The mechanisms underpinning the slow component of [Formula: see text] in humans.

PURPOSE: When exercising above the lactic threshold (LT), the slow component of oxygen uptake ([Formula: see text]) appears, mainly ascribed to the progressive recruitment of Type II fibers. However, also the progressive decay of the economy of contraction may contribute to it. We investigated oxygen uptake ([Formula: see text]) during isometric contractions clamping torque (T) or muscular activation to quantify the contributions of the two mechanisms. METHODS: We assessed for 7 min T of the leg extensors, net oxygen uptake ([Formula: see text]) and root mean square (RMS) from vastus lateralis (VL) in 11 volunteers (21 ± 2 yy; 1.73 ± 0.11 m; 67 ± 14 kg) during cyclic isometric contractions (contraction/relaxation 5 s/5 s): (i) at 65% of maximal voluntary contraction (MVC) (FB-Torque) and; (ii) keeping the level of RMS equal to that at 65% of MVC (FB-EMG). RESULTS: [Formula: see text] after the third minute in FB-Torque increased with time ([Formula: see text] = 94 × t + 564; R2 = 0.99; P = 0.001), but not during FB-EMG. [Formula: see text]/T increased only during FB-Torque ([Formula: see text]/T = 1.10 × t + 0.57; R2 = 0.99; P = 0.001). RMS was larger in FB-Torque than in FB-EMG and significantly increased in the first three minutes of exercise to stabilize till the end of the trial, indicating that the pool of recruited MUs remained constant despite [Formula: see text]. CONCLUSION: The analysis of the RMS, [Formula: see text] and T during FB-Torque suggests that the intrinsic mechanism attributable to the decay of contraction efficiency was responsible for an increase of [Formula: see text] equal to 18% of the total [Formula: see text].

Current definitions of the breathing cycle in alveolar breath-by-breath gas exchange analysis.

Identification of the breathing cycle forms the basis of any breath-by-breath gas exchange analysis. Classically, the breathing cycle is defined as the time interval between the beginning of two consecutive inspiration phases. Based on this definition, several research groups have developed algorithms designed to estimate the volume and rate of gas transferred across the alveolar membrane ("alveolar gas exchange"); however, most algorithms require measurement of lung volume at the beginning of the ith breath (VLi-1; i.e., the end-expiratory lung volume of the preceding ith breath). The main limitation of these algorithms is that direct measurement of VLi-1 is challenging and often unavailable. Two solutions avoid the requirement to measure VLi-1 by redefining the breathing cycle. One method defines the breathing cycle as the time between two equal fractional concentrations of lung expired oxygen (Fo2) (or carbon dioxide; Fco2), typically in the alveolar phase, whereas the other uses the time between equal values of the Fo2/Fn2 (or Fco2/Fn2) ratios [i.e., the ratio of fractional concentrations of lung expired O2 (or CO2) and nitrogen (N2)]. Thus, these methods identify the breathing cycle by analyzing the gas fraction traces rather than the gas flow signal. In this review, we define the traditional approach and two alternative definitions of the human breathing cycle and present the rationale for redefining this term. We also explore the strengths and limitations of the available approaches and provide implications for future studies.

Effect of recovery time on [Formula: see text]-ON kinetics in humans at the onset of moderate-intensity cycling exercise.

