Accurate Prediction Equations for Ventilatory Thresholds in Cardiometabolic Disease When Gas Exchange Analysis is Unavailable: Development and Validation.

AIMS: To develop and validate equations predicting heart rate (HR) at the first and second ventilatory thresholds (VTs) and an optimized range-adjusted prescription for patients with cardiometabolic disease (CMD). To compare their performance against guideline-based exercise intensity domains. METHODS: Cross-sectional study involving 2,868 CMD patients from nine countries. HR predictive equations for first and second VTs (VT1, VT2) were developed using multivariate linear regression with 975 cycle-ergometer cardiopulmonary exercise tests (CPET). 'Adjusted' percentages of peak HR (%HRpeak) and HR reserve (%HRR) were derived from this group. External validation with 1,893 CPET (cycle-ergometer or treadmill) assessed accuracy, agreement, and reliability against guideline-based %HRpeak and %HRR prescriptions using mean absolute percentage error (MAPE), Bland-Altman analyses, intraclass correlation coefficients (ICC). RESULTS: HR predictive equations (R²: 0.77 VT1, 0.88 VT2) and adjusted %HRR (VT1: 42%, VT2: 77%) were developed. External validation demonstrated superiority over widely used guideline-directed intensity domains for %HRpeak and %HRR. The new methods showed consistent performance across both VTs with lower MAPE (VT1: 7.1%, VT2: 5.0%), 'good' ICC for VT1 (0.81, 0.82) and 'excellent' for VT2 (0.93). Guideline-based exercise intensity domains had higher MAPE (VT1: 6.8%-21.3%, VT2: 5.1%-16.7%), 'poor' to 'good' ICC for VT1, and 'poor' to 'excellent' for VT2, indicating inconsistencies related to specific VTs across guidelines. CONCLUSION: Developed and validated HR predictive equations and the optimized %HRR for CMD patients for determining VT1 and VT2 outperformed the guideline-based exercise intensity domains and showed ergometer interchangeability. They offer a superior alternative for prescribing moderate intensity exercise when CPET is unavailable.

Equations to predict heart rate at ventilatory thresholds were developed and externally validated, offering a new perspective when a cardiopulmonary exercise test is unavailable to accurately determine the aerobic exercise intensity domains. Additionally, an adjusted range for exercise intensity prescription based on the percentage of heart rate reserve (%HRR) was provided, utilizing a large sample from eight countries. The proposed equations and the range-adjusted %HRR significantly outperformed the guideline-directed methods for determining exercise intensity, exhibiting higher accuracy, agreement, and reliability. Exercise intensity prescription based on the percentage of heart rate peak showed higher errors, raising concerns about its clinical applicability. Our study may enhance the efficacy of exercise training and physical activity advice when gas exchange analysis is unavailable, potentially leading to improved clinical outcomes, even in low-resource settings. Employing these approaches in research could facilitate more tailored and consistent interventions, introducing a contemporary perspective for studies comparing exercise intensity prescriptions.

Chronotropic incompetence is more frequent in obese adolescents and relates to systemic inflammation and exercise intolerance.

BACKGROUND: Adults with obesity may display disturbed cardiac chronotropic responses during cardiopulmonary exercise testing, which relates to poor cardiometabolic health and an increased risk for adverse cardiovascular events. It is unknown whether cardiac chronotropic incompetence (CI) during maximal exercise is already present in obese adolescents and, if so, how that relates to cardiometabolic health. METHODS: Sixty-nine obese adolescents (body mass index standard deviation score = 2.23 ± 0.32, age = 14.1 ± 1.2 years; mean ± SD) and 29 lean adolescents (body mass index standard deviation score = -0.16 ± 0.84, age = 14.0 ± 1.5 years) performed a maximal cardiopulmonary exercise testing from which indicators for peak performance were determined. The resting heart rate and peak heart rate were used to calculate the maximal chronotropic response index. Biochemistry (lipid profile, glycemic control, inflammation, and leptin) was studied in fasted blood samples and during an oral glucose tolerance test within obese adolescents. Regression analyses were applied to examine associations between the presence of CI and blood or exercise capacity parameters, respectively, within obese adolescents. RESULTS: CI was prevalent in 32 out of 69 obese adolescents (46%) and 3 out of 29 lean adolescents (10%). C-reactive protein was significantly higher in obese adolescents with CI compared to obese adolescents without CI (p = 0.012). Furthermore, peak oxygen uptake and peak cycling power output were significantly reduced (p < 0.05) in obese adolescents with CI vs. obese adolescents without CI. The chronotropic index was independently related to blood total cholesterol (standardized coefficient ß = -0.332; p = 0.012) and C-reactive protein concentration (standardized coefficient ß = -0.269; p = 0.039). CONCLUSION: CI is more common in the current cohort of obese adolescents, and is related to systemic inflammation and exercise intolerance.

