Response To Exercise Training Research Articles

Pulmonary rehabilitation in lung transplant candidates with pulmonary arterial hypertension

BackgroundPulmonary rehabilitation (PR) guidelines support the efficacy and safety of supervised exercise training in mild-moderate pulmonary arterial hypertension (PAH). However, the exercise training response and safety of PR in PAH lung transplant (LTx) candidates has not been described. Objectives: (1) characterize the clinical characteristics and illness trajectory of adult patients with severe PAH listed for LTx and participating in PR; (2) evaluate the change in exercise capacity, aerobic and resistance training volumes; (3) assess PR safety. MethodsSingle-centre retrospective cohort study of PAH LTx candidates listed January 2014–December 2018 attending a supervised, facility-based outpatient program three times per week. Functional capacity was evaluated using 6-min walk distance (6MWD). Aerobic and muscle training volumes were evaluated with paired comparisons. Results40 PAH LTx candidates (age 50 ± 12 years, 73% females, mean pulmonary artery pressure 53 ± 16 mmHg) were included. The median listing duration was 91 [IQR 43–232] days. Sixteen patients (40%) had ≥1 admission pre-transplant. Nine patients (56%) were discharged home and resumed outpatient PR. Baseline 6MWD was 330 ± 119 metres (n = 40) with the final 6MWD pre-LTx increasing by 18 metres 95% CI (−18 to 56), p-value = 0.31, n = 25) over a median duration of 225 [IQR 70–311] days. Modest gains were observed in aerobic and resistance training volumes in PR with no adverse safety events. ConclusionDespite progressive and severe disease in PAH LTx candidates, patients safely participated in PR and maintained exercise capacity. Given frequent admissions, physiotherapy during hospitalization should focus on preserving functional capacity and facilitating re-integration into outpatient PR post-discharge.

Effects of Exercise Training Response on Quality of Life and Cardiovascular Risk Factor Profiles in People With Coronary Artery Disease: Insights From the HIIT or MISS UK Trial

ObjectiveTo compare the characteristics of responders and nonresponders to 8 weeks of exercise training to determine differences in key cardiovascular disease outcomes in people with coronary artery disease (CAD). DesignSecondary analysis of data from the HIIT or MISS UK trial. SettingSix outpatient National Health Service cardiac rehabilitation (CR) centers in the UK. In people with CAD attending CR, the HIIT or MISS UK trial reported that short-term, low-volume, high-intensity interval training (HIIT) was more effective than moderate-intensity steady state (MISS) exercise training for improving peak oxygen uptake (V̇o2peak). Participants382 participants with CAD (N=382) (mean age: 58.8±9.6y; mean body mass index: 29.0±4.3 kg/m2). Main Outcome MeasuresWe identified responders and nonresponders based on a meaningful change in V̇o2peak, using 2 established methods. Key clinical, quality of life (QoL), and cardiopulmonary exercise test (CPET)–derived outcomes were compared between groups. ResultsResponders were more likely to be younger (P<.05), and demonstrate greater improvement in CPET-related outcomes, for example, oxygen uptake efficiency slope, ventilatory efficiency, and peak power output (all comparisons, P<.001). Responders were more likely to observe improvements in QoL (EQ-5D-5L; mean Δ 13.6 vs mean Δ 9.4; P=.045), and high-density lipoprotein cholesterol (HDL-c) (mean Δ 0.09 mmol/L vs mean Δ 0.04 mmol/L; P=.004), compared to nonresponders. ConclusionsIn people with CAD attending CR, responders to exercise training were more likely to be younger and demonstrate greater improvements in health-related QoL and HDL-c.

Implementation and Core Components of a Multimodal Program including Exercise and Nutrition in Prevention and Treatment of Frailty in Community-Dwelling Older Adults: A Narrative Review.