PURPOSE: τ of the primary phase of [Formula: see text] kinetics during square-wave, moderate-intensity exercise mirrors that of PCr splitting (τPCr). Pre-exercise [PCr] and the absolute variations of PCr (∆[PCr]) occurring during transient have been suggested to control τPCr and, in turn, to modulate [Formula: see text] kinetics. In addition, [Formula: see text] kinetics may be slower when exercise initiates from a raised metabolic level, i.e., from a less-favorable energetic state. We verified the hypothesis that: (i) pre-exercise [PCr], (ii) pre-exercise metabolic rate, or (iii) ∆[PCr] may affect the kinetics of muscular oxidative metabolism and, therefore, τ. METHODS: To this aim, seven active males (23.0 yy ± 2.3; 1.76 m ± 0.06, [Formula: see text]: 3.32 L min-1 ± 0.67) performed three repetitions of series consisting of six 6-min step exercise transitions of identical workload interspersed with different times of recovery: 30, 60, 90, 120, 300 s. RESULTS: Mono-exponential fitting was applied to breath-by-breath [Formula: see text], so that τ was determined. τ decays as a first-order exponential function of the time of recovery (τ = 109.5 × e(-t/14.0) + 18.9 r2 = 0.32) and linearly decreased as a function of the estimated pre-exercise [PCr] (τ = - 1.07 [PCr] + 44.9, r2 = 0.513, P < 0.01); it was unaffected by the estimated ∆[PCr]. CONCLUSIONS: Our results in vivo do not confirm the positive linear relationship between τ and pre-exercise [PCr] and ∆[PCr]. Instead, [Formula: see text] kinetics seems to be influenced by the pre-exercise metabolic rate and the altered intramuscular energetic state.

The Effect of Endurance Training on Pulmonary V˙O2 Kinetics in Solid Organs Transplanted Recipients.

Background: We investigated the effects of single (SL-ET) and double leg (DL-ET) high-intensity interval training on O2 deficit (O2Def) and mean response time (MRT) during square-wave moderate-intensity exercise (DL-MOD), and on the amplitude of V˙O2p slow component (SCamp), during heavy intensity exercise (DL-HVY), on 33 patients (heart transplant = 13, kidney transplanted = 11 and liver transplanted = 9). Methods: Patients performed DL incremental step exercise to exhaustion, two DL-MOD tests, and a DL-HVY trial before and after 24 sessions of SL-ET (n = 17) or DL-ET (n = 16). Results: After SL-ET, O2Def, MRT and SCamp decreased by 16.4% ± 13.7 (p = 0.008), by 15.6% ± 13.7 (p = 0.004) and by 35% ± 31 (p = 0.002), respectively. After DL-ET, they dropped by 24.9% ± 16.2 (p < 0.0001), by 25.9% ± 13.6 (p < 0.0001) and by 38% ± 52 (p = 0.0003), respectively. The magnitude of improvement of O2Def, MRT, and SCamp was not significantly different between SL-ET and DL-ET after training. Conclusions: We conclude that SL-ET is as effective as DL-ET if we aim to improve V˙O2p kinetics in transplanted patients and suggest that the slower, V˙O2p kinetics is mainly caused by the impairment of peripherals exchanges likely due to the immunosuppressive medications and disuse.

COVID-19 disease in professional football players: symptoms and impact on pulmonary function and metabolic power during matches.

This study aimed at: (1) Reporting COVID-19 symptoms and duration in professional football players; (2) comparing players' pulmonary function before and after COVID-19; (3) comparing players' metabolic power (Pmet ) before and after COVID-19. Thirteen male players (Age: 23.9 ± 4.0 years, V̇O2peak : 49.7 ± 4.0 mL/kg/min) underwent a medical screening and performed a running incremental step test and a spirometry test after COVID-19. Spirometric data were compared with the ones collected at the beginning of the same season. Players' mean Pmet of the 10 matches played before COVID-19 was compared with mean Pmet of the 10 matches played after COVID-19. Players completed a questionnaire on COVID-19 symptoms and duration 6 months following the disease. COVID-19 positivity lasted on average 15 ± 5 days. "General fatigue" and "muscle fatigue" symptoms were reported by all players during COVID-19 and persisted for 77% (general fatigue) and 54% (muscle fatigue) of the players for 37 ± 28 and 38 ± 29 days after the disease, respectively. No significant changes in spirometric measurements were found after COVID-19, even though some impairments at the individual level were observed. Conversely, a linear mixed-effects model analysis showed a significant reduction of Pmet (-4.1 ± 3.5%) following COVID-19 (t = -2.686, p < 0.05). "General fatigue" and "muscle fatigue" symptoms may persist for several weeks following COVID-19 in professional football players and should be considered for a safer return to sport. Players' capacity to compete at high intensities might be compromised after COVID-19.

Modeling V̇o2 on-kinetics based on intensity-dependent delayed adjustment and loss of efficiency (DALE).

