A single chemotherapy administration induces muscle atrophy, mitochondrial alterations and apoptosis in breast cancer patients.

BACKGROUND: Breast cancer patients are commonly treated with sequential administrations of epirubicin-cyclophosphamide (EC) and paclitaxel (TAX). The chronic effect of this treatment induces skeletal muscle alterations, but the specific effect of each chemotherapy agent is unknown. This study aimed to investigate the effect of EC or TAX administration on skeletal muscle homeostasis in breast cancer patients. METHODS: Twenty early breast cancer patients undergoing EC followed by TAX chemotherapies were included. Two groups of 10 women were established and performed vastus lateralis skeletal muscle biopsies either before the first administration (pre) of EC (50 ± 14 years) or TAX (50 ± 16 years) and 4 days later (post). Mitochondrial respiratory capacity recording, reactive oxygen species production, western blotting and histological analyses were performed. RESULTS: Decrease in muscle fibres cross-sectional area was only observed post-EC (-25%; P < 0.001), associated with a reduction in mitochondrial respiratory capacity for the complex I (CI)-linked substrate state (-32%; P = 0.001), oxidative phosphorylation (OXPHOS) by CI (-35%; P = 0.002), CI&CII (-26%; P = 0.022) and CII (-24%; P = 0.027). If H2 O2 production was unchanged post-EC, an increase was observed post-TAX for OXPHOS by CII (+25%; P = 0.022). We found a decrease in makers of mitochondrial content, as shown post-EC by a decrease in the protein levels of citrate synthase (-53%; P < 0.001) and VDAC (-39%; P < 0.001). Despite no changes in markers of mitochondrial fission, a decrease in the expression of a marker of mitochondrial inner-membrane fusion was found post-EC (OPA1; -60%; P < 0.001). We explored markers of mitophagy and found reductions post-EC in the protein levels of PINK1 (-63%; P < 0.001) and Parkin (-56%; P = 0.005), without changes post-TAX. An increasing trend in Bax protein level was found post-EC (+96%; P = 0.068) and post-TAX (+77%; P = 0.073), while the Bcl-2 level was decreased only post-EC (-52%; P = 0.007). If an increasing trend in TUNEL-positive signal was observed post-EC (+68%; P = 0.082), upregulation was highlighted post-TAX (+86%; P < 0.001), suggesting activation of the apoptosis process. CONCLUSIONS: We demonstrated that a single administration of EC induced, in only 4 days, skeletal muscle atrophy and mitochondrial alterations in breast cancer patients. These alterations were characterized by reductions in mitochondrial function and content as well as impairment of mitochondrial dynamics and an increase in apoptosis. TAX administration did not worsen these alterations as this group had already received EC during the preceding weeks. However, it resulted in an increased apoptosis, likely in response to the increased H2 O2 production.

Exacerbated central fatigue and reduced exercise capacity in early-stage breast cancer patients treated with chemotherapy.

PURPOSE: The present study aimed to characterize the etiology of exercise-induced neuromuscular fatigue and its consequences on the force-duration relationship to provide mechanistic insights into the reduced exercise capacity characterizing early-stage breast cancer patients. METHODS: Fifteen early-stage breast cancer patients and fifteen healthy women performed 60 maximal voluntary isometric quadriceps contractions (MVCs, 3 s of contraction, 2 s of relaxation). The critical force was determined as the mean force of the last six contractions, while W' was calculated as the force impulse generated above the critical force. Quadriceps muscle activation during exercise was estimated from vastus lateralis, vastus medialis and rectus femoris EMG. Central and peripheral fatigue were quantified via changes in pre- to postexercise quadriceps voluntary activation (ΔVA) and quadriceps twitch force (ΔQTw) evoked by supramaximal electrical stimulation, respectively. RESULTS: Early-stage breast cancer patients demonstrated lower MVC than controls preexercise (- 15%, P = 0.022), and this reduction persisted throughout the 60-MVC exercise (- 21%, P = 0.002). The absolute critical force was lower in patients than in controls (144 ± 29N vs. 201 ± 47N, respectively, P < 0.001), while W' was similar (P = 0.546), resulting in lower total work done (- 23%, P = 0.001). This was associated with lower muscle activation in the vastus lateralis (P < 0.001), vastus medialis (P = 0.003) and rectus femoris (P = 0.003) in patients. Immediately following exercise, ΔVA showed a greater reduction in patients compared to controls (- 21.6 ± 13.3% vs. - 12.6 ± 7.7%, P = 0.040), while ΔQTw was similar (- 60.2 ± 13.2% vs. - 52.8 ± 19.4%, P = 0.196). CONCLUSION: These findings support central fatigue as a primary cause of the reduction in exercise capacity characterizing early-stage breast cancer patients treated with chemotherapy. CLINICAL TRIALS REGISTRATION: No. NCT04639609-November 20, 2020.