Efficacy of 12 weeks oral beta-alanine supplementation in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Beta-alanine (BA) supplementation increases muscle carnosine, an abundant endogenous antioxidant and pH buffer in skeletal muscle. Carnosine loading promotes exercise capacity in healthy older adults. As patients with chronic obstructive pulmonary disease (COPD) suffer from elevated exercise-induced muscle oxidative/carbonyl stress and acidosis, and from reduced muscle carnosine stores, it was investigated whether BA supplementation augments muscle carnosine and induces beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress in patients with COPD. METHODS: In this double-blind, randomized, placebo (PL)-controlled trial (clinicaltrials.gov identifier: NCT02770417), 40 patients (75% male) with COPD (mean ± standard deviation: age 65 ± 6 years; FEV1 % predicted 55 ± 14%) were assigned to 12 weeks oral BA or PL supplementation (3.2 g/day). The primary outcome, i.e. muscle carnosine, was quantified from m. vastus lateralis biopsies obtained before and after intervention. Co-primary outcomes, i.e. incremental and constant work rate cycle capacity, were also assessed. Linear mixed model analyses were performed. Compliance with and side effects of supplement intake and secondary outcomes (quadriceps strength and endurance, and muscle oxidative/carbonyl stress) were also assessed. RESULTS: Beta-alanine supplementation increased muscle carnosine in comparison with PL in patients with COPD (mean difference [95% confidence interval]; +2.82 [1.49-4.14] mmol/kg wet weight; P < 0.001). Maximal incremental cycling capacity (VO2 peak: +0.5 [-0.7 to 1.7] mL/kg/min; P = 0.384, Wpeak: +5 [-1 to 11] W; P = 0.103) and time to exhaustion on the constant work rate cycle test (+28 [-179 to 236] s; P = 0.782) did not change significantly. Compliance with supplement intake was similar in BA (median (quartile 1-quartile 3); 100 (98-100)%) and PL (98 (96-100)%) (P = 0.294) groups, and patients did not report side effects possibly related to supplement intake. No change was observed in secondary outcomes. CONCLUSIONS: Beta-alanine supplementation is efficacious in augmenting muscle carnosine (+54% from mean baseline value) without side effects in patients with COPD in comparison with PL. However, accompanied beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress were not observed.

Altered muscle oxidative phenotype impairs exercise tolerance but does not improve after exercise training in multiple sclerosis.

BACKGROUND: Patients with multiple sclerosis (MS) experience reduced exercise tolerance that substantially reduces quality of life. The mechanisms underpinning exercise intolerance in MS are not fully clear. This study aimed to determine the contributions of the cardiopulmonary system and peripheral muscle in MS-induced exercise intolerance before and after exercise training. METHODS: Twenty-three patients with MS (13 women) and 20 age-matched and sex-matched healthy controls (13 women) performed a cardiopulmonary exercise test. Muscle fibre type composition, size, succinate dehydrogenase (SDH) activity, capillarity, and gene expression and proteins related to mitochondrial density were determined in vastus lateralis muscle biopsies. Nine MS patients (five women) were re-examined following a 12 week exercise training programme consisting of high-intensity cycling interval and resistance training. RESULTS: Patients with MS had lower maximal oxygen uptake compared with healthy controls (V̇O2peak , 25.0 ± 8.5 vs. 35.7 ± 6.4 mL/kg/min, P < 0.001). The lower gas exchange threshold (MS: 14.5 ± 5.5 vs. controls: 19.7 ± 2.9 mL/kg/min, P = 0.01) and slope of V̇O2 versus work rate (MS: 9.5 ± 1.7 vs. controls: 10.8 ± 1.1 mL/min/W, P = 0.01) suggested an intramuscular contribution to exercise intolerance in patients with MS. Muscle SDH activity was 22% lower in MS (P = 0.004), and strongly correlated with several indices of whole-body exercise capacity in MS patients (e.g. V̇O2peak , Spearman's ρ = 0.81, P = 0.002), but not healthy controls (ρ = 0.24, P = 0.38). In addition, protein levels of mitochondrial OXPHOS complexes I (-40%, P = 0.047) and II (-45%, P = 0.026) were lower in MS patients versus controls. Muscle capillary/fibre ratio correlated with V̇O2peak in healthy controls (ρ = 0.86, P < 0.001) but not in MS (ρ = 0.35, P = 0.22), and did not differ between groups (1.41 ± 0.30 vs. 1.47 ± 0.38, P = 0.65). Expression of genes involved in mitochondrial function, such as PPARA, PPARG, and TFAM, was markedly reduced in muscle tissue samples of MS patients (all P < 0.05). No differences in muscle fibre type composition or size were observed between groups (all P > 0.05). V̇O2peak increased by 23% following exercise training in MS (P < 0.001); however, no changes in muscle capillarity, SDH activity, gene or protein expression were observed (all P > 0.05). CONCLUSIONS: Skeletal muscle oxidative phenotype (mitochondrial complex I and II content, SDH activity) is lower in patients with MS, contributing to reduced exercise tolerance. However, skeletal muscle mitochondria appeared resistant to the beneficial effects of exercise training, suggesting that other physiological systems, at least in part, drive the improvements in exercise capacity following exercise training in MS.