Increasing disability-free life expectancy is a crucial issue to optimize active ageing and to reduce the burden of evitable medical costs. One of the main challenges is to develop pragmatic and personalized prevention strategies in order to prevent frailty, counteract adverse outcomes such as falls and mobility disability, and to improve quality of life. Strong evidence reports the effectiveness of exercise interventions to improve various physical parameters and muscle function that are cornerstones of frailty. Other findings also suggest that the interactions between nutrition and physical exercise with or without health behavior promotion prevent the development of frailty. Multimodal programs, including structured exercise, adequate dietary intervention and health behavior promotion, appear increasingly consensual. However, in order for implementation in real-life settings, some pitfalls need to be addressed. In this perspective, structuring and tailoring feasible, acceptable and sustainable interventions to optimize exercise training responses are essential conditions to warrant short, medium and long-term individual benefits. The different components of exercise programs appear to be fairly consensual and effective. However, specific composition of the programs proposed (frequency, intensity, type, time, volume and progressiveness) have to be tailored to individual characteristics and objectives in order to improve exercise responses. The intervention approaches, behavioral strategies and indications for these programs also need to be refined and framed. The main objective of this work is to guide the actions of healthcare professionals and enable them to widely and effectively implement multimodal programs including exercise, nutrition and behavioral strategies in real-life settings.

Interactions Between Statins, Exercise, and Health: A Clinical Update

Interactions Between Statins, Exercise, and Health: A Clinical Update

Canagliflozin Prevents Hyperglycemia-Associated Muscle Extracellular Matrix Accumulation and Improves the Adaptive Response to Aerobic Exercise.

Chronic hyperglycemia is associated with low response to aerobic exercise training in rodent models and humans, including reduced aerobic exercise capacity and impaired oxidative remodeling in skeletal muscle. Here, we investigated whether glucose lowering with the sodium–glucose cotransporter 2 inhibitor (SGLT2i), canagliflozin (Cana; 30 mg/kg/day), could restore exercise training response in a model of hyperglycemia (low-dose streptozotocin [STZ]). Cana effectively prevented increased blood glucose in STZ-treated mice. After 6 weeks of voluntary wheel running, Cana-treated mice displayed improvements in aerobic exercise capacity, higher capillary density in striated muscle, and a more oxidative fiber-type in skeletal muscle. In contrast, these responses were blunted or absent in STZ-treated mice. Recent work implicates glucose-induced accumulation of skeletal muscle extracellular matrix (ECM) and hyperactivation of c-Jun N-terminal kinase (JNK)/SMAD2 mechanical signaling as potential mechanisms underlying poor exercise response. In line with this, muscle ECM accretion was prevented by Cana in STZ-treated mice. JNK/SMAD2 signaling with acute exercise was twofold higher in STZ compared with control but was normalized by Cana. In human participants, ECM accumulation was associated with increased JNK signaling, low VO2peak, and impaired metabolic health (oral glucose tolerance test–derived insulin sensitivity). These data demonstrate that hyperglycemia-associated impairments in exercise adaptation can be ameliorated by cotherapy with SGLT2i.

Exercise training-induced adaptations in lung cancer patients who have undergone a lobectomy.

To determine the safety and effectiveness of a prescribed, individualized, 12-week exercise intervention on cardiorespiratory function, muscular strength, and quality of life in lung cancer patients who have undergone a lobectomy. In addition, we sought to compare the exercise training response of lung cancer patients who have undergone a lobectomy to a population of cancer patients with all other cancers in order to examine the specific effects of a lobectomy when compared to cancer patients at large. Participants were referred by a physician, and upon entry, completed an exercise-based assessment and surveys to assess various quality of life measures. Participants were divided into two groups: lung cancer patients having undergone a lobectomy (LOB, n=9) or those diagnosed with all other cancers (AOC, n=201). Participants underwent 12weeks of supervised exercise based on an individualized exercise prescription. Measures of cardiorespiratory function, muscular strength, and quality of life were collected prior to the intervention and after 12weeks of exercise training. Significant improvements to VO2peak (p<0.05) were seen in both groups. Significant improvements to muscular strength (p<0.05) were seen in both groups for all measures aside from shoulder press in the LOB group. Both groups showed significant improvements to aspects of fatigue and quality of life (p<0.05), but only the AOC group significantly improved in measures of depression (p<0.05). Exercise-based rehabilitation is a safe and effective intervention for lung cancer survivors who have undergone a lobectomy. These individuals saw significant improvements in cardiorespiratory fitness, muscular strength, and quality of life. Although there were similarities in the pattern of these training-induced improvements for these groups, lung cancer patients undergoing a lobectomy consistently demonstrated lower absolute values when compared to patients with all other cancer diagnoses.