This study presents and evaluates a new mathematical model of V̇o2 on-kinetics, with the following properties: 1) a progressively slower primary phase following the size-principle of motor unit recruitment, explaining the delayed V̇o2 steady state seen in the heavy exercise intensity domain, and 2) a severe-domain slow component modeled as a time-dependent decrease in efficiency. Breath-by-breath V̇o2 measurements from eight subjects performing step cycling transitions, in the moderate, heavy, and severe exercise domains, were fitted to the conventional three-phase model and the new model. Model performance was evaluated with a residual analysis and by comparing Bayesian (BIC) and corrected Akaike (AICc) information criteria. The residual analysis showed no systematic deviations, except perhaps for the initial part of the primary phase. BIC favored the new model, being 9.3 (SD 7.1) lower than the conventional model whereas AICc was similar between models. Compared with the conventional three-phase model, the proposed model distinguishes between the kinetic adaptations in the heavy and severe domains by predicting a delayed steady-state V̇o2 in the heavy and no steady-state V̇o2 in the severe domain. This allows to determine when stable oxygen costs of exercise are attainable and it also represents a first step in defining time-dependent oxygen costs when stable energy conversion efficiency is not attainable.NEW & NOTEWORTHY We propose and assess a new minimalistic integrated model for the V̇o2 on-kinetics, inspired by the currently available best evidence of the underlying mechanisms. We show that the model provides a similar fit as the conventionally used three-phase model, even though a stricter data fitting method is used for the proposed model. The proposed model clarifies misconceptions related to the V̇o2 slow component's behavior, by clearly predicting that steady-state V̇o2 is attainable in the moderate and heavy exercise intensity domains. Furthermore, the model opens new possibilities for assessing oxygen cost during severe intensity exercise without the fallible assumption of time-constant energy-conversion efficiency.

Effects of 150- and 450-mL Acute Blood Losses on Maximal Oxygen Uptake and Exercise Capacity.

PURPOSE: This study investigated whether maximal oxygen uptake (V˙O2max) and exercise capacity are affected by small acute blood loss (150 mL) and elucidated compensatory mechanisms. METHODS: Thirteen male subjects (V˙O2max, 63 ± 9 mL·kg-1·min-1; mean ± SD) performed incremental exercise to exhaustion on a cycle ergometer in three experimental conditions: in euvolemia (control; blood volume [BV], 6.0 ± 0.7 L) and immediately after acute BV reductions of 150 mL (BVR150mL) and 450 mL (BVR450mL). Changes in plasma volume (PV) and BV during exercise were calculated from hematocrit, hemoglobin concentration, and hemoglobin mass (carbon monoxide rebreathing). RESULTS: The reduction in V˙O2max per milliliter of BVR was 2.5-fold larger after BVR450mL compared with BVR150mL (-0.7 ± 0.3 vs -0.3 ± 0.6 mL·min-1·mL-1, P = 0.029). V˙O2max was not significantly changed after BVR150mL (-1% ± 2%, P = 0.124) but reduced by 7% ± 3% after BVR450mL (P < 0.001) compared with control. Peak power output only decreased after BVR450mL (P < 0.001). At maximal exercise, BV was restored after BVR150mL compared with control (-50 ± 185 mL, P = 0.375) attributed to PV restoration, which was, however, insufficient in restoring BV after BVR450mL (-281 ± 184 mL, P < 0.001). The peak heart rate tended to increase (3 ± 5 bpm, P = 0.062), whereas the O2 pulse (-2 ± 1 mL per beat, P < 0.001) and vastus lateralis tissue oxygenation index (-4% ± 8% points, P = 0.080) were reduced after BVR450mL, suggesting decreased stroke volume and increased leg O2 extraction. CONCLUSION: The deteriorations of V˙O2max and of maximal exercise capacity accelerate with the magnitude of acute blood loss, likely because of a rapid PV restoration sufficient to establish euvolemia after a small but not after a moderate blood loss.

Effect of small vs large muscle mass endurance training on maximal oxygen uptake in organ transplanted recipients.