Impact of continuous vs. interval training on oxygen extraction and cardiac function during exercise in type 2 diabetes mellitus.

PURPOSE: Exercise training improves exercise capacity in type 2 diabetes mellitus (T2DM). It remains to be elucidated whether such improvements result from cardiac or peripheral muscular adaptations, and whether these are intensity dependent. METHODS: 27 patients with T2DM [without known cardiovascular disease (CVD)] were randomized to high-intensity interval training (HIIT, n = 15) or moderate-intensity endurance training (MIT, n = 12) for 24 weeks (3 sessions/week). Exercise echocardiography was applied to investigate cardiac output (CO) and oxygen (O2) extraction during exercise, while exercise capacity [([Formula: see text] (mL/kg/min)] was examined via cardiopulmonary exercise testing at baseline and after 12 and 24 weeks of exercise training, respectively. Changes in glycaemic control (HbA1c and glucose tolerance), lipid profile and body composition were also evaluated. RESULTS: 19 patients completed 24 weeks of HIIT (n = 10, 66 ± 11 years) or MIT (n = 9, 61 ± 5 years). HIIT and MIT similarly improved glucose tolerance (pTime = 0.001, pInteraction > 0.05), [Formula: see text] (mL/kg/min) (pTime = 0.001, pInteraction > 0.05), and exercise performance (Wpeak) (pTime < 0.001, pInteraction > 0.05). O2 extraction increased to a greater extent after 24 weeks of MIT (56.5%, p1 = 0.009, pTime = 0.001, pInteraction = 0.007). CO and left ventricular longitudinal strain (LS) during exercise remained unchanged (pTime > 0.05). A reduction in HbA1c was correlated with absolute changes in LS after 12 weeks of MIT (r = - 0.792, p = 0.019, LS at rest) or HIIT (r = - 0.782, p = 0.038, LS at peak exercise). CONCLUSION: In patients with well-controlled T2DM, MIT and HIIT improved exercise capacity, mainly resulting from increments in O2 extraction capacity, rather than changes in cardiac output. In particular, MIT seemed highly effective to generate these peripheral adaptations. TRIAL REGISTRATION: NCT03299790, initially released 09/12/2017.

Exercise capacity is related to attenuated responses in oxygen extraction and left ventricular longitudinal strain in asymptomatic type 2 diabetes patients.

AIMS: Type 2 diabetes mellitus (T2DM) is associated with reduced exercise capacity and cardiovascular diseases, both increasing morbidity and risk for premature death. As exercise intolerance often relates to cardiac dysfunction, it remains to be elucidated to what extent such an interplay occurs in T2DM patients without overt cardiovascular diseases. Design: Cross-sectional study, NCT03299790. METHODS AND RESULTS: Fifty-three T2DM patients underwent exercise echocardiography (semi-supine bicycle) with combined ergospirometry. Cardiac output (CO), left ventricular longitudinal strain (LS), oxygen uptake (O2), and oxygen (O2) extraction were assessed simultaneously at rest, low-intensity exercise, and high-intensity exercise. Glycaemic control and lipid profile were assessed in the fasted state. Participants were assigned according to their exercise capacity being adequate or impaired (EXadequate: O2peak <80% and EXimpaired: O2peak ≥80% of predicted O2peak) to compare O2 extraction, CO, and LS at all stages. Thirty-eight participants (EXimpaired: n = 20 and EXadequate: n = 18) were included in the analyses. Groups were similar regarding HbA1c, age, and sex (P > 0.05). At rest, CO was similar in the EXimpaired group vs. EXadequate group (5.1 ± 1 L/min vs. 4.6 ± 1.4 L/min, P > 0.05) and increased equally during exercise. EXimpaired patients displayed a 30.7% smaller increase in O2 extraction during exercise compared to the EXadequate group (P = 0.016) which resulted in a lower O2 extraction at high-intensity exercise (12.5 ± 2.8 mL/dL vs. 15.3 ± 3.9 mL/dL, P = 0.012). Left ventricular longitudinal strain was similar at rest but increased significantly less in the EXimpaired vs. EXadequate patients (1.9 ± 2.5% vs. 5.9 ± 4.1%, P = 0.004). CONCLUSIONS: In asymptomatic T2DM patients, an impaired exercise capacity is associated with an impaired response in oxygen extraction and myocardial deformation (LS). TRIAL REGISTRY: Effect of High-intensity Interval Training on Cardiac Function and Regulation of Glycemic Control in Diabetic Cardiomyopathy (https://clinicaltrials.gov/ct2/show/NCT03299790).