Early skeletal muscle deconditioning and reduced exercise capacity during (neo)adjuvant chemotherapy in patients with breast cancer.

BACKGROUND: Fatigue is a hallmark of breast cancer and is associated with skeletal muscle deconditioning. If cancer-related fatigue occurs early during chemotherapy (CT), the development of skeletal muscle deconditioning and its effect on exercise capacity remain unclear. The aim of this study was to investigate the evolution of skeletal muscle deconditioning and exercise capacity in patients with early-stage breast cancer during CT. METHODS: Patients with breast cancer had a visit before undergoing CT, at 8 weeks, and at the end of chemotherapy (post-CT). Body composition was determined through bioelectrical impedance analysis. Knee extensor, handgrip muscle force and fatigue was quantified by performing maximal voluntary isometric contractions and exercise capacity using the 6-min walking test. Questionnaires were also administered to evaluate quality of life, cancer-related fatigue, and physical activity level. RESULTS: Among the 100 patients, reductions were found in muscle mass (-2.3%, p = .002), exercise capacity (-6.7%, p < .001), and knee extensor force (-4.9%, p < .001) post-CT, which occurred within the first 8 weeks of treatment with no further decrease thereafter. If muscle fatigue did not change, handgrip muscle force decreased post-CT only (-2.5%, p = .001), and exercise capacity continued to decrease between 8 weeks and post-CT (-4.6%, p < .001). Quality of life and cancer-related fatigue were impaired after 8 weeks (p < .001) and remained stable thereafter, whereas the physical activity level remained stable during chemotherapy. CONCLUSIONS: Similar to cancer-related fatigue, skeletal muscle deconditioning and reduced exercise capacity occurred early during breast cancer CT. Thus, it appears essential to prevent these alterations through exercise training implemented during CT.

Development of skeletal muscle atrophy and intermuscular adipose tissue in patients with early breast cancer treated with chemotherapy.

Chemotherapy is a common therapy to treat patients with breast cancer but also leads to skeletal muscle deconditioning. Skeletal muscle deconditioning is multifactorial and intermuscular adipose tissue (IMAT) accumulation is closely linked to muscle dysfunction. To date, there is no clinical study available investigating IMAT development through a longitudinal protocol and the underlying mechanisms remain unknown. Our study was dedicated to investigating IMAT content in patients with early breast cancer who were treated with chemotherapy and exploring the subsequent cellular mechanisms involved in its development. We included 13 women undergoing chemotherapy. Muscle biopsies and ultrasonography assessment were performed before and after chemotherapy completion. Histological and Western blotting analyses were conducted. We found a substantial increase in protein levels of three mature adipocyte markers (perilipin, +901%; adiponectin, +135%; FABP4, +321%; P < 0.05). These results were supported by an increase in oil red O-positive staining (+358%; P < 0.05). A substantial increase in PDGFRα protein levels was observed (+476%; P < 0.05) highlighting an increase in fibro-adipogenic progenitors (FAPs) content. The cross-sectional area of the vastus lateralis muscle fibers substantially decreased (-21%; P < 0.01), and muscle architecture was altered, as shown by a decrease in fascicle length (-15%; P < 0.05) and a decreasing trend in muscle thickness (-8%; P = 0.08). We demonstrated both IMAT development and muscle atrophy in patients with breast cancer who were treated with chemotherapy. FAPs, critical stem cells inducing both IMAT development and skeletal muscle atrophy, also increased, suggesting that FAPs likely play a critical role in the skeletal muscle deconditioning observed in patients with breast cancer who were treated with chemotherapy.