Maximal oxygen consumption (V̇O2max) is impaired in heart (HTx), kidney (KTx), and liver (LTx) transplanted recipients and the contribution of the cardiovascular, central, and peripheral (muscular) factors in affecting V̇O2max improvement after endurance training (ET) has never been quantified in these patients. ET protocols involving single leg cycling (SL) elicit larger improvements of the peripheral factors affecting O2 diffusion and utilization than the double leg (DL) cycling ET. Therefore, this study aimed to compare the effects of SL-ET vs DL-ET on V̇O2max. We determined the DL-V̇O2max and maximal cardiac output before and after 24 SL-ET vs DL-ET sessions on 33 patients (HTx = 13, KTx = 11 and LTx = 9). The DL-V̇O2max increased by 13.8% ± 8.7 (p < 0.001) following the SL-ET, due to a larger maximal O2 systemic extraction; meanwhile, V̇O2max in DL-ET increased by 18.6% ± 12.7 (p < 0.001) because of concomitant central and peripheral adaptations. We speculate that in transplanted recipients, SL-ET is as effective as DL-ET to improve V̇O2max and that the impaired peripheral O2 extraction and/or utilization play an important role in limiting V̇O2max in these types of patients. Novelty: SL-ET increases V̇O2max in transplanted recipients because of improved peripheral O2 extraction and/or utilization. SL-ET is as successful as DL-ET to improve the cardiorespiratory fitness in transplanted recipients. The model of V̇O2max limitation indicates the peripheral factors as a remarkable limitation to the V̇O2max in these patients.

The effects of sinusoidal linear drifts on the estimation of cardiorespiratory dynamic parameters during sinusoidal workload forcing: a simulation study.

This study aimed at investigating whether: 1) different sinusoidal linear drifts would affect the estimation of the dynamic parameters amplitude (A) and phase lag (φ) of minute ventilation (V˙E), oxygen uptake, carbon dioxide production and heart rate (HR) sinusoidal responses when the frequency analysis technique (F) is performed; 2) the Marquardt-Levenberg non-linear fitting technique (ML) would provide more precise estimations of A and φ of drifted sinusoidal responses compared to F. For each cardiorespiratory variable, fifteen responses to sinusoidal forcing of different sinusoidal periods were simulated by using a first-order dynamic linear model. A wide range of linear drifts were subsequently applied. A and φ were computed for all drifted and non-drifted responses by using both F (AF and φF) and ML (AML and φML). For non-drifted responses, no differences between AF vs AML and φF vs φML were found. Whereas AF and φF were affected by the sinusoidal linear drifts, AML and φML were not. Significant interaction effects (technique x drift) were found for A (P <  0.001; ƞP2 > 0.247) and φ (P <  0.001; ƞP2 > 0.851). Higher goodness of fit values were observed when using ML for drifted V˙E and HR responses only. The present findings suggest ML as a recommended technique to use when sinusoidal linear drifts occur during sinusoidal exercise, and provide new insights on how to analyse drifted cardiorespiratory sinusoidal responses.

Full characterisation of knee extensors' function in ageing: effect of sex and obesity.

BACKGROUND/OBJECTIVES: Muscle function is a marker of current and prospective health/independence throughout life. The effects of sex and obesity (OB) on the loss of muscle function in ageing remain unresolved, with important implications for the diagnosis/monitoring of sarcopenia. To characterise in vivo knee extensors' function, we compared muscles torque and power with isometric and isokinetic tests in older men (M) and women (W), with normal range (NW) of body mass index (BMI) and OB. SUBJECTS/METHODS: In 70 sedentary older M and W (69 ± 5 years), NW and OB (i.e. BMI < 30 kg m-2 and ≥30 kg m-2, respectively) we tested the right knee's extensor: (i) isometric torque at 30°, 60°, 75° and 90° knee angles, and (ii) isokinetic concentric torque at 60, 90, 150, 180 and 210° s-1 angular speeds. Maximal isometric T-angle, maximal isokinetic knee-extensor torque-velocity, theoretical maximal shortening velocity, maximal power, optimal torque and velocity were determined in absolute units, normalised by body mass (BM) and right leg lean mass (LLMR) and compared over sex, BMI categories and angle or angular speeds by three-way ANOVA. RESULTS: In absolute units, relative to BM and LLMR, sex differences were found in favour of M for all parameters of muscle function (main effect for sex, p < 0.05). OB did not affect either absolute or relative to LLMR isometric and isokinetic muscle function (main effect for BMI, p > 0.05); however, muscle function indices, when adjusted for BM, were lower in both M and W with OB compared to NW counterparts (p < 0.05). CONCLUSIONS: We confirmed sex differences in absolute, relative to BM and LLMR muscle function in favour of men. While overall muscle function and muscle contractile quality is conserved in individuals with class I OB, muscle function normalised for BM, which defines the ability to perform independently and safely the activities of daily living, is impaired in comparison with physiological ageing.