Continuous and intermittent exercise training responses in liver and white adipose tissue aquaglyceroporins

PurposeWe analysed the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on hepatic and adipose tissue aquaglyceroporins (AQPs) in rats fed with high-fat diet (HFD).MethodsOverall, 48 male Wistar rats were fed with a normal diet (ND, 10.4 kcal% fat) or HFD (62.1 kcal% fat) over 10 weeks. Then, the animals were divided into 6 groups: ND sedentary (NS), N + MICT, N + HIIT, HS, H + MICT, and H + HIIT. The trained animals performed 10-week matched distances of MICT and HIIT on a motorized treadmill (5 times/week) while maintaining dietary treatments. The liver and epididymal white adipose tissue (eWAT) were investigated to determine triglycerides (TG) and AQP7 and AQP9 levels.ResultsHFD increased body weight, liver and eWAT weight, plasma insulin and glucose levels, and insulin resistance. Both MICT and HIIT were able to decrease body weight and liver and eWAT weight in the HFD-fed group. HFD increased plasma TG, glucose, and insulin levels, attenuated by MICT and HIIT programs. HFD increased TG content and AQP7 and did not alter AQP9. MICT and HIIT programs decreased hepatic TG content and AQP7 and AQP9 levels in ND-fed animals. In HFD-fed animals, only MICT decreased AQP9, and both MICT and HIIT decreased TG content and AQP7 levels in eWAT.ConclusionsOur findings suggest that the regulation of adipose tissue AQP7 and hepatic AQP9 by both MICT and HIIT interventions can have a significant effect on fat metabolism and glucose homeostasis.

226-OR: ADA Presidents’ Select Abstract: Exercise Training Promotes Mitochondrial Remodeling in Skeletal Muscle of Type 2 Diabetes Humans

Altered mitochondrial dynamics may contribute to impaired mitochondrial function and insulin sensitivity in type 2 diabetes (T2D). High intensity interval training (HIIT) can induce mitochondrial biogenesis in healthy humans, but its impact on mitochondrial remodeling in insulin resistant states is still unclear. To this end, this study examined the effect of HIIT on mitochondrial function and dynamics in T2D as well as in insulin resistant (IR) and sensitive (IS) glucose tolerant humans to elucidate the interplay between mitochondrial turnover and muscle insulin sensitivity. Twenty T2D, 11 IR and 12 IS humans age- and BMI-matched (HbA1c in %: 7.2 ± 0.2, 5.4 ± 0.1, 5.5 ± 0.1; M-value in mg*kg-1*min-1: 3.0 ± 0.4, 4.1 ± 0.3, 7.4 ± 0.4) performed a 12-week HIIT cycling protocol for 3 days/week. Before the intervention (baseline) and 72 h after the last exercise bout, whole-body insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps, whereas mitochondrial respiration and dynamics were assessed by high resolution respirometry and immunoblotting of skeletal muscle biopsies. After HIIT, all participants showed improved cardiorespiratory fitness and increased muscle maximal oxygen uptake (p&amp;lt;0.001 vs. baseline), whereas insulin sensitivity increased only in T2D and IR (M-value; 4.3 ± 0.5 and 5.7 ± 0.6; p&amp;lt;0.01 vs. baseline). Moreover, HIIT doubled muscle citrate synthase activity in all groups, while biomarkers of mitochondrial fission (p&amp;lt;0.01), fusion (p&amp;lt;0.001) and mitophagy (p&amp;lt;0.001 for phospho-Parkin(Ser65) and p&amp;lt;0.05 for phospho-Pink(Thr257)) increased only in T2D. In conclusion, this study suggests that mitochondrial fusion and fission synergically respond to chronic exercise training and likely contribute to the exercise training response of insulin sensitivity at least in overt T2D. Targeting these mechanisms might help to better understand muscle insulin resistance and to identify novel therapeutic strategies for tailored prevention and treatment of T2D. Disclosure L. Mastrototaro: None. M. Apostolopoulou: None. D. Pesta: None. K. Strassburger: None. Y. Karusheva: None. S. Gancheva: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Allergan plc, Bristol-Myers Squibb Company, Novo Nordisk A/S, Research Support; Self; Boehringer Ingelheim International GmbH, Danone Nutricia, Sanofi-Aventis Deutschland GmbH.