Carnosine quenches the reactive carbonyl acrolein in the central nervous system and attenuates autoimmune neuroinflammation.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease driven by sustained inflammation in the central nervous system. One of the pathological hallmarks of MS is extensive free radical production. However, the subsequent generation, potential pathological role, and detoxification of different lipid peroxidation-derived reactive carbonyl species during neuroinflammation are unclear, as are the therapeutic benefits of carbonyl quenchers. Here, we investigated the reactive carbonyl acrolein and (the therapeutic effect of) acrolein quenching by carnosine during neuroinflammation. METHODS: The abundance and localization of acrolein was investigated in inflammatory lesions of MS patients and experimental autoimmune encephalomyelitis (EAE) mice. In addition, we analysed carnosine levels and acrolein quenching by endogenous and exogenous carnosine in EAE. Finally, the therapeutic effect of exogenous carnosine was assessed in vivo (EAE) and in vitro (primary mouse microglia, macrophages, astrocytes). RESULTS: Acrolein was substantially increased in inflammatory lesions of MS patients and EAE mice. Levels of the dipeptide carnosine (ß-alanyl-L-histidine), an endogenous carbonyl quencher particularly reactive towards acrolein, and the carnosine-acrolein adduct (carnosine-propanal) were ~ twofold lower within EAE spinal cord tissue. Oral carnosine treatment augmented spinal cord carnosine levels (up to > tenfold), increased carnosine-acrolein quenching, reduced acrolein-protein adduct formation, suppressed inflammatory activity, and alleviated clinical disease severity in EAE. In vivo and in vitro studies indicate that pro-inflammatory microglia/macrophages generate acrolein, which can be efficiently quenched by increasing carnosine availability, resulting in suppressed inflammatory activity. Other properties of carnosine (antioxidant, nitric oxide scavenging) may also contribute to the therapeutic effects. CONCLUSIONS: Our results identify carbonyl (particularly acrolein) quenching by carnosine as a therapeutic strategy to counter inflammation and macromolecular damage in MS.

Carnosine and skeletal muscle dysfunction in a rodent multiple sclerosis model.

Muscle weakness and fatigue are primary manifestations of multiple sclerosis (MS), a chronic disease of the central nervous system. Interventions that enhance muscle function may improve overall physical well-being of MS patients. Recently, we described that levels of carnosine, an endogenous muscle dipeptide involved in contractile function and fatigue-resistance, are reduced in muscle tissue from MS patients and a monophasic rodent MS model (experimental autoimmune encephalomyelitis, EAE). In the present study, we aimed to (1) confirm this finding in a chronic EAE model, along with the characterization of structural and functional muscle alterations, and (2) investigate the effect of carnosine supplementation to increase/restore muscle carnosine levels and improve muscle function in EAE. We performed muscle immunohistochemistry and ex vivo contractility measurements to examine muscle structure and function at different stages of EAE, and following nutritional intervention (oral carnosine: 3, 15 or 30 g/L in drinking water). Immunohistochemistry revealed progressively worsening muscle fiber atrophy and a switch towards a fast-twitch muscle phenotype during EAE. Using ex vivo muscle contractility experiments, we observed reductions in muscle strength and contraction speed, but no changes in muscle fatigability of EAE mice. However, carnosine levels were unaltered during all stages of EAE, and even though oral carnosine supplementation dose-dependently increased muscle carnosine levels up to + 94% after 56 days EAE, this did not improve muscle function of EAE mice. In conclusion, EAE mice display significant, yet time-dependent, muscular alterations, and carnosine intervention does not improve muscle function in EAE.

Periodized versus classic exercise therapy in Multiple Sclerosis: a randomized controlled trial.