Increased oxygen extraction and mitochondrial protein expression after small muscle mass endurance training.

When exercising with a small muscle mass, the mass-specific O2 delivery exceeds the muscle oxidative capacity resulting in a lower O2 extraction compared with whole-body exercise. We elevated the muscle oxidative capacity and tested its impact on O2 extraction during small muscle mass exercise. Nine individuals conducted six weeks of one-legged knee extension (1L-KE) endurance training. After training, the trained leg (TL) displayed 45% higher citrate synthase and COX-IV protein content in vastus lateralis and 15%-22% higher pulmonary oxygen uptake ( V ˙ O 2 peak ) and peak power output ( W ˙ peak ) during 1L-KE than the control leg (CON; all P < .05). Leg O2 extraction (catheters) and blood flow (ultrasound Doppler) were measured while both legs exercised simultaneously during 2L-KE at the same submaximal power outputs (real-time feedback-controlled). TL displayed higher O2 extraction than CON (main effect: 1.7 ± 1.6% points; P = .010; 40%-83% of W ˙ peak ) with the largest between-leg difference at 83% of W ˙ peak (O2 extraction: 3.2 ± 2.2% points; arteriovenous O2 difference: 7.1 ± 4.8 mL· L-1 ; P < .001). At 83% of W ˙ peak , muscle O2 conductance (DM O2 ; Fick law of diffusion) and the equilibration index Y were higher in TL (P < .01), indicating reduced diffusion limitations. The between-leg difference in O2 extraction correlated with the between-leg ratio of citrate synthase and COX-IV (r = .72-.73; P = .03), but not with the difference in the capillary-to-fiber ratio (P = .965). In conclusion, endurance training improves O2 extraction during small muscle mass exercise by elevating the muscle oxidative capacity and the recruitment of DM O2, especially evident during high-intensity exercise exploiting a larger fraction of the muscle oxidative capacity.

Contribution of oxygen extraction fraction to maximal oxygen uptake in healthy young men.

We analysed the importance of systemic and peripheral arteriovenous O2 difference ( a-v¯O2 difference and a-vf O2 difference, respectively) and O2 extraction fraction for maximal oxygen uptake ( V˙O2max ). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion versus perfusion limitations vary with V˙O2max . Articles (n = 17) publishing individual data (n = 154) on V˙O2max , maximal cardiac output ( Q˙max ; indicator-dilution or the Fick method), a-v¯O2 difference (catheters or the Fick equation) and systemic O2 extraction fraction were identified. For the peripheral responses, group-mean data (articles: n = 27; subjects: n = 234) on leg blood flow (LBF; thermodilution), a-vf O2 difference and O2 extraction fraction (arterial and femoral venous catheters) were obtained. Q˙max and two-LBF increased linearly by 4.9-6.0 L · min-1 per 1 L · min-1 increase in V˙O2max (R2  = .73 and R2  = .67, respectively; both P < .001). The a-v¯O2 difference increased from 118-168 mL · L-1 from a V˙O2max of 2-4.5 L · min-1 followed by a reduction (second-order polynomial: R2  = .27). After accounting for a hypoxemia-induced decrease in arterial O2 content with increasing V˙O2max (R2  = .17; P < .001), systemic O2 extraction fraction increased up to ~90% ( V˙O2max : 4.5 L · min-1 ) with no further change (exponential decay model: R2  = .42). Likewise, leg O2 extraction fraction increased with V˙O2max to approach a maximal value of ~90-95% (R2  = .83). Muscle O2 diffusing capacity and the equilibration index Y increased linearly with V˙O2max (R2  = .77 and R2  = .31, respectively; both P < .01), reflecting decreasing O2 diffusional limitations and accentuating O2 delivery limitations. In conclusion, although O2 delivery is the main limiting factor to V˙O2max , enhanced O2 extraction fraction (≥90%) contributes to the remarkably high V˙O2max in endurance-trained individuals.