Exercise-Induced Fatigue in Hamstring versus Quadriceps Muscles and Consequences on the Torque-Duration Relationship in Men.

PURPOSE: The present study investigated the mechanisms of neuromuscular fatigue in quadriceps and hamstring muscles and its consequences on the torque-duration relationship. METHODS: Twelve healthy men performed a 5-min all-out exercise (3-s contraction, 2-s relaxation) with either quadriceps or hamstring muscles on separate days. Central fatigue and peripheral fatigue were quantified via changes in pre- to postexercise voluntary activation (VA) and potentiated twitch (P Tw ) torque evoked by supramaximal electrical stimulation, respectively. Critical torque was determined as the mean torque of the last six contractions, whereas W ' was calculated as the torque impulse done above critical torque. RESULTS: After exercise, maximal voluntary contraction (MVC) decreased to a greater magnitude ( P < 0.001) in quadriceps (-67% ± 9%) compared with hamstring (-51% ± 10%). ∆P Tw was also greater in quadriceps compared with hamstring (-69% ± 15% vs 55% ± 10%, P < 0.01), whereas central fatigue only developed in quadriceps (∆VA, -25% ± 28%). Hamstring demonstrated reduced critical torque compared with quadriceps (60 ± 12 vs 97 ± 26 N·m, P < 0.001) as well as drastically lower W ' (1001 ± 696 vs 8111 ± 2073 N·m·s, P < 0.001). No correlation was found between quadriceps and hamstring for any index of neuromuscular fatigue (∆MVC, ∆P Tw , or ∆VA). CONCLUSIONS: These findings revealed that hamstring presented different etiology and magnitude of neuromuscular fatigue compared with quadriceps. The absence of correlation observed between quadriceps and hamstring fatigue parameters (∆MVC, ∆P Tw , or ∆VA) suggests no interrelation in fatigue etiology between these two muscle groups within individuals and, therefore, highlights the need to investigate specifically hamstring muscle fatigue.

Chemotherapy impairs skeletal muscle mitochondrial homeostasis in early breast cancer patients.

BACKGROUND: Chemotherapy is extensively used to treat breast cancer and is associated with skeletal muscle deconditioning, which is known to reduce patients' quality of life, treatment efficiency, and overall survival. To date, skeletal muscle mitochondrial alterations represent a major aspect explored in breast cancer patients; nevertheless, the cellular mechanisms remain relatively unknown. This study was dedicated to investigating overall skeletal muscle mitochondrial homeostasis in early breast cancer patients undergoing chemotherapy, including mitochondrial quantity, function, and dynamics. METHODS: Women undergoing (neo)adjuvant anthracycline-cyclophosphamide and taxane-based chemotherapy participated in this study (56 ± 12 years). Two muscle biopsies were collected from the vastus lateralis muscle before the first and after the last chemotherapy administration. Mitochondrial respiratory capacity, reactive oxygen species production, and western blotting analyses were performed. RESULTS: Among the 11 patients, we found a decrease in key markers of mitochondrial quantity, reaching -52.0% for citrate synthase protein levels (P = 0.02) and -38.2% for VDAC protein levels (P = 0.04). This mitochondrial content loss is likely explained by reduced mitochondrial biogenesis, as evidenced by a decrease in PGC-1α1 protein levels (-29.5%; P = 0.04). Mitochondrial dynamics were altered, as documented by a decrease in MFN2 protein expression (-33.4%; P = 0.01), a key marker of mitochondrial outer membrane fusion. Mitochondrial fission is a prerequisite for mitophagy activation, and no variation was found in either key markers of mitochondrial fission (Fis1 and DRP1) or mitophagy (Parkin, PINK1, and Mul1). Two contradictory hypotheses arise from these results: defective mitophagy, which probably increases the number of damaged and fragmented mitochondria, or a relative increase in mitophagy through elevated mitophagic potential (Parkin/VDAC ratio; +176.4%; P < 0.02). Despite no change in mitochondrial respiratory capacity and COX IV protein levels, we found an elevation in H2 O2 production (P < 0.05 for all substrate additions) without change in antioxidant enzymes. We investigated the apoptosis pathway and found an increase in the protein expression of the apoptosis initiation marker Bax (+72.0%; P = 0.04), without variation in the anti-apoptotic protein Bcl-2. CONCLUSIONS: This study demonstrated major mitochondrial alterations subsequent to chemotherapy in early breast cancer patients: (i) a striking reduction in mitochondrial biogenesis, (ii) altered mitochondrial dynamics and potential mitophagy defects, (iii) exacerbated H2 O2 production, and (iv) increased initiation of apoptosis. All of these alterations likely explain, at least in part, the high prevalence of skeletal muscle and cardiorespiratory deconditioning classically observed in breast cancer patients.

