Relating cardiorespiratory responses to work rate during incremental ramp exercise on treadmill in children and adolescents: sex and age differences

PURPOSE: Evaluation of cardiopulmonary exercise testing (CPET) slopes such as [Formula: see text] (cardiac/skeletal muscle function) and [Formula: see text] (O2 delivery/utilization), using treadmill protocols is limited because the difficulties in measuring the total work rate ([Formula: see text]). To overcome this limitation, we proposed a new method in quantifying [Formula: see text] to determine CPET slopes.METHODS: CPET's were performed by healthy patients, (n=674, 9-18year) 300 female (F) and 374 male (M), using an incremental ramp protocol on a treadmill. For this protocol, a quantitative relationship based on biomechanical principles of human locomotion, was used to quantify the [Formula: see text] of the subject. CPET slopes were determined by linear regression of the data recorded until the gas exchange threshold occurred.RESULTS: The method to estimate [Formula: see text] was substantiated by verifying that: [Formula: see text] for treadmill exercise corresponded to an efficiency of muscular work similar to that of cycle ergometer; [Formula: see text] (mL min-1W-1) was invariant with age and greater in M than F older than 12 years old (13-14years: 9.6±1.5(F) vs. 10.5±1.8(M); 15-16years: 9.7±1.7(F) vs. 10.6±2.2(M); 17-18years: 9.6±1.7(F) vs. 11.0±2.3(M), p<0.05); similar to cycle ergometer exercise, [Formula: see text] was inversely related to body weight (BW) (r=0.71) or [Formula: see text] (r=0.66) and [Formula: see text] was not related to BW (r=- 0.01), but had a weak relationship with [Formula: see text] (r=0.28).CONCLUSION: The proposed approach can be used to estimate [Formula: see text] and quantify CPET slopes derived from incremental ramp protocols at submaximal exercise intensities using the treadmill, like the cycle ergometer, to infer cardiovascular and metabolic function in both healthy and diseased states

Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Oxidative function during exercise was evaluated in 11 young athletes with marked skeletal muscle hypertrophy induced by long-term resistance training (RTA, body mass 102.67.3 kg, meanSD) and 11 controls (CTRL, body mass 77.86.0). Pulmonary O2 uptake (V\u27O2) and vastus lateralis muscle fractional O2 extraction (by near-infrared spectroscopy) were determined during an incremental cycle ergometer (CE) and one-leg knee-extension (KE) exercise. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers obtained by biopsy. Quadriceps femoris muscle cross sectional area, volume (determined by magnetic resonance imaging) and strength were greater in RTA vs. CTRL (by ~40%, ~33% and ~20%, respectively). V\u27O2peak during CE was higher in RTA vs. CTRL (4.050.64 L min-1 vs. 3.560.30)no difference between groups was observed during KE. The O2 cost of CE exercise was not different between groups. When divided per muscle mass (for CE) or quadriceps muscle mass (for KE) V\u27O2peak was lower (by 15-20%) in RTA vs. CTRL. Vastus lateralis fractional O2 extraction was lower in RTA vs. CTRL at all work rates, both during CE and KE. RTA had higher ADP-stimulated mitochondrial respiration (56.723.7 pmolO2s-1mg-1 ww) vs. CTRL (35.710.2), and a tighter coupling of oxidative phosphorylation. In RTA the greater muscle mass and maximal force, and the enhanced mitochondrial respiration seem to compensate for the hypertrophy-induced impaired peripheral O2 diffusion. The net results are an enhanced whole body oxidative function at peak exercise, and unchanged efficiency and O2 cost at submaximal exercise, despite a much greater body mas

Mitochondrial Adaptations in Elderly and Young Men Skeletal Muscle Following 2 Weeks of Bed Rest and Rehabilitation

The aim of the study was to evaluate the expression levels of proteins related to mitochondrial biogenesis regulation and bioenergetics in vastus lateralis muscle biopsies from 16 elderly and 7 young people subjected to 14 days of bed-rest, causing atrophy, and subsequent 14 days of exercise training. Based on quantitative immunoblot analyses, in both groups a reduction of two key regulators of mitochondrial biogenesis/remodeling and activity, namely PGC-1alpha and Sirt3, was revealed during bedrest,with a subsequent up-regulation after rehabilitation, indicating an involvement of PGC-1alpha-Sirt3 axis in response to the treatments. A difference was observed comparing the young and elderly subjects as, for both proteins, the abundance in the elderly was more affected by immobility and less responsive to exercise. The expression levels of TOM20 and Citrate Synthase, assayed as markers of outer mitochondrial membrane and mitochondrial mass, showed a noticeable sensitivity in the elderly group, where they were affected by bed-rest and rehabilitation recalling the pattern of PGC-1alpha. TOM20 and CS remained unchanged in young subjects. Single OXPHOScomplexes showed peculiar patterns, which were in some cases dissimilar from PGC 1alpha, and suggest different influences on protein biogenesis and degradation. Overall,exercise was capable to counteract the effect of immobility, when present, except for complex V, which was markedly downregulated by bed-rest, but remained unaffected after rehabilitation, maybe as result of greater extent of degradation processes over biogenesis. Phosphorylation extent of AMPK, and its upstream activator LKB1, did not change after bed-rest and rehabilitation in either young or elderly subjects, suggestingthat the activation of energy-sensing LKB1-AMPK signaling pathway was \u201cmissed\u201d due to its transient nature, or was not triggered under our conditions. Our study demonstrates that, as far as the expression of various proteins related to mitochondrial biogenesis/remodeling, adaptations to bed-rest and rehabilitation in the two populations were different. The impact of bed-rest was greater in the elderly subjects, where the pattern (decrease after bed rest and recovery following rehabilitation) was accompanied by changes of mitochondrial mass. Modifications of protein abundance were matched with data obtained from gene expression analyses of four public human datasets focusing on related genes