BACKGROUND: Periodizing exercise interventions in Multiple Sclerosis (MS) shows good high intensity exercise training adherence. Whether this approach induces comparable training adaptations with respect to exercise capacity, body composition and muscle strength compared to conventional, linear progressive training programs however is not known. METHODS: Thirty-one persons with MS (all phenotypes, mean EDSS 2.3±1.3) were randomized into a twelve-week periodized (MSPER, n=17) or a classic endurance (MSCLA, n=14) training program. At baseline (PRE), exercise capacity (maximal exercise test, VO2max), body composition (DEXA) and muscle strength (Biodex®) were assessed. Classic, moderate intensity endurance training (60-80% HRmax, 5 training sessions/2w, 60min/session) was performed on a stationary bicycle. Periodized exercise included 4 recurrent 3-week cycles of alternated endurance training (week 1: endurance training as described above), high intense exercise (week 2: 3 sessions/w, 3 × 20s all-out sprints, 10min/session) and recovery weeks (week 3: one sprint session as described above). POST measurements were performed similar to baseline. Total exercise volume of both programs was expressed as total peak-effort training minutes. RESULTS: For MSCLA, total exercise volume included 1728 total peak-effort training minutes, whereas MSPER included only 736. Despite this substantially reduced training volume, twelve weeks of periodized training significantly (p<0.05) improved VO2max (+14%, p=0.001), workload (+20%) and time until exhaustion (+25%). Classic training significantly (p<0.05) improved workload (+10%) and time until exhaustion (+17%), but not VO2max (+5%, p=0.131). Pre-post improvements for VO2max were significantly higher in MSPER compared to MSCLA (p=0.046). CONCLUSION: These data show that despite substantially lower training time (57% less peak-effort training minutes), 12 weeks of periodized exercise training in persons with MS seems to induce larger improvements in parameters of exercise capacity compared to classic endurance training. We therefore recommend to further investigate the effect of training periodization on various functional rehabilitation measures in MS.

Asymptomatic type 2 diabetes mellitus display a reduced myocardial deformation but adequate response during exercise.

BACKGROUND AND PURPOSE: The development of myocardial fibrosis is a major complication of Type 2 diabetes mellitus (T2DM), impairing myocardial deformation and, therefore, cardiac performance. It remains to be established whether abnormalities in longitudinal strain (LS) exaggerate or only occur in well-controlled T2DM, when exposed to exercise and, therefore, cardiac stress. We therefore studied left ventricular LS at rest and during exercise in T2DM patients vs. healthy controls. METHODS AND RESULTS: Exercise echocardiography was applied with combined breath-by-breath gas exchange analyses in asymptomatic, well-controlled (HbA1c: 6.9 ± 0.7%) T2DM patients (n = 36) and healthy controls (HC, n = 23). Left ventricular LS was assessed at rest and at peak exercise. Peak oxygen uptake (V̇O2peak) and workload (Wpeak) were similar between groups (p > 0.05). Diastolic (E, e's, E/e') and systolic function (left ventricular ejection fraction) were similar at rest and during exercise between groups (p > 0.05). LS (absolute values) was significantly lower at rest and during exercise in T2DM vs. HC (17.0 ± 2.9% vs. 19.8 ± 2% and 20.8 ± 4.0% vs. 23.3 ± 3.3%, respectively, p < 0.05). The response in myocardial deformation (the change in LS from rest up to peak exercise) was similar between groups (+ 3.8 ± 0.6% vs. + 3.6 ± 0.6%, in T2DM vs. HC, respectively, p > 0.05). Multiple regression revealed that HDL-cholesterol, fasted insulin levels and exercise tolerance accounted for 30.5% of the variance in response of myocardial deformation in the T2DM group (p = 0.002). CONCLUSION: Myocardial deformation is reduced in well-controlled T2DM and despite adequate responses, such differences persist during exercise. TRIAL REGISTRATION: NCT03299790, initially released 09/12/2017.

Exercise Training in Patients with Chronic Respiratory Diseases: Are Cardiovascular Comorbidities and Outcomes Taken into Account?-A Systematic Review.

Patients with chronic obstructive pulmonary disease (COPD), asthma and interstitial lung diseases (ILD) frequently suffer from cardiovascular comorbidities (CVC). Exercise training is a cornerstone intervention for the management of these conditions, however recommendations on tailoring programmes to patients suffering from respiratory diseases and CVC are scarce. This systematic review aimed to identify the eligibility criteria used to select patients with COPD, asthma or ILD and CVC to exercise programmes; assess the impact of exercise on cardiovascular outcomes; and identify how exercise programmes were tailored to CVC. PubMed, Scopus, Web of Science and Cochrane were searched. Three reviewers extracted the data and two reviewers independently assessed the quality of studies with the Quality Assessment Tool for Quantitative Studies. MetaXL 5.3 was used to calculate the individual and pooled effect sizes (ES). Most studies (58.9%) excluded patients with both stable and unstable CVC. In total, 26/42 studies reported cardiovascular outcomes. Resting heart rate was the most reported outcome measure (n = 13) and a small statistically significant effect (ES = -0.23) of exercise training on resting heart rate of patients with COPD was found. No specific adjustments to exercise prescription were described. Few studies have included patients with CVC. There was a lack of tailoring of exercise programmes and limited effects were found. Future studies should explore the effect of tailored exercise programmes on relevant outcome measures in respiratory patients with CVC.