Energy Cost of Running in Well-Trained Athletes: Toward Slope-Dependent Factors.

PURPOSE: This study aimed to determine the contribution of metabolic, cardiopulmonary, neuromuscular, and biomechanical factors to the energy cost (ECR) of graded running in well-trained runners. METHODS: Eight men who were well-trained trail runners (age: 29 [10] y, mean [SD]; maximum oxygen consumption: 68.0 [6.4] mL·min-1·kg-1) completed maximal isometric evaluations of lower limb extensor muscles and 3 randomized trials on a treadmill to determine their metabolic and cardiovascular responses and running gait kinematics during downhill (DR: -15% slope), level (0%), and uphill running (UR: 15%) performed at similar O2 uptake (approximately 60% maximum oxygen consumption). RESULTS: Despite similar O2 demand, ECR was lower in DR versus level running versus UR (2.5 [0.2] vs 3.6 [0.2] vs 7.9 [0.5] J·kg-1·m-1, respectively; all P < .001). Energy cost of running was correlated between DR and level running conditions only (r2 = .63; P = .018). Importantly, while ECR was correlated with heart rate, cardiac output, and arteriovenous O2 difference in UR (all r2 > .50; P < .05), ECR was correlated with lower limb vertical stiffness, ground contact time, stride length, and step frequency in DR (all r2 > .58; P < .05). Lower limb isometric extension torques were not related to ECR whatever the slope. CONCLUSION: The determining physiological factors of ECR might be slope specific, mainly metabolic and cardiovascular in UR versus mainly neuromuscular and mechanical in DR. This possible slope specificity of ECR during incline running opens the way for the implementation of differentiated physiological evaluations and training strategies to optimize performance in well-trained trail runners.

Physiological factors determining downhill vs uphill running endurance performance.

OBJECTIVES: Recent studies investigated the determinants of trail running performance (i.e., combining uphill (UR) and downhill running sections (DR)), while the possible specific physiological factors specifically determining UR vs DR performances (i.e., isolating UR and DR) remain presently unknown. This study aims to determine the cardiorespiratory responses to outdoor DR vs UR time-trial and explore the determinants of DR and UR performance in highly trained runners. DESIGN: Randomized controlled trial. METHODS: Ten male highly-trained endurance athletes completed 5-km DR and UR time-trials (average grade: ±8%) and were tested for maximal oxygen uptake, lower limb extensor maximal strength, local muscle endurance, leg musculotendinous stiffness, vertical jump ability, explosivity/agility and sprint velocity. Predictors of DR and UR performance were investigated using correlation and commonality regression analyses. RESULTS: Running velocity was higher in DR vs UR time-trial (20.4±1.0 vs 12.0±0.5km·h-1, p<0.05) with similar average heart rate (95±2% vs 94±2% maximal heart rate; p>0.05) despite lower average V̇O2 (85±8% vs 89±7% V̇O2max; p<0.05). Velocity at V̇O2max (vV̇O2max) body mass index (BMI) and maximal extensor strength were significant predictors of UR performance (r2=0.94) whereas vV̇O2max, leg musculotendinous stiffness and maximal extensor strength were significant predictors of DR performance (r2=0.84). CONCLUSIONS: Five-km UR and DR running performances are both well explained by three independent predictors. If two predictors are shared between UR and DR performances (vV̇O2max and maximal strength), their relative contribution is different and, importantly, the third predictor appears very specific to the exercise modality (BMI for UR vs leg musculotendinous stiffness for DR).

Small-Sided Games Are Not as Effective as Intermittent Running to Stimulate Aerobic Metabolism in Prepubertal Soccer Players.

