Extracellular flux analyses reveal differences in mitochondrial PBMC metabolism between high-fit and low-fit females

Analyzing metabolism of peripheral blood mononuclear cells (PBMCs) can possibly serve as a cellular metabolic read-out for lifestyle factors and lifestyle interventions. However, the impact of PBMC composition on PBMC metabolism is not yet clear, neither is the differential impact of a longer-term lifestyle factor versus a short-term lifestyle intervention. We investigated the effect of aerobic fitness level and a recent exercise bout on PBMC metabolism in females. PBMCs from 31 young female adults divided into a high-fit (V̇O2peak ≥ 47 mL/kg/min, N = 15) and low-fit (V̇O2peak ≤ 37 mL/kg/min, N = 16) group were isolated at baseline and overnight after a single bout of exercise (60 minutes, 70% V̇O2peak). Oxygen consumption rate (OCR) and glycolytic rate (GR) were measured using extracellular flux (XF) assays and PBMC subsets were characterized using fluorescence-activated cell sorting (FACS). Basal OCR, FCCP-induced OCR, spare respiratory capacity, ATP-linked OCR, and proton leak were significantly higher in high-fit compared to low-fit females (all P < 0.01), while no significant differences in glycolytic rate (GR) were found (all P > 0.05). A recent exercise bout did not significantly affect GR or OCR parameters (all P > 0.05). The overall PBMC composition was similar between high-fit and low-fit females. Mitochondrial PBMC function was significantly higher in PBMCs from high-fit compared to low-fit females, which was unrelated to PBMC composition and not impacted by a recent bout of exercise. Our study reveals a link between PBMC metabolism and levels of aerobic fitness, increasing the relevance of PBMC metabolism as a marker to study the impact of lifestyle factors on human health.

The H2FPEF and HFA-PEFF algorithms for predicting exercise intolerance and abnormal hemodynamics in heart failure with preserved ejection fraction

Exercise intolerance is a primary manifestation in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with abnormal hemodynamics and a poor quality of life. Two multiparametric scoring systems have been proposed to diagnose HFpEF. This study sought to determine the performance of the H2FPEF and HFA-PEFF scores for predicting exercise capacity and echocardiographic findings of intracardiac pressures during exercise in subjects with dyspnea on exertion referred for bicycle stress echocardiography. In a subset, simultaneous expired gas analysis was performed to measure the peak oxygen consumption (VO2). Patients with HFpEF (n = 83) and controls without HF (n = 104) were enrolled. The H2FPEF score was obtainable for all patients while the HFA-PEFF score could not be calculated for 23 patients (feasibility 88%). Both H2FPEF and HFA-PEFF scores correlated with a higher E/e′ ratio (r = 0.49 and r = 0.46), lower systolic tricuspid annular velocity (r = − 0.44 and = − 0.24), and lower cardiac output (r = − 0.28 and r = − 0.24) during peak exercise. Peak VO2 and exercise duration decreased with an increase in H2FPEF scores (r = − 0.40 and r = − 0.32). The H2FPEF score predicted a reduced aerobic capacity (AUC 0.71, p = 0.0005), but the HFA-PEFF score did not (p = 0.07). These data provide insights into the role of the H2FPEF and HFA-PEFF scores for predicting exercise intolerance and abnormal hemodynamics in patients presenting with exertional dyspnea.

The Relationship Between the Distribution of Training Intensity and Performance of Kayak and Canoe Sprinters: A Retrospective Observational Analysis of One Season of Competition