Exercise-induced lactate responses in Multiple Sclerosis: A retrospective analysis.

BACKGROUND: Persons with Multiple Sclerosis have elevated resting serum lactate concentrations compared to healthy controls (HC). OBJECTIVE: To evaluate lactate concentrations during acute exercise and/or following training in MS compared to HC. METHODS: In this retrospective study, blood lactate concentrations (mmol/l) originating from two previous studies were analyzed. Lactate concentrations originated from acute submaximal (MSsubmax; HC, n = 11; MS, n = 32) or maximal (MSmax; HC, n = 20; MS, n = 24) exercise tests and following a 24-week mild to moderate intensity (MSsubmax, n = 12) or 12-week high intensity interval (MSmax, n = 13) exercise intervention. RESULTS: Under submaximal conditions in MS and compared to HC, lactaterest (MS: 2.7±0.6 vs HC: 2.3±0.7 was significantly (p < 0.05) elevated. After 24 weeks of mild-to-moderate-intensity exercise training and compared to PRE-values, lactatebout2 (2.5±0.7 vs 3.4±1.1) significantly (p < 0.05) decreased during submaximal testing in MSsubmax. Under maximal conditions, lactatestart (2.3±1.0 vs 1.7±0.9) was significantly (p > 0.05) elevated in MS. Twelve weeks of high intensity interval training did not improve this (p > 0.05). CONCLUSIONS: Under the conditions of this retrospective analysis we conclude that lactate concentrations during acute submaximal and maximal exercise in persons with MS are similar compared to healthy controls. Moderate intensity exercise therapy appeared to improve lactate accumulation but high intensity exercise therapy did not.

Impact of high-intensity concurrent training on cardiovascular risk factors in persons with multiple sclerosis - pilot study.

PURPOSE: High-intensity concurrent training positively affects cardiovascular risk factors. Because this was never investigated in multiple sclerosis, the present pilot study explored the impact of this training on cardiovascular risk factors in this population. METHODS: Before and after 12 weeks of high-intense concurrent training (interval and strength training, 5 sessions per 2 weeks, n = 16) body composition, resting blood pressure and heart rate, 2-h oral glucose tolerance (insulin sensitivity, glycosylated hemoglobin, blood glucose and insulin concentrations), blood lipids (high- and low-density lipoprotein, total cholesterol, triglyceride levels) and C-reactive protein were analyzed. RESULTS: Twelve weeks of high-intense concurrent training significantly improved resting heart rate (-6%), 2-h blood glucose concentrations (-13%) and insulin sensitivity (-24%). Blood pressure, body composition, blood lipids and C-reactive protein did not seem to be affected. CONCLUSIONS: Under the conditions of this pilot study, 12 weeks of concurrent high-intense interval and strength training improved resting heart rate, 2-h glucose and insulin sensitivity in multiple sclerosis but did not affect blood C-reactive protein levels, blood pressure, body composition and blood lipid profiles. Further, larger and controlled research investigating the effects of high-intense concurrent training on cardiovascular risk factors in multiple sclerosis is warranted. Implications for rehabilitation High-intensity concurrent training improves cardiovascular fitness. This pilot study explores the impact of this training on cardiovascular risk factors in multiple sclerosis. Despite the lack of a control group, high-intense concurrent training does not seem to improve cardiovascular risk factors in multiple sclerosis.

Periodized home-based training: A new strategy to improve high intensity exercise therapy adherence in mildly affected patients with Multiple Sclerosis.

INTRODUCTION: Although high intensity exercise therapy (HIT) in Multiple Sclerosis (MS) induces substantial effects, longer term compliance to such a training program is not evident. When embedded in a periodized, home-based training strategy, high intensity exercise therapy adherence may improve. This is explored first in mildly affected persons with MS. METHODS: Exercise capacity (maximal exercise test) and body composition (DEXA) of healthy controls (n = 22) and persons with MS (n = 23, EDSS: 1.9 ±â€¯1.1) were assessed at baseline (PRE). Next and within the context of an MS awareness project (climbing the Mont Ventoux, France), all participants were enrolled in a 6 m home-based periodized HIT oriented cycling program with remote (Polar® M200 activity tracker) supervision. Hereafter, POST measurements were performed similar to baseline. RESULTS: Six months of periodized and home-based HIT oriented training induced improvements in body weight (-3%, p = 0.008), BMI (-3%, p = 0.01), total mass (-2%, p = 0.023), VO2max (+ 5%, p = 0.016), workload (+ 11%, p = 0.001), time until exhaustion (+ 14%, p = 0.001), recovery heart rate (+ 4%, p = 0.04), lactate peak (+ 16%, p = 0.03) and RER (+ 4%, p = 0.04) in MS. Furthermore, all persons with MS safely reached the top of the Mont Ventoux, except for two. CONCLUSION: The applied 6 m periodized, home-based and HIT-oriented cycling program provided good therapy adherence with similar improvements in exercise capacity compared to healthy controls. Furthermore, this exercise regimen trained mildly-affected persons with MS adequately to climb the Mont Ventoux.