PURPOSE: The purpose of this study was to investigate the influence of the soccer pitch area during small-sided games (SSG) in prepubertal children on physiological and technical demands, and to compare them, for the physiological demands, to high-intensity interval training (HIIT). METHODS: Ten young soccer players (13.0 [0.3] y) performed a HIIT and 3 SSG of various field sizes (30 × 20 m, 42 × 38 m, and 51 × 34 m). Each SSG was performed with 5 players per team, during 4 × 4-minutes interspaced with 1 minute of passive recovery in between. HIIT also followed a 4 × 4-minute protocol with running speed set on an individual basis. Heart rate (HR) was continuously monitored during training sessions. For each exercise modality, time spent above 90% of HRmax (T≥90%,HRmax) was calculated, and technical actions were quantified during SSG by video analysis. RESULTS: T≥90%,HRmax was similar between the 3 SSG (∼587 [276] s; P > .2) but 24% to 37% lower than during HIIT (826 [140] s, P < .05). Coefficients of variations in T≥90%,HRmax were 2.3 to 3.5 times larger in SSG compared with HIIT. For technical actions, greater number of possessions (21 [6] vs ∼14 [4]), and lower ball touches per possession (2.4 [0.6] vs ∼2.9 [0.6]) were found in the small SSG compared with larger SSG, respectively (P < .05). CONCLUSION: The 3 SSG led to lower acute stimulation of the aerobic metabolism, suggesting a lower potential for chronic aerobic adaptations, compared with HIIT. Moreover, interindividual variability in the physiological response was substantially greater in SSG compared with HIIT, indicating increased heterogeneity among players performing the same training protocol.

High-intensity downhill running exacerbates heart rate and muscular fatigue in trail runners.

This study explores the cardiorespiratory and muscular fatigue responses to downhill (DR) vs uphill running (UR) at similar running speed or similar oxygen uptake (⩒O2). Eight well-trained, male, trail runners completed a maximal level incremental test and three 15-min treadmill running trials at ±15% slope: i) DR at ~6 km·h-1 and ~19% ⩒O2max (LDR); ii) UR at ~6 km·h-1 and ~70% ⩒O2max (HUR); iii) DR at ~19 km·h-1 and ~70% ⩒O2max (HDR). Cardiorespiratory responses and spatiotemporal gait parameters were measured continuously. Maximal isometric torque was assessed before and after each trial for hip and knee extensors and plantar flexor muscles. At similar speed (~6 km·h-1), cardiorespiratory responses were attenuated in LDR vs HUR with altered running kinematics (all p < 0.05). At similar ⩒O2 (~3 l·min-1), heart rate, pulmonary ventilation and breathing frequency were exacerbated in HDR vs HUR (p < 0.01), with reduced torque in knee (-15%) and hip (-11%) extensors and altered spatiotemporal gait parameters (all p < 0.01). Despite submaximal metabolic intensity (70% ⩒O2max), heart rate and respiratory frequency reached maximal values in HDR. These results further our understanding of the particular cardiorespiratory and muscular fatigue responses to DR and provide the bases for future DR training programs for trail runners.

Evolution of Physical Status From Diagnosis to the End of First-Line Treatment in Breast, Lung, and Colorectal Cancer Patients: The PROTECT-01 Cohort Study Protocol.

Background: Cancer cachexia and exacerbated fatigue represent two hallmarks in cancer patients, negatively impacting their exercise tolerance and ultimately their quality of life. However, the characterization of patients' physical status and exercise tolerance and, most importantly, their evolution throughout cancer treatment may represent the first step in efficiently counteracting their development with prescribed and tailored exercise training. In this context, the aim of the PROTECT-01 study will be to investigate the evolution of physical status, from diagnosis to the end of first-line treatment, of patients with one of the three most common cancers (i.e., lung, breast, and colorectal). Methods: The PROTECT-01 cohort study will include 300 patients equally divided between lung, breast and colorectal cancer. Patients will perform a series of assessments at three visits throughout the treatment: (1) between the date of diagnosis and the start of treatment, (2) 8 weeks after the start of treatment, and (3) after the completion of first-line treatment or at the 6-months mark, whichever occurs first. For each of the three visits, subjective and objective fatigue, maximal voluntary force, body composition, cachexia, physical activity level, quality of life, respiratory function, overall physical performance, and exercise tolerance will be assessed. Discussion: The present study is aimed at identifying the nature and severity of maladaptation related to exercise intolerance in the three most common cancers. Therefore, our results should contribute to the delineation of the needs of each group of patients and to the determination of the most valuable exercise interventions in order to counteract these maladaptations. This descriptive and comprehensive approach is a prerequisite in order to elaborate, through future interventional research projects, tailored exercise strategies to counteract specific symptoms that are potentially cancer type-dependent and, in fine, to improve the health and quality of life of cancer patients. Moreover, our concomitant focus on fatigue and cachexia will provide insightful information about two factors that may have substantial interaction but require further investigation. Trial registration: This prospective study has been registered at ClinicalTrials.gov (NCT03956641), May, 2019.