Purpose: To evaluate retrospectively the training intensity distribution (TID) among highly trained canoe sprinters during a single season and to relate TID to changes in performance.Methods: The heart rates during on-water training by 11 German sprint kayakers (7 women, 4 men) and one male canoeist were monitored during preparation periods (PP) 1 and 2, as well as during the period of competition (CP) (total monitoring period: 37 weeks). The zones of training intensity (Z) were defined as Z1 [&lt;80% of peak oxygen consumption (VO2peak)], Z2 (81–87% VO2peak) and Z3 (&gt;87% VO2peak), as determined by 4 × 1,500-m incremental testing on-water. Prior to and after each period, the time required to complete the last 1,500-m stage (all-out) of the incremental test (1,500-m time-trial), velocities associated with 2 and 4 mmol·L−1 blood lactate (v2[BLa], v4[BLa]) and VO2peak were determined.Results: During each period, the mean TID for the entire group was pyramidal (PP1: 84/12/4%, PP2: 80/12/8% and CP: 91/5/4% for Z1, Z2, Z3) and total training time on-water increased from 5.0 ± 0.9 h (PP1) to 6.1 ± 0.9 h (PP2) and 6.5 ± 1.0 h (CP). The individual ranges for Z1, Z2 and Z3 were 61–96, 2–26 and 0–19%. During PP2 VO2peak (25.5 ± 11.4%) markedly increased compared to PP1 and CP and during PP1 v2[bla] (3.6 ± 3.4%) showed greater improvement compared to PP2, but not to CP. All variables related to performance improved as the season progressed, but no other effects were observed. With respect to time-trial performance, the time spent in Z1 (r = 0.66, p = 0.01) and total time in all three zones (r = 0.66, p = 0.01) showed positive correlations, while the time spent in Z2 (r = −0.57, p = 0.04) was negatively correlated.Conclusions: This seasonal analysis of the effects of training revealed extensive inter-individual variability. Overall, TID was pyramidal during the entire period of observation, with a tendency toward improvement in VO2peak, v2[bla], v4[bla] and time-trial performance. During PP2, when the COVID-19 lockdown was in place, the proportion of time spent in Z3 doubled, while that spent in Z1 was lowered; the total time spent training on water increased; these changes may have accentuated the improvement in performance during this period. A further increase in total on-water training time during CP was made possible by reductions in the proportions of time spent in Z2 and Z3, so that more fractions of time was spent in Z1.

American Ginseng Attenuates Eccentric Exercise-Induced Muscle Damage via the Modulation of Lipid Peroxidation and Inflammatory Adaptation in Males

Exercise-induced muscle damage (EIMD) is characterized by a reduction in functional performance, disruption of muscle structure, production of reactive oxygen species, and inflammatory reactions. Ginseng, along with its major bioactive component ginsenosides, has been widely employed in traditional Chinese medicine. The protective potential of American ginseng (AG) for eccentric EIMD remains unclear. Twelve physically active males (age: 22.4 ± 1.7 years; height: 175.1 ± 5.7 cm; weight: 70.8 ± 8.0 kg; peak oxygen consumption [V˙O2peak] 54.1 ± 4.3 mL/kg/min) were administrated by AG extract (1.6 g/day) or placebo (P) for 28 days and subsequently challenged by downhill (DH) running (−10% gradient and 60% V˙O2peak). The levels of circulating 8-iso-prostaglandin F 2α (PGF2α), creatine kinase (CK), interleukin (IL)-1β, IL-4, IL-10, and TNF-α, and the graphic pain rating scale (GPRS) were measured before and after supplementation and DH running. The results showed that the increases in plasma CK activity induced by DH running were eliminated by AG supplementation at 48 and 72 h after DH running. The level of plasma 8-iso-PGF2α was attenuated by AG supplementation immediately (p = 0.01 and r = 0.53), 2 h (p = 0.01 and r = 0.53) and 24 h (p = 0.028 and r = 0.45) after DH running compared with that by P supplementation. Moreover, our results showed an attenuation in the plasma IL-4 levels between AG and P supplementation before (p = 0.011 and r = 0.52) and 72 h (p = 0.028 and r = 0.45) following DH running. Our findings suggest that short-term supplementation with AG alleviates eccentric EIMD by decreasing lipid peroxidation and promoting inflammatory adaptation.

Physical Fitness as a Prognostic Marker for Infectious Events in Kidney Transplant Recipients

<b><i>Introduction:</i></b> Infectious events are one of the leading causes of death in kidney transplant recipients (KTRs). KTRs have reduced cardiorespiratory fitness (CRF), a predictor for infections in other populations. The aim of this study was to investigate whether CRF and muscle strength are prognostic markers for infectious events in KTRs. <b><i>Methods:</i></b> In this retrospective cohort study, 155 KTRs underwent an incremental, maximal cardiopulmonary exercise test (CPET) 3 months after transplantation. CRF was analyzed with peak oxygen consumption (VO₂ peak) while muscle strength with isometric handgrip (HG) test. Laboratory blood samples and drug therapy were collected. The median follow-up period was 54 (interquartile range 38–62) months. Cox regression analyses were performed to evaluate predictors of infectious events adjusting for potential confounders. <b><i>Results:</i></b> During this study, severe infectious events occurred in 41 subjects (26.5%). 15.5% (<i>n</i> = 24) of patients had a severely reduced CRF, defined as a VO₂ peak below the 5th percentile of the reference values reported for a matched healthy population. The hazard ratio for infectious events in this subgroup was 2.389 (95% CI = 1.188–4.801, <i>p</i> = 0.014), independently of gender, age, BMI, time on dialysis, hemoglobin concentration, eGFR, diabetes, and immunosuppressive regimen. On the contrary, no significant association of HG strength and infections was found. <b><i>Conclusion:</i></b> Therefore, low CRF may be considered as a modifiable predictor of severe infectious events in KTRs. A CPET should thus be recommended for cardiovascular screening, evaluation of CRF, and tailored exercise prescription to reduce the risk of infections and potentially improve long-term outcomes of transplantation.