Acute responses of cytokines and adipokines to aerobic exercise in relapsing vs. remitting women with multiple sclerosis.

OBJECTIVE: To examine the acute effect of exercise on cytokines and adipokines during relapse and the remitting phase of multiple sclerosis (MS). METHODS: Thirty women with MS in the relapsing or remitting phase were matched with fifteen healthy controls. Participants performed a single-bout of aerobic exercise at 60-70% maximal heart rate. Furthermore, five women in the relapsing phase were enrolled (control relapse) and did not receive any intervention. Blood samples were taken before, immediately after, 1-h and 6-h after the exercise. RESULTS: Levels of IL-10 and TNF-α in response to exercise were similar in healthy and MS remitting subjects. Compared to baseline, TNF-α levels in relapsing subjects were significantly decreased immediately after exercise. Immediately following exercise, leptin levels significantly decreased in relapsing subjects. Adiponectin and IL-6 showed no significant difference between groups. CONCLUSION: After relapse, exercise does not induce inflammatory cytokine response and temporarily improves both cytokine and adipokine balance.

Muscle carnosine in experimental autoimmune encephalomyelitis and multiple sclerosis.

BACKGROUND: Muscle carnosine is related to contractile function (Ca++ handling) and buffering of exercise-induced acidosis. As these muscular functions are altered in Multiple Sclerosis (MS) it is relevant to understand muscle carnosine levels in MS. METHODS: Tibialis anterior muscle carnosine was measured in an animal MS model (EAE, experimental autoimmune encephalomyelitis, n = 40) and controls (CON, n = 40) before and after exercise training (EAEEX, CONEX, 10d, 1 h/d, 24 m/min treadmill running) or sedentary conditions (EAESED, CONSED). Human m. vastus lateralis carnosine of healthy controls (HC, n = 22) and MS patients (n = 24) was measured. RESULTS: EAE muscle carnosine levels were decreased (p < .0001) by ~ 40% to ~ 64% at 10d and 17d following EAE induction (respectively) regardless of exercise (p = .823). Similarly, human MS muscle carnosine levels were decreased (- 25%, p = .03). CONCLUSION: Muscle carnosine concentrations in an animal MS model and MS patients are substantially reduced. In EAE exercise therapy does not restore this.

Elevated cardiovascular risk factors in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is associated with elevated cardiovascular mortality. To prevent this a better understanding of their CVD risk factors and interrelations is necessary. METHODS: MS patients (n = 52) and healthy controls (HC, n = 24) were matched for age, height, weight, body mass index and physical activity. Body composition, resting blood pressure (BP), resting heart rate (HR), glucose tolerance, HbA1c, blood lipids (HDL, LDL, total cholesterol, triglyceride concentrations) and c-reactive protein concentrations were analyzed. Regression analyses identified independent CVD risk factors and their interrelations in MS. RESULTS: In MS and compared to HC, fat mass (25.1 ± 1.2kg vs. 17.9 ± 1kg), fat percentage (33.8 ± 1.2% vs. 28.4 ± 1.5%), systolic (130 ± 1.8mmHg vs. 120 ± 2.9mmHg) and diastolic (79 ± 1.1mmHg vs. 71 ± 1.9mmHg) BP, resting HR (72 ± 1.4bpm vs. 60 ± 2bpm), blood triglycerides (113.8 ± 8.6mg/dl vs. 98.2 ± 17.4mg/dl), fasting (13.5 ± 2.9mU/l vs. 7.2 ± 0.8mU/l) and 2h insulin (71.9 ± 12.5mU/l vs. 35.8 ± 8.1mU/l), 2h glucose (6.3 ± 0.5mmol/l vs. 4.8 ± 0.5mmol/l) and HOMA index (3.7 ± 1.1 vs. 1.7 ± 0.2) were significantly (p < 0.05) elevated. Total cholesterol, blood HDL and LDL concentrations did nog differ between groups (p < 0.05). Regression analyses indicated that MS is independently associated with elevated fat mass/percentage, systolic and diastolic BP and HR and in MS fat mass appears to be an independent contributor of the other measured CVD risk factors in MS. CONCLUSION: Persons with MS have an increased risk for CVD and fat mass appears to be an important risk factor. Therefore, normalizing whole body fat should be an essential part of MS treatment.