Trail Runners Cannot Reach V˙O2max during a Maximal Incremental Downhill Test.

PURPOSE: The purpose of this study was twofold: (i) determine if well-trained athletes can achieve similar peak oxygen uptake (V˙O2peak) in downhill running (DR) versus level running (LR) or uphill running (UR) and (ii) investigate if lower limb extensor muscle strength is related to the velocity at V˙O2peak (vV˙O2peak) in DR, LR, and UR. METHODS: Eight athletes (V˙O2max = 68 ± 2 mL·min·kg) completed maximal incremental tests in LR, DR (-15% slope), and UR (+15% slope) on a treadmill (+1, +1.5, and +0.5 km·h every 2 min, respectively) while cardiorespiratory responses and spatiotemporal running parameters were continuously measured. They were also tested for maximal voluntary isometric strength of hip and knee extensors and plantar flexors. RESULTS: Oxygen uptake at maximal effort was approximately 16% to 18% lower in DR versus LR and UR (~57 ± 2 mL·min·kg, 68 ± 2 mL·min·kg, and 70 ± 3 mL·min·kg, respectively) despite much greater vV˙O2peak (22.7 ± 0.6 km·h vs 18.7 ± 0.5 km·h and 9.3 ± 0.3 km·h, respectively). At vV˙O2peak, longer stride length and shorter contact time occurred in DR versus LR and UR (+12%, +119%, -38%, and -61%, respectively). Contrary to knee extensor and plantar flexor, hip extensor isometric strength correlated to vV˙O2peak in DR, LR, and UR (r = -0.86 to -0.96, P < 0.05). At similar V˙O2, higher heart rate and ventilation emerged in DR versus LR and UR, associated with a more superficial ventilation pattern. CONCLUSIONS: This study demonstrates that well-trained endurance athletes, accustomed to DR, achieved lower V˙O2peak despite higher vV˙O2peak during DR versus LR or UR maximal incremental tests. The specific heart rate and ventilation responses in DR might originate from altered running gait and increased lower-limb musculotendinous mechanical loading, furthering our understanding of the particular physiology of DR, ultimately contributing to optimize trail race running performance.

Cardiorespiratory Responses to Downhill Versus Uphill Running in Endurance Athletes.

PURPOSE: Mountain running races are becoming increasingly popular, although our understanding of the particular physiology associated with downhill running (DR) in trained athletes remains scarce. This study explored the cardiorespiratory responses to high-slope constant velocity uphill running (UR) and DR. METHOD: Eight endurance athletes performed a maximal incremental test and 2 15-min running bouts (UR, +15%, or DR, -15%) at the same running velocity (8.5 ± 0.4 km·h-1). Oxygen uptake ([Formula: see text]O2), heart rate (HR), and ventilation rates ([Formula: see text]E) were continuously recorded, and blood lactate (bLa) was measured before and after each trial. RESULTS: Downhill running induced a more superficial [Formula: see text]E pattern featuring reduced tidal volume (p < .05, ES = 6.05) but similar respiratory frequency (p > .05, ES = 0.68) despite lower [Formula: see text]E (p < .05, ES = 5.46), [Formula: see text]O2 (p < .05, ES = 12.68), HR (p < .05, ES = 6.42), and bLa (p < .05, ES = 1.70). A negative slow component was observed during DR for [Formula: see text]O2 (p < .05, ES = 1.72) and HR (p < .05, ES = 0.80). CONCLUSIONS: These results emphasize the cardiorespiratory responses to DR and highlight the need for cautious interpretation of [Formula: see text]O2, HR, and [Formula: see text]E patterns as markers of exercise intensity for training load prescription and management.