Circulatory Response to Rapid Volume Expansion and Cardiorespiratory Fitness in Fontan Circulation

The role of dysfunction of the single ventricle in Fontan failure is incompletely understood. We aimed to evaluate hemodynamic responses to preload increase in Fontan circulation, to determine whether circulatory limitations in different locations identified by experimental preload increase are associated with cardiorespiratory fitness (CRF), and to assess the impact of left versus right ventricular morphology. In 38 consecutive patients (median age = 16.6 years, 16 females), heart catheterization was supplemented with a rapid 5-mL/kg body weight volume expansion. Central venous pressure (CVP), ventricular end-diastolic pressure (VEDP), and peak systolic pressure were averaged for 15‒30 s, 45‒120 s, and 4‒6 min (steady state), respectively. CRF was assessed by peak oxygen consumption (VO2peak) and ventilatory threshold (VT). Median CVP increased from 13 mmHg at baseline to 14.5 mmHg (p < 0.001) at steady state. CVP increased by more than 20% in eight patients. Median VEDP increased from 10 mmHg at baseline to 11.5 mmHg (p < 0.001). Ten patients had elevated VEDP at steady state, and in 21, VEDP increased more than 20%. The transpulmonary pressure difference (CVP‒VEDP) and CVP were consistently higher in patients with right ventricular morphology across repeated measurements. CVP at any stage was associated with VO2peak and VT. VEDP after volume expansion was associated with VT. Preload challenge demonstrates the limitations beyond baseline measurements. Elevation of both CVP and VEDP are associated with impaired CRF. Transpulmonary flow limitation was more pronounced in right ventricular morphology. Ventricular dysfunction may contribute to functional impairment after Fontan operation in young adulthood.ClinicalTrials.govidentifier NCT02378857

Mechanical, Cardiorespiratory, and Muscular Oxygenation Responses to Sprint Interval Exercises Under Different Hypoxic Conditions in Healthy Moderately Trained Men

Objective: The aim of this study was to determine the effects of sprint interval exercises (SIT) conducted under different conditions (hypoxia and blood flow restriction [BFR]) on mechanical, cardiorespiratory, and muscular O2 extraction responses.Methods: For this purpose, 13 healthy moderately trained men completed five bouts of 30 s all-out exercises interspaced by 4 min resting periods with lower limb bilateral BFR at 60% of the femoral artery occlusive pressure (BFR60) during the first 2 min of recovery, with gravity-induced BFR (pedaling in supine position; G-BFR), in a hypoxic chamber (FiO2≈13%; HYP) or without additional stress (NOR). Peak and average power, time to achieve peak power, rating of perceived exertion (RPE), and a fatigue index (FI) were analyzed. Gas exchanges and muscular oxygenation were measured by metabolic cart and NIRS, respectively. Heart rate (HR) and peripheral oxygen saturation (SpO2) were continuously recorded.Results: Regarding mechanical responses, peak and average power decreased after each sprint (p &lt; 0.001) excepting between sprints four and five. Time to reach peak power increased between the three first sprints and sprint number five (p &lt; 0.001). RPE increased throughout the exercises (p &lt; 0.001). Of note, peak and average power, time to achieve peak power and RPE were lower in G-BFR (p &lt; 0.001). Results also showed that SpO2 decreased in the last sprints for all the conditions and was lower for HYP (p &lt; 0.001). In addition, Δ[O2Hb] increased in the last two sprints (p &lt; 0.001). Concerning cardiorespiratory parameters, BFR60 application induced a decrease in gas exchange rates, which increased after its release compared to the other conditions (p &lt; 0.001). Moreover, muscle blood concentration was higher for BFR60 (p &lt; 0.001). Importantly, average and peak oxygen consumption and muscular oxyhemoglobin availability during sprints decreased for HYP (p &lt; 0.001). Finally, the tissue saturation index was lower in G-BFR.Conclusions: Thus, SIT associated with G-BFR displayed lower mechanical, cardiorespiratory responses, and skeletal muscle oxygenation than the other conditions. Exercise with BFR60 promotes higher blood accumulation within working muscles, suggesting that BFR60 may additionally affect cellular stress. In addition, HYP and G-BFR induced local hypoxia with higher levels for G-BFR when considering both exercise bouts and recovery periods.