High Intensity Training May Reverse the Fiber Type Specific Decline in Myogenic Stem Cells in Multiple Sclerosis Patients.

Multiple sclerosis (MS) is associated with loss of skeletal muscle mass and function. The myogenic stem cells (satellite cells-SCs) are instrumental to accretion of myonuclei, but remain to be investigated in MS. The present study aimed to compare the SC and myonuclei content between MS patients (n = 23) and age matched healthy controls (HC, n = 18). Furthermore, the effects of 12 weeks of high intensity training on SC and myonuclei content were explored in MS. Muscle biopsies were obtained from m. Vastus Lateralis at baseline (MS and HC) and following 12 weeks of training (MS only). Frozen biopsies were sectioned followed by immunohistochemical analysis for fiber type specific SCs (Pax7(+)), myonuclei (MN) and central nuclei content and fiber cross-sectional area (fCSA) was quantified using ATPase histochemistry. At baseline the SCs per fiber was lower in type II compared to type I fibers in both MS (119%, p < 0.01) and HC (69%, p < 0.05), whereas the SCs per fCSA was lower in type II fibers compared to type I only in MS (72%, p < 0.05). No differences were observed in MN or central nuclei between MS and HC. Following training the type II fiber SCs per fiber and per fCSA in MS patients increased by 165% (p < 0.05) and 135% (p < 0.05), respectively. Furthermore, the type II fiber MN content tended (p = 0.06) to be increased by 35% following training. In conclusion, the SC content is lower in type II compared to type I fibers in both MS and HC. Furthermore, high intensity training was observed to selectively increase the SC and myonuclei content in type II fibers in MS patients.

Chronotropic Incompetence During Exercise in Type 2 Diabetes: Aetiology, Assessment Methodology, Prognostic Impact and Therapy.

During incremental exercise tests, chronotropic incompetence (CI), which is the inability of the heart rate (HR) to rise in proportion to an increase in metabolic demand, is often observed in patients with type 2 diabetes mellitus (T2DM). Despite the fact that CI is associated with exercise intolerance and elevated risks of development of cardiovascular disease and premature death, this clinical anomaly is often ignored or overlooked by clinicians and physiologists. CI is, however, a significant clinical abnormality that deserves further attention, examination and treatment. The aetiology of CI in T2DM remains poorly understood and is complex. Certain T2DM-related co-morbidities or physiological anomalies may contribute to development of CI, such as altered blood catecholamine and/or potassium levels during exercise, structural myocardial abnormalities, ventricular and/or arterial stiffness, impaired baroreflex sensitivity and cardiovascular autonomic neuropathy. Clinicians should thus be aware of the potential presence of yet undetected anomalies or diseases in T2DM patients who experience CI during exercise testing. However, an effective treatment for CI in T2DM is yet to be developed. Exercise training programmes seem to be the only potentially effective and feasible interventions for partial restoration of the chronotropic response in T2DM, but it remains poorly understood how these interventions lead to restoration of the chronotropic response. Studies are thus warranted to elucidate the aetiology of CI and develop an effective treatment for CI in T2DM. In particular, the impact of (different) exercise interventions on CI in T2DM deserves greater attention in future studies.

Whole-body cooling does not compromise muscle oxidative capacity in subjects with multiple sclerosis.

BACKGROUND: Whole-body cooling improves exercise tolerance in patients with multiple sclerosis (pwMS). To be able to exercise at greater intensities and/or for longer durations with whole-body cooling, it should be examined whether this compromises skeletal muscle oxidative capacity (assessed by exercise-onset VO2 kinetics). OBJECTIVE: To study the impact of whole-body cooling on exercise-onset VO2 kinetics in pwMS. METHODS: From 12 pwMS (EDSS 3.5 ± 1.5) and 12 healthy age, BMI, and gender-matched subjects exercise-onset VO2 kinetics (mean response time [MRT]) and body temperature were determined under normothermic and hypothermic (pre-exercise 60-min whole-body cooling) conditions during submaximal exercise testing (two 6-min constant-load exercise bouts). Moreover, heart rate, blood lactate content, expiratory volume and ratings of perceived exertion (RPE) were assessed during exercise. RESULTS: Exercise heart rate (-7 ± 6 beats/min) and end-exercise body temperature (-0.9 ± 0.5°C) was significantly lower in hypothermic vs. normothermic conditions in both populations (p < 0.05). In pwMS exercise RPE was lower in hypothermic vs. normothermic condition (p = 0.056). No significantly different MRT was found between normothermic vs. hypothermic conditions in both populations. CONCLUSIONS: Lowering body temperature prior to endurance exercise does not affect muscle oxidative capacity in pwMS, but lowers RPE, thus making it possible to prescribe exercises of greater intensity and/or longer duration.