High-intensity interval training combined with resistance training improves physiological capacities, strength and quality of life in multiple sclerosis patients: a pilot study.

BACKGROUND: Numerous studies have shown that mild-to-moderate intensity or resistance exercise training improves physical capacities such as, peak oxygen consumption, maximal tolerated power and strength in multiple sclerosis patients. However, few studies have evaluated the effects of high-intensity interval training (HIIT) associated to with resistance training. Only few studies have analyzed difference between men and women before and after combined training. Moreover, the evaluation of exercise between ambulatory multiple sclerosis patients without disability (Expanded Disability Status Score [EDSS] 0-3) and patients with disabilities (EDSS 3.5-5) was not largely published. AIM: The main objective of our study was to determine if HIIT combined with resistance training improved aerobic and strength capacities as well as quality of life in multiple sclerosis patients and if gender and disabilities play a role in these changes. DESIGN: This study was an open-label uncontrolled study. SETTING: The study was performed outside from conventional care facilities and including homebased training. POPULATION: Twenty-six multiple sclerosis patients have completed the program (19 women, 7 men; mean age 44.6±7.9 years, EDSS 2 [0-5]). METHODS: We conducted a 12-week program of high-intensity interval training combined with resistance training at body weight. Peak oxygen consumption, maximal tolerated power, lactates, isokinetic strength of quadriceps and hamstrings (at 90°/s, 180°/s, and 240°/s) and quality of life were evaluated before and after the program. RESULTS: Peak oxygen consumption and maximum tolerated power improved by 13.5% and 9.4%, respectively. Isokinetic muscle strength increased in both quadriceps and hamstrings at each speed, with a rebalancing of strength between the two legs in quadriceps. Quality of life was also enhanced in three domains. Women showed better improvements than men in V̇O2peak, maximal tolerated power, lactates at the end of test, and heart rate peak, strength in both quadriceps and hamstrings mostly at low speed, and quality of life. The two EDSS groups increased V̇O2peak and strength. CONCLUSIONS: Our study has shown that HIIT combined with resistance exercise training induced an improvement in physical capacity and quality of life. Moreover, this study allowed patients, irrespective of their sex or EDSS score, to resume exercise autonomously. CLINICAL REHABILITATION IMPACT: The results of the study showed that aerobic training at moderate intensity is not the single type of training tolerated by multiple sclerosis patients. High-intensity interval training is well tolerated too and can be used in clinical rehabilitation with resistance training, in both men and women with and without disabilities.

Moderate Exercise Allows for shorter Recovery Time in Critical Limb Ischemia.

Whether and how moderate exercise might allow for accelerated limb recovery in chronic critical limb ischemia (CLI) remains to be determined. Chronic CLI was surgically induced in mice, and the effect of moderate exercise (training five times per week over a 3-week period) was investigated. Tissue damages and functional scores were assessed on the 4th, 6th, 10th, 20th, and 30th day after surgery. Mice were sacrificed 48 h after the last exercise session in order to assess muscle structure, mitochondrial respiration, calcium retention capacity, oxidative stress and transcript levels of genes encoding proteins controlling mitochondrial functions (PGC1α, PGC1ß, NRF1) and anti-oxidant defenses markers (SOD1, SOD2, catalase). CLI resulted in tissue damages and impaired functional scores. Mitochondrial respiration and calcium retention capacity were decreased in the ischemic limb of the non-exercised group (Vmax = 7.11 ± 1.14 vs. 9.86 ± 0.86 mmol 02/min/g dw, p < 0.001; CRC = 7.01 ± 0.97 vs. 11.96 ± 0.92 microM/mg dw, p < 0.001, respectively). Moderate exercise reduced tissue damages, improved functional scores, and restored mitochondrial respiration and calcium retention capacity in the ischemic limb (Vmax = 9.75 ± 1.00 vs. 9.82 ± 0.68 mmol 02/min/g dw; CRC = 11.36 ± 1.33 vs. 12.01 ± 1.24 microM/mg dw, respectively). Exercise also enhanced the transcript levels of PGC1α, PGC1ß, NRF1, as well as SOD1, SOD2, and catalase. Moderate exercise restores mitochondrial respiration and calcium retention capacity, and it has beneficial functional effects in chronic CLI, likely by stimulating reactive oxygen species-induced biogenesis and anti-oxidant defenses. These data support further development of exercise therapy even in advanced peripheral arterial disease.