Blood volume expansion does not explain the increase in peak oxygen uptake induced by 10 weeks of endurance training.

PURPOSE: The endurance training (ET)-induced increases in peak oxygen uptake ([Formula: see text]O2peak) and cardiac output ([Formula: see text]peak) during upright cycling are reversed to pre-ET levels after removing the training-induced increase in blood volume (BV). We hypothesised that ET-induced improvements in [Formula: see text]O2peak and [Formula: see text]peak are preserved following phlebotomy of the BV gained with ET during supine but not during upright cycling. Arteriovenous O2 difference (a-[Formula: see text]O2diff; [Formula: see text]O2/[Formula: see text]), cardiac dimensions and muscle morphology were studied to assess their role for the [Formula: see text]O2peak improvement. METHODS: Twelve untrained subjects ([Formula: see text]O2peak: 44 ± 6 ml kg-1 min-1) completed 10 weeks of supervised ET (3 sessions/week). Echocardiography, muscle biopsies, haemoglobin mass (Hbmass) and BV were assessed pre- and post-ET. [Formula: see text]O2peak and [Formula: see text]peak during upright and supine cycling were measured pre-ET, post-ET and immediately after Hbmass was reversed to the individual pre-ET level by phlebotomy. RESULTS: ET increased the Hbmass (3.3 ± 2.9%; P = 0.005), BV (3.7 ± 5.6%; P = 0.044) and [Formula: see text]O2peak during upright and supine cycling (11 ± 6% and 10 ± 8%, respectively; P ≤ 0.003). After phlebotomy, improvements in [Formula: see text]O2peak compared with pre-ET were preserved in both postures (11 ± 4% and 11 ± 9%; P ≤ 0.005), as was [Formula: see text]peak (9 ± 14% and 9 ± 10%; P ≤ 0.081). The increased [Formula: see text]peak and a-[Formula: see text]O2diff accounted for 70% and 30% of the [Formula: see text]O2peak improvements, respectively. Markers of mitochondrial density (CS and COX-IV; P ≤ 0.007) and left ventricular mass (P = 0.027) increased. CONCLUSION: The ET-induced increase in [Formula: see text]O2peak was preserved despite removing the increases in Hbmass and BV by phlebotomy, independent of posture. [Formula: see text]O2peak increased primarily through elevated [Formula: see text]peak but also through a widened a-[Formula: see text]O2diff, potentially mediated by cardiac remodelling and mitochondrial biogenesis.

High Intensity Interval Training Does Not Have Compensatory Effects on Physical Activity Levels in Older Adults.

BACKGROUND: Exercise has beneficial effects on older adults, but controversy surrounds the purported "compensatory effects" that training may have on total daily physical activity and energy expenditure in the elderly. We wanted to determine whether 8 weeks of high-intensity interval training (HIIT) induced such effects on physical activity and energy expenditure in healthy, active older adult men. METHODS: Twenty-four healthy elderly male volunteers were randomized to two groups. The experimental group performed HIIT (7 × 2 min cycling repetitions, 3 d/w); the control group performed continuous moderate-intensity training (20-30 min cycling, 3 d/w). Physical activity and energy expenditure were measured with a multisensor activity monitor SenseWear Armband Mini. RESULTS: During HIIT, significant changes were observed in moderate and vigorous physical activity, average daily metabolic equivalents (METs), physical activity level, and activity energy expenditure (p < 0.05) but not in total energy expenditure. Sleep and sedentary time, and levels of light physical activity remained constant during the training period. CONCLUSIONS: The findings suggest that HIIT induced no compensatory effect: HIIT does not adversely affect lifestyle, as it does not reduce daily energy expenditure and/or increase sedentary time.