Circulatory Response to Rapid Volume Expansion and Cardiorespiratory Fitness in Fontan Circulation

BackgroundThe role of dysfunction of the single ventricle in Fontan failure is incompletely understood.ObjectivesWe aimed to evaluate haemodynamic responses to preload increase in Fontan circulation, to determine whether circulatory limitations in different locations identified by experimental preload increase are associated with cardiorespiratory fitness (CRF), and to assess the impact of left versus right ventricular morphology.MethodsIn 38 consecutive patients (median age=16.6 years, 16 females), heart catheterisation was supplemented with a rapid 5-mL/kg body weight volume expansion. Central venous pressure (CVP), ventricular end-diastolic pressure (VEDP), and peak systolic pressure were averaged for 15‒30 s, 45‒120 s, and 4‒6 min (steady state), respectively. CRF was assessed by peak oxygen consumption (VO2peak) and ventilatory threshold (VT).ResultsMedian CVP increased from 13 mmHg at baseline to 14.5 mmHg (p<0.001) at steady state. CVP increased by more than 20% in eight patients. Median VEDP increased from 10 mmHg at baseline to 11.5 mmHg (p<0.001). Ten patients had elevated VEDP at steady state, and in 21, VEDP increased more than 20%. The transpulmonary pressure difference (CVP‒VEDP) and CVP were consistently higher in patients with right ventricular morphology across repeated measurements. CVP at any stage was associated with VO2peak and VT. VEDP after volume expansion was associated with VT.ConclusionsPreload challenge demonstrates the limitations beyond baseline measurements. Elevation of both CVP and VEDP are associated with impaired CRF. Transpulmonary flow limitation was more pronounced in right ventricular morphology. Ventricular dysfunction may contribute to functional impairment after Fontan operation in young adulthood.ClinicalTrials.govidentifier: NCT02378857

Heart Rate Recovery at 1 Min after Exercise Is a Marker of Disease Severity and Prognosis in Chronic Thromboembolic Pulmonary Hypertension

<b><i>Background:</i></b> Attenuated heart rate recovery at 1 min (HRR1) was demonstrated to correlate with poor prognosis in patients with pulmonary arterial hypertension, whereas its role in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. <b><i>Objectives:</i></b> The aim of this study was to investigate the correlations between HRR1 and functional status, echocardiography, hemodynamics, and prognosis of CTEPH. <b><i>Methods:</i></b> We retrospectively enrolled patients with CTEPH who underwent right heart catheterization and cardiopulmonary exercise test between June 2014 to October 2020 in Fuwai hospital. The primary outcome was clinical worsening. Linear regression was performed to assess the association between HRR1 and established markers of CTEPH severity. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff of HRR1. Cox regression models were used to assess the association between HRR1 and clinical worsening. <b><i>Results:</i></b> A total of 211 patients with CTEPH were included in the study. After adjusting for confounders, HRR1 positively correlated with 6-min walk distance, mixed venous oxygen saturation, and peak oxygen consumption, and negatively correlated with NT-proBNP, pulmonary vascular resistance, and ventilatory equivalent of carbon dioxide. Compared with patients with HRR1 ≥16 beats, patients with HRR1 &#x3c;16 beats had approximately a 3-fold risk of experiencing clinical worsening and the risk escalated with time. <b><i>Conclusion:</i></b> HRR1 could reflect disease severity and was independently associated with prognosis in patients with CTEPH.

Initial Results From SOMMA: Contribution of Mitochondrial Function to Walking and Fitness

We hypothesize that the capacity of mitochondria in quadriceps skeletal muscle to generate ATP energy by respirometry (OXPHOS) in biopsies from the vastus lateralis, and in whole quadriceps muscle by 31PMRS (ATPmax) would contribute to 4 and 400m gait speed and to peak oxygen consumption on treadmill testing (VO2peak). In analyses from the first SOMMA participants recruited (N=122), OXPHOS was similarly associated with 4m (r=0.21) and 400 m (r=0.21) walking speed (P&lt;0.01). However, ATPmax was not associated with either 4m or 400m walking speed (r=-0.02 and -0.07 respectively). In contrast both OXPHOS (r=0.43) and ATP max (r=0.35) were more strongly correlated with fitness (VO2 peak). These findings suggest that in older people, the mitochondrial capacity to generate ATP plays an important role walking speed and may be even more important to fitness.