Downhill exercise training in monocrotaline-injected rats: Effects on echocardiographic and haemodynamic variables and survival.

BACKGROUND: Eccentric exercise training has been shown to improve muscle force strength without excessive cardiovascular stress. Such an exercise modality deserves to be tested in pulmonary arterial hypertension. AIM: We aimed to assess the effects of an eccentric training modality on cardiac function and survival in an experimental monocrotaline-induced model of pulmonary arterial hypertension with right ventricular dysfunction. METHODS: Forty rats were randomly assigned to one of four groups: 40mg/kg monocrotaline-injected sedentary rats; 40mg/kg monocrotaline-injected eccentric-trained rats; sedentary control rats; or eccentric-trained control rats. Eccentric exercise training consisted of downhill running on a treadmill with a -15° slope for 30minutes, 5 days a week for 4 weeks. Training tolerance was assessed by echocardiography, right ventricle catheterization and the rats' maximal eccentric speed. RESULTS: Survival in monocrotaline-injected eccentric-trained rats was not different from that in monocrotaline-injected sedentary rats. Monocrotaline-injected eccentric-trained rats tolerated this training modality well, and haemodynamic status did not deteriorate further compared with monocrotaline-injected sedentary rats. The eccentric maximal speed decline was less pronounced in trained compared with sedentary pulmonary arterial hypertension rats. CONCLUSIONS: Eccentric exercise training had no detrimental effects on right heart pressure, cardiac function and survival in rats with stable monocrotaline-induced pulmonary hypertension.

Cardio-respiratory responses to hypoxia combined with CO2 inhalation during maximal exercise.

We measured the effects of adding CO2 to an inhaled hypoxic gas mixture on cardio-respiratory parameters during maximal exercise. Eight young males performed four incremental maximal exercise tests on cycle under ambient air, hypoxia (FIO2 0.125), inhaled CO2 (FICO2 0.045), and combination of hypoxia and inhaled CO2. The highest ventilation (VE) and VE/CO2 output were recorded in CO2 inhalation and combined treatments. Arterial O2 partial pressure was higher in combined than in hypoxia treatment, but the difference between the treatments narrowed from rest to end-exercise, at least partly because the magnitude of the increase in VE (%) at exercise was smaller in combined treatment than in hypoxia. Arterial O2 content was higher in combined treatment than in hypoxia at rest, but no more at maximal exercise. Cardiac output was higher and O2 extraction lower when breathing O2-poor gas mixtures than under the two other treatments. For a given oxygen consumption, hypoxia and combined treatment showed similar cardiac output and O2 extraction.

Comparative assessment of knee extensor and flexor muscle strength measured using a hand-held vs. isokinetic dynamometer.

[Purpose] To compare measurements of knee extensor and flexor muscle strength performed using a hand-held dynamometer and an isokinetic dynamometer in apparently healthy subjects. [Subjects and Methods] Thirty adult volunteers underwent knee muscle strength evaluation using an isokinetic or a hand-held dynamometer. [Results] Strong positive correlations were found between the 2 methods, with correlation coefficients r ranging from 0.72 (95% confidence interval [CI], 0.48-0.86) to 0.87 (95% CI, 0.75-0.94), depending on the muscle group and the isokinetic evaluation mode. The reproducibility of the hand-held dynamometer findings was good, judged by a coefficient of variation of 3.2-4.2%. However, the correlation between the 2 methods for the assessment of flexor/extensor ratios ranged from -0.04 to 0.46. [Conclusion] Knee extensor and flexor muscle strength recorded with a hand-held dynamometer is reproducible and significantly correlated with the isokinetic values, indicating that this method may in some cases be a useful replacement for isokinetic strength measurement. However, for strength ratio assessment, and when judged against the isokinetic standard, a hand-held dynamometer is not a valid option.