Histamine H1 and H2 receptors are essential transducers of the integrative exercise training response in humans.

Exercise training is a powerful strategy to prevent and combat cardiovascular and metabolic diseases, although the integrative nature of the training-induced adaptations is not completely understood. We show that chronic blockade of histamine H1/H2 receptors led to marked impairments of microvascular and mitochondrial adaptations to interval training in humans. Consequently, functional adaptations in exercise capacity, whole-body glycemic control, and vascular function were blunted. Furthermore, the sustained elevation of muscle perfusion after acute interval exercise was severely reduced when H1/H2 receptors were pharmaceutically blocked. Our work suggests that histamine H1/H2 receptors are important transducers of the integrative exercise training response in humans, potentially related to regulation of optimal post-exercise muscle perfusion. These findings add to our understanding of how skeletal muscle and the cardiovascular system adapt to exercise training, knowledge that will help us further unravel and develop the exercise-is-medicine concept.

Responses to exercise training in patients with heart failure. Analysis by oxygen transport steps

BackgroundExercise training (ET) increases exercise tolerance, improves quality of life and likely the prognosis in heart failure patients with reduced ejection fraction (HFrEF). However, some patients do not improve, whereas exercise training response is still poorly understood. Measurement of cardiac output during cardiopulmonary exercise test might allow ET response assessment according to the different steps of oxygen transport. MethodsFifty-three patients with HFrEF (24 with ischemic cardiomyopathy (ICM) and 29 with dilated cardiomyopathy (DCM) had an aerobic ET. Before and after ET program, peak oxygen consumption (VO2peak) and cardiac output using thoracic impedancemetry were measured. Oxygen convection (QO2peak) and diffusion (DO2) were calculated using Fick's principle and Fick's simplified law. Patients were considered as responders if the gain was superior to 10%. ResultsWe found 55% VO2peak responders, 62% QO2peak responders and 56% DO2 responders. Four patients did not have any response. None baseline predictive factor for VO2peak response was found. QO2peak response was related to exercise stroke volume (r = 0.84), cardiac power (r = 0.83) and systemic vascular resistance (SVRpeak) (r = −0.42) responses. Cardiac power response was higher in patients with ICM than in those with DCM (p < 0.05). Predictors of QO2peak response were low baseline exercise stroke volume and ICM etiology. Predictors of DO2 response were higher baseline blood creatinine and prolonged training. ConclusionThe analysis of the response to training in patients with HFrEF according to the different steps of oxygen transport revealed different phenotypes on VO2peak responses, namely responses in either oxygen convection and/or diffusion.

Women and men with coronary heart disease respond similarly to different aerobic exercise training modalities: a pooled analysis of prospective randomized trials.

We aimed to compare cardiopulmonary exercise test (CPET) parameters