Mitochondrial Adaptations in Elderly and Young Men Skeletal Muscle Following 2 Weeks of Bed Rest and Rehabilitation

The aim of the study was to evaluate the expression levels of proteins related to mitochondrial biogenesis regulation and bioenergetics in vastus lateralis muscle biopsies from 16 elderly and 7 young people subjected to 14 days of bed-rest, causing atrophy, and subsequent 14 days of exercise training. Based on quantitative immunoblot analyses, in both groups a reduction of two key regulators of mitochondrial biogenesis/remodeling and activity, namely PGC-1α and Sirt3, was revealed during bed-rest, with a subsequent up-regulation after rehabilitation, indicating an involvement of PGC-1α-Sirt3 axis in response to the treatments. A difference was observed comparing the young and elderly subjects as, for both proteins, the abundance in the elderly was more affected by immobility and less responsive to exercise. The expression levels of TOM20 and Citrate Synthase, assayed as markers of outer mitochondrial membrane and mitochondrial mass, showed a noticeable sensitivity in the elderly group, where they were affected by bed-rest and rehabilitation recalling the pattern of PGC-1α. TOM20 and CS remained unchanged in young subjects. Single OXPHOS complexes showed peculiar patterns, which were in some cases dissimilar from PGC-1α, and suggest different influences on protein biogenesis and degradation. Overall, exercise was capable to counteract the effect of immobility, when present, except for complex V, which was markedly downregulated by bed-rest, but remained unaffected after rehabilitation, maybe as result of greater extent of degradation processes over biogenesis. Phosphorylation extent of AMPK, and its upstream activator LKB1, did not change after bed-rest and rehabilitation in either young or elderly subjects, suggesting that the activation of energy-sensing LKB1-AMPK signaling pathway was “missed” due to its transient nature, or was not triggered under our conditions. Our study demonstrates that, as far as the expression of various proteins related to mitochondrial biogenesis/remodeling, adaptations to bed-rest and rehabilitation in the two populations were different. The impact of bed-rest was greater in the elderly subjects, where the pattern (decrease after bed rest and recovery following rehabilitation) was accompanied by changes of mitochondrial mass. Modifications of protein abundance were matched with data obtained from gene expression analyses of four public human datasets focusing on related genes

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Respiratory Muscle Interval Training Improves Exercise Capacity in Obese Adolescents during a 3-Week In-Hospital Multidisciplinary Body Weight Reduction Program

The purpose of this study was to determine whether a novel approach of interval training targeted to the respiratory muscles (RMIT; normocapnic hyperpnea with resistance) in addition to a multidisciplinary in-hospital body weight reduction program (BWRP) was able to improve the integrative response to exercise in young patients with obesity. Nine male patients (17.9 ± 4.9 (x ± SD) years; 113.8 ± 16.3 kg) underwent 12 sessions of RMIT and eight age-and sex-matched patients underwent 12 sessions of a sham protocol (CTRL) during the same 3-week BWRP. Before and after the interventions the patients performed an incremental and a heavy-intensity constant work-rate (CWR>GET) cycling exercise to voluntary exhaustion. Body mass decreased by ~4.0 kg after both RMIT (p = 0.0001) and CTRL (p = 0.0002). Peak pulmonary O2 uptake (V˙O2) increased after RMIT (p = 0.02) and CTRL (p = 0.0007). During CWR>GET at ISO-time, V˙O2 (p = 0.0007), pulmonary ventilation (p = 0.01), heart rate (p = 0.02), perceived respiratory discomfort (RPER; p = 0.03) and leg effort (p = 0.0003) decreased after RMIT; only RPER (p = 0.03) decreased after CTRL. Time to exhaustion increased after RMIT (p = 0.0003) but not after CTRL. In young patients with obesity, RMIT inserted in a 3-week BWRP reduced the cardiorespiratory burden, the metabolic cost, the perceived effort, and improved exercise tolerance during heavy-intensity cycling