage increased above baseline levels on day 21 of the intervention (all P < 0.001), irrespective of group. Conclusions: Well-trained runners undertaking base training at moderate simulated altitude for 3 weeks, with or without hypoxic residence, showed no performance improvement, also with unchanged time-domain heart rate variability and exercise-induced arterial hypoxemia responses.

Biomechanical, physiological and anthropometrical predictors of performance in recreational runners.

Background: The maximal running speed (VMAX) determined on a graded treadmill test is well-recognized as a running performance predictor. However, few studies have assessed the variables that predict VMAX in recreationally active runners. Methods: We used a mathematical procedure combining Fick's law and metabolic cost analysis to verify the relation between (1) VMAX versus anthropometric and physiological determinants of running performance and, (2) theoretical metabolic cost versus running biomechanical parameters. Linear multiple regression and bivariate correlation were applied. We aimed to verify the biomechanical, physiological, and anthropometrical determinants of VMAX in recreationally active runners. Fifteen recreationally active runners participated in this observational study. A Conconi and a stead-steady running test were applied using a heart rate monitor and a simple video camera to register the physiological and mechanical variables, respectively. Results: Statistical analysis revealed that the speed at the second ventilatory threshold, theoretical metabolic cost, and fat-mass percentage confidently estimated the individual running performance as follows: VMAX = 58.632 + (-0.183 * fat percentage) + (-0.507 * heart rate percentage at second ventilatory threshold) + (7.959 * theoretical metabolic cost) (R2 = 0.62, p = 0.011, RMSE = 1.50 km.h-1). Likewise, the theoretical metabolic cost was significantly explained (R2 = 0.91, p = 0.004, RMSE = 0.013 a.u.) by the running spatiotemporal and elastic-related parameters (contact and aerial times, stride length and frequency, and vertical oscillation) as follows: theoretical metabolic cost = 10.421 + (4.282 * contact time) + (-3.795 * aerial time) + (-2.422 * stride length) + (-1.711 * stride frequency) + (0.107 * vertical oscillation). Conclusion: Critical determinants of elastic mechanism, such as maximal vertical force and vertical and leg stiffness were unrelated to the metabolic economy. VMAX, a valuable marker of running performance, and its physiological and biomechanical determinants can be effectively evaluated using a heart rate monitor, treadmill, and a digital camera, which can be used in the design of training programs to recreationally active runners.

Chlorella Supplementation Reduces Blood Lactate Concentration and Increases O2 Pulse during Submaximal and Maximal Cycling in Young Healthy Adults.

Chlorella supplementation is reported to improve V˙O2max following extended supplementation periods (~3 weeks). However, there is little research on its impact over submaximal exercise intensities and following shorter supplementation regimens. This study aimed to investigate the efficacy of 6 g/day 2-day chlorella supplementation on exercise performance in healthy young adults. Twenty young healthy adults (Males = 16, Females = 4) (Age 22 ± 6 years, V˙O2max 42.7 ± 9.6 mL/(kg·min)) were recruited for this double-blinded, randomised cross-over study. Participants ingested 6 g/day of chlorella or a placebo for 2 days, with a one-week washout period between trials. Exercise testing consisted of a 20 min submaximal cycle at 40% of their work rate max (WRmax) (watts), followed by an incremental V˙O2max test. Lactate (mmol/L), heart rate (b/min), oxygen consumption (mL/(kg·min)), O2 pulse (mL/beat), respiratory exchange ratio (RER), and WRmax were compared across conditions. Following chlorella supplementation, blood lactate levels were significantly lower (p < 0.05) during submaximal exercise (3.05 ± 0.92 mmol/L vs. 2.67 ± 0.79 mmol/L) and following V˙O2max tests (12.79 ± 2.61 mmol/L vs. 11.56 ± 3.43 mmol/L). The O2 pulse was significantly higher (p < 0.05) following chlorella supplementation during submaximal (12.6 ± 3.5 mL/beat vs. 13.1 ± 3.5 mL/beat) and maximal exercise intensity (16.7 ± 4.6 mL/beat vs. 17.2 ± 4.5 mL/beat). No differences existed between conditions for oxygen consumption, RER, V˙O2max, or WRmax. A total of 2 days of 6 g/day chlorella supplementation appears to lower the blood lactate response and increase O2 pulse during both submaximal and maximal intensity exercise but did not lead to any improvements in V˙O2max.

Limb, sex, but not acute dietary capsaicin, modulate the near-infrared spectroscopy-vascular occlusion test estimate of muscle metabolism.

The downward slope during the near-infrared spectroscopy (NIRS)-vascular occlusion test (NIRS-VOT) is purported as a simplified estimate of metabolism. Whether or not the NIRS-VOT exhibits sex- or limb-specificity or may be acutely altered remains to be elucidated. Thus, we investigated if there is limb- or sex specificity in tissue desaturation rates (DeO2) during a NIRS-VOT, and if acute dietary capsaicin may alter this estimate of muscle metabolism. Young healthy men (n = 25, 21 ± 4 years) and women (n = 20, 20 ± 1 years) ingested either placebo or capsaicin, in a counterbalanced, single-blind, crossover design after which a simplified NIRS-VOT was conducted to determine the DeO2 (%/s), as an estimate of oxidative muscle metabolism, in both the forearm (flexors) and thigh (vastus lateralis). There was a significant limb effect with the quadriceps having a greater DeO2 than the forearm (-2.31 ± 1.34 vs. -1.78 ± 1.22%/s, p = 0.007, ηp 2 = 0.19). There was a significant effect of sex on DeO2 (p = 0.005, ηp 2 = 0.203) with men exhibiting a lesser DeO2 than women (-1.73 ± 1.03 vs. -2.36 ± 1.32%/s, respectively). This manifested in significant interactions of limb*capsaicin (p = 0.001, ηp 2 = 0.26) as well as limb*capsaicin*sex on DeO2 (p = 0.013, ηp 2 = 0.16) being observed. Capsaicin does not clearly alter O2-dependent muscle metabolism, but there was apparent limb and sex specificity, interacting with capsaicin in this NIRS-derived assessment.

Combined frequency domain near-infrared spectroscopy and diffuse correlation spectroscopy system for comprehensive metabolic monitoring of inspiratory muscles during loading.

Significance: Mechanical ventilation (MV) is a cornerstone technology in the intensive care unit as it assists with the delivery of oxygen in critically ill patients. The process of weaning patients from MV can be long and arduous and can lead to serious complications for many patients. Despite the known importance of inspiratory muscle function in the success of weaning, current clinical standards do not include direct monitoring of these muscles. Aim: The goal of this project was to develop and validate a combined frequency domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) system for the noninvasive characterization of inspiratory muscle response to a load. Approach: The system was fabricated by combining a custom digital FD-NIRS and DCS system. It was validated via liquid phantom titrations and a healthy volunteer study. The sternocleidomastoid (SCM), an accessory muscle of inspiration, was monitored during a short loading period in fourteen young, healthy volunteers. Volunteers performed two different respiratory exercises, a moderate load and a high load, which consisted of a one-minute baseline, a one-minute load, and a six-minute recovery period. Results: The system has low crosstalk between absorption, reduced scattering, and flow when tested in a set of liquid titrations. Faster dynamics were observed for changes in blood flow index (BFi), and metabolic rate of oxygen (MRO2) compared with hemoglobin + myoglobin (Hb+Mb) based parameters after the onset of loads in males. Additionally, larger percent changes in BFi, and MRO2 were observed compared with Hb+Mb parameters in both males and females. There were also sex differences in baseline values of oxygenated Hb+Mb, total Hb+Mb, and tissue saturation. Conclusions: The dynamic characteristics of Hb+Mb concentration and blood flow were distinct during loading of the SCM, suggesting that the combination of FD-NIRS and DCS may provide a more complete picture of inspiratory muscle dynamics.

Endurance training increases mitochondrial myoglobin and enhances its interaction with complex IV in rat plantaris muscle.

AIM: Endurance exercise training is known to increase mitochondrial respiration in skeletal muscle. However, the molecular mechanisms behind this are not fully understood. Myoglobin (Mb) is a member of the globin family, which is highly expressed in skeletal and cardiac muscles. We recently found that Mb localizes inside mitochondria in skeletal muscle and interacts with cytochrome c oxidase subunit IV (COXIV), a subunit of mitochondrial complex IV, which regulates respiration by augmenting complex IV activity. In the present study, we investigated the effect of endurance training on Mb-COXIV interaction within mitochondria in rat skeletal muscle. METHODS: Eight-week-old male Wistar rats were subjected to 6-week treadmill running training. Forty-eight hours after the last training session, the plantaris muscle was removed under anesthesia and used for biochemical analysis. RESULTS: The endurance training increased mitochondrial content in the skeletal muscle. It also augmented complex IV-dependent oxygen consumption and complex IV activity in isolated mitochondria from skeletal muscle. Furthermore, endurance training increased Mb expression at the whole muscle level. Importantly, mitochondrial Mb content and Mb-COXIV binding were increased by endurance training. CONCLUSION: These findings suggest that an increase in mitochondrial Mb and the concomitant enhancement of Mb interaction with COXIV may contribute to the endurance training-induced upregulation of mitochondrial respiration by augmenting complex IV activity.

Integrative Assessment of Cardiopulmonary Fitness Using Cardiopulmonary Exercise Test With Supine Bicycle Echocardiography in Patients Presenting Dyspnea.

BACKGROUND: Cardiopulmonary exercise test (CPET) with supine bicycle echocardiography (SBE) enables comprehensive physiologic assessment during exercise. We characterized cardiopulmonary fitness by integrating CPET-SBE parameters and evaluated its prognostic value in patients presenting with dyspnea. METHODS AND RESULTS: We retrospectively reviewed 473 consecutive patients who underwent CPET-SBE for dyspnea evaluation. A dimensionality reduction process was applied, transforming 24 clinical and CPET-SBE parameters into a 2-dimensional feature map, followed by patient clustering based on the data distribution. Clinical and exercise features were compared among the clusters in addition to the 5-year risk of clinical outcome (a composite of cardiovascular death and heart failure hospitalization). Maximum exercise effort (R >1) was achieved in 95% of cases. Through dimensionality reduction, 3 patient clusters were derived: Group 1 (n=157), 2 (n=104), and 3 (n=212). Median age and female proportion increased from Group 1 to 2, and 3, although resting echocardiography parameters showed no significant abnormalities among the groups. There was a worsening trend in the exercise response from Group 1 to 2 and 3, including left ventricular diastolic function, oxygen consumption, and ventilatory efficiency. During follow-up (median 6.0 [1.6-10.4] years), clinical outcome increased from Group 1 to 2 and 3 (5-year rate 3.7% versus 7.0% versus 13.0%, respectively; log-rank P=0.02), with higher risk in Group 2 (hazard ratio, 1.94 [95% CI, 0.52-7.22]) and Group 3 (3.92 [1.34-11.42]) compared with Group 1. CONCLUSIONS: Comprehensive evaluation using CPET-SBE can reveal distinct characteristics of cardiopulmonary fitness in patients presenting with dyspnea, potentially enhancing outcome prediction.

Reliability and criterion-related validity of the Cooper test in pre-adolescents and adolescents: A systematic review and meta-analysis.

The Cooper test (CT) is used to assess cardiorespiratory fitness (CRF) in pre-adolescents and adolescents, although it was originally developed to assess healthy adults. The aim of this study is to examine the available scientific evidence on the reliability and criterion validity of CT when administered to pre-adolescents and adolescents. Systematic searches were performed in three electronic databases (MEDLINE/PubMed, SPORTDiscuss and Scopus). To examine reliability and validity, four separate meta-analyses were implemented, finding high heterogeneity in studies with low methodological quality. There was a paucity of research regarding absolute reliability, while studies attempting to develop or cross-validate VO2max/VO2peak equations were almost non-existent. Information on the psychometric properties of CT in pre-adolescents under 12 years of age is scarce. The findings of this review cast doubt on the usefulness of CT both in identifying CRF and in determining the impact of strategies developed to improve CRF among pre-adolescents and adolescents.

Differential changes in blood flow and oxygen utilization in active muscles between voluntary exercise and electrical muscle stimulation in young adults.

The physiological effects on blood flow and oxygen utilization in active muscles during and after involuntary contraction triggered by electrical muscle stimulation (EMS) remain unclear, particularly compared with those elicited by voluntary (VOL) contractions. Therefore, we used diffuse correlation and near-infrared spectroscopy (DCS-NIRS) to compare changes in local muscle blood flow and oxygen consumption during and after these two types of muscle contractions in humans. Overall, 24 healthy young adults participated in the study, and data were successfully obtained from 17 of them. Intermittent (2-s contraction, 2-s relaxation) isometric ankle dorsiflexion with a target tension of 20% of maximal VOL contraction was performed by EMS or VOL for 2 min, followed by a 6-min recovery period. DCS-NIRS probes were placed on the tibialis anterior muscle, and relative changes in local tissue blood flow index (rBFI), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rMRO2) were continuously derived. EMS induced more significant increases in rOEF and rMRO2 than VOL exercise but a comparable increase in rBFI. After EMS, rBFI and rMRO2 decreased more slowly than after VOL and remained significantly higher until the end of the recovery period. We concluded that EMS augments oxygen consumption in contracting muscles by enhancing oxygen extraction while increasing oxygen delivery at a rate similar to the VOL exercise. Under the conditions examined in this study, EMS demonstrated a more pronounced and/or prolonged enhancement in local muscle perfusion and aerobic metabolism compared with VOL exercise in healthy participants.NEW & NOTEWORTHY This is the first study to visualize continuous changes in blood flow and oxygen utilization within contracted muscles during and after electrical muscle stimulation (EMS) using combined diffuse correlation and near-infrared spectroscopy. We found that initiating EMS increases blood flow at a rate comparable to that during voluntary (VOL) exercise but enhances oxygen extraction, resulting in higher oxygen consumption. Furthermore, EMS increased postexercise muscle perfusion and oxygen consumption compared with that after VOL exercise.

Mechanisms of Exercise Intolerance Across the Breast Cancer Continuum: A Pooled Analysis of Individual Patient Data.

PURPOSE: The purpose of this study is to evaluate the prevalence of abnormal cardiopulmonary responses to exercise and pathophysiological mechanism(s) underpinning exercise intolerance across the continuum of breast cancer (BC) care from diagnosis to metastatic disease. METHODS: Individual participant data from four randomized trials spanning the BC continuum ([1] prechemotherapy [n = 146], [2] immediately postchemotherapy [n = 48], [3] survivorship [n = 138], and [4] metastatic [n = 47]) were pooled and compared with women at high-risk of BC (BC risk; n = 64). Identical treadmill-based peak cardiopulmonary exercise testing protocols evaluated exercise intolerance (peak oxygen consumption; V̇O2peak) and other resting, submaximal, and peak cardiopulmonary responses. The prevalence of 12 abnormal exercise responses was evaluated. Graphical plots of exercise responses were used to identify oxygen delivery and/or uptake mechanisms contributing to exercise intolerance. Unsupervised, hierarchical cluster analysis was conducted to explore exercise response phenogroups. RESULTS: Mean V̇O2peak was 2.78 ml O2.kg-1·min-1 (95% confidence interval [CI], -3.94, -1.62 mL O2.kg-1·min-1; P < 0.001) lower in the pooled BC cohort (52 ± 11 yr) than BC risk (55 ± 10 yr). Compared with BC risk, the pooled BC cohort had a 2.5-fold increased risk of any abnormal cardiopulmonary response (odds ratio, 2.5; 95% confidence interval, 1.2, 5.3; P = 0.014). Distinct exercise responses in BC reflected impaired oxygen delivery and uptake relative to control, although considerable inter-individual heterogeneity within cohorts was observed. In unsupervised, hierarchical cluster analysis, six phenogroups were identified with marked differences in cardiopulmonary response patterns and unique clinical characteristics. CONCLUSIONS: Abnormal cardiopulmonary response to exercise is common in BC and is related to impairments in oxygen delivery and uptake. The identification of exercise response phenogroups could help improve cardiovascular risk stratification and guide investigation of targeted exercise interventions.

Discontinuous, biphasic, ontogenetic shifts in the metabolic allometry of aquatic animals?

Several investigations in recent years have reported patterns of discontinuous, biphasic, loglinear variation in the metabolic allometry of aquatic animals. These putative shifts in pattern of allometry have been attributed to changes in the primary site for gas exchange from cutaneous to branchial as animals undergo ontogenetic changes in size, shape, and surface area. Because of the important implications of the earlier research with regard to both physiology and evolution, I re-examined data that purportedly support claims of discontinuous, biphasic allometry in oxygen consumption versus body size of American eels (Anguilla rostrata) and spiny lobsters (Sagmariasus verreauxi). I used ANCOVA to fit three different statistical models to each set of logarithmic transformations and then assessed the fits by Akaike's Information Criterion. The observations for both species were described better by a single straight line fitted to the full distribution than by a biphasic model. Eels, lobsters, and other aquatic animals undergo changes in shape and surface area as they grow, but such changes are not necessarily accompanied by changes in the pattern of metabolic allometry.

Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction.

The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS-CoV-2 virus ("long COVID") is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age-/sex-matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p < 0.001), and lower oxidative capacity, measured using near infrared spectroscopy (τ: 38.7 (31.9, 45.6) vs. 24.6 (19.1, 30.1) s, p = 0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multisystem factors might contribute to impaired exercise tolerance in long COVID sufferers.

Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb-/- mice.

Myoglobin (Mb) plays an important role at rest and during exercise as a reservoir of oxygen and has been suggested to regulate NO• bioavailability under hypoxic/acidic conditions. However, its ultimate role during exercise is still a subject of debate. We aimed to study the effect of Mb deficiency on maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and exercise performance in myoglobin knockout mice (Mb-/- ) when compared to control mice (Mb+/+ ). Furthermore, we also studied NO• bioavailability, assessed as nitrite (NO2 - ) and nitrate (NO3 - ) in the heart, locomotory muscle and in plasma, at rest and during exercise at exhaustion both in Mb-/- and in Mb+/+ mice. The mice performed maximal running incremental exercise on a treadmill with whole-body gas exchange measurements. The Mb-/- mice had lower body mass, heart and hind limb muscle mass (P < 0.001). Mb-/- mice had significantly reduced maximal running performance (P < 0.001). V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ expressed in ml min-1 in Mb-/ - mice was 37% lower than in Mb+/+ mice (P < 0.001) and 13% lower when expressed in ml min-1  kg body mass-1 (P = 0.001). Additionally, Mb-/- mice had significantly lower plasma, heart and locomotory muscle NO2 - levels at rest. During exercise NO2 - increased significantly in the heart and locomotory muscles of Mb-/- and Mb+/+ mice, whereas no significant changes in NO2 - were found in plasma. Our study showed that, contrary to recent suggestions, Mb deficiency significantly impairs V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance in mice. KEY POINTS: Myoglobin knockout mice (Mb-/- ) possess lower maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and poorer maximal running performance than control mice (Mb+/+ ). Respiratory exchange ratio values at high running velocities in Mb-/- mice are higher than in control mice suggesting a shift in substrate utilization towards glucose metabolism in Mb-/- mice at the same running velocities. Lack of myoglobin lowers basal systemic and muscle NO• bioavailability, but does not affect exercise-induced NO2 - changes in plasma, heart and locomotory muscles. The present study demonstrates that myoglobin is of vital importance for V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance as well as explains why previous studies have failed to prove such a role of myoglobin when using the Mb-/- mouse model.

The Child Opportunity Index 2.0 and Disparities in Pediatric Cardiorespiratory Fitness.

OBJECTIVE: To evaluate the effect of neighborhood-level characteristics on cardiorespiratory fitness (CRF) via peak oxygen consumption (VO2peak) for healthy pediatric patients. STUDY DESIGN: The institutional cardiopulmonary exercise testing (CPET) database was analyzed retrospectively. All patients aged ≤ 18 years without a diagnosis of cardiac disease and with a maximal effort CPET were included. Patients were divided into three self-identified racial categories: White, Black, and Latinx. The Child Opportunity Index (COI) 2.0 was used to analyze social determinants of health. CRF was evaluated based on COI quintiles and race. Assessment of the effect of COI on racial disparities in CRF was performed using ANCOVA. RESULTS: A total of 1753 CPETs met inclusion criteria. The mean VO2peak was 42.1 ± 9.8 mL/kg/min. The VO2peak increased from 39.1 ± 9.6 mL/kg/min for patients in the very low opportunity cohort to 43.9 ± 9.4 mL/kg/min for patients in the very high opportunity cohort. White patients had higher percent predicted VO2peak compared with both Black and Latinx patients (P < .01 for both comparisons). The racial differences in CRF were no longer significant when adjusting for COI. CONCLUSION: In a large pediatric cohort, COI was associated with CRF. Racial disparities in CRF are reduced when accounting for modifiable risk factors.

A Higher Kick Frequency Swimming Training Program Optimizes Swim-to-Cycle Transition in Triathlon.

ABSTRACT: Ambrosini, L, Presta, V, Vitale, M, Menegatti, E, Guarnieri, A, Bianchi, V, De Munari, I, Condello, G, and Gobbi, G. A higher kick frequency swimming training program optimizes swim-to-cycle transition in triathlon. J Strength Cond Res 38(5): 976-984, 2024-The purpose of this study was to evaluate the effect of an 8-week swimming training program on biomechanical and physiological responses during a swim-to-cycle simulation. Fifteen triathletes were randomly allocated to 3 groups: a 6-beat-kick group (K6), a 4-beat-kick group (K4), and a control group (CG). Biomechanical and physiological parameters were evaluated during a 400-m swim and a 10-minute cycle segment before (Pretraining) and after (Posttraining) the program. A lower stroke frequency ( p = 0.004) and a higher stroke length ( p = 0.002) was found in K6 compared with CG at Posttraining. A reduction in the K6 emerged between Pretraining and Posttraining during cycling for heart rate ( p = 0.005), V̇O 2 ( p = 0.014), and energy expenditure ( p = 0.008). A positive association emerged between swim kick index and cycling cadence in the K6 group. The improvement in stroke frequency and length observed in the K6 group could be explained as an improvement in swimming technique. Similarly, the reduction in energy expenditure during cycling at Posttraining for the K6 group suggests an improvement in the working economy. Triathlon coaches and athletes should consider the inclusion of high swim kick into their training programs to enhance swim and cycling performance, which can ultimately lead to an improvement in the swim-to-cycle transition and the overall triathlon performance.

Low serum brain-derived neurotrophic factor may predict poor response to cardiac rehabilitation in patients with cardiovascular disease.

BACKGROUND: It has been shown that serum brain-derived neurotrophic factor (BDNF) is associated with skeletal muscle energy metabolism and that BDNF is a predictor of mortality in heart failure patients. However, little is known about the relationship between BDNF and cardiac rehabilitation (CR). Therefore, this study retrospectively investigated the effects of baseline serum BDNF levels on the CR-induced exercise capacity improvement in patients with cardiovascular disease (CVD). METHODS: We assigned 99 CVD patients (mean age 71±12 years, male = 60) to Low, Middle, and High groups based on the tertiles of baseline BDNF levels. Cardiopulmonary exercise testing was done using supervised bicycle ergometer twice before and after 3 weeks of CR. Analysis of covariance (ANCOVA) followed by post-hoc analysis using Tukey's HSD test was conducted to assess the multivariate associations between baseline BDNF levels categorized by BDNF tertiles (as independent variable) and %increases in AT and peak VO2 after 3-week CR (as dependent variables) after adjustment for age and gender (as covariates), as a main statistical analysis of the present study. RESULTS: The higher the baseline BDNF levels, the better nutritional status evaluated by the CONUT score (p<0.0001). Baseline anaerobic threshold (AT) and peak oxygen uptake (peak VO2) were similar among the three groups. ANCOVA followed by post-hoc analysis revealed that age- and gender-adjusted %increases in peak VO2 after 3-week CR were positively associated with baseline BDNF levels (p = 0.0239) and Low BDNF group showed significantly lower %increase in peak VO2 than High BDNF group (p = 0.0197). Significant association was not found between baseline BDNF and %increase in AT (p = 0.1379). CONCLUSIONS: Low baseline BDNF levels were associated with malnutrition in CVD patients. A positive association between baseline BDNF levels and CR-induced increases in peak VO2 was found. It was suggested that CVD patients with low baseline BDNF levels may be poor responders to CR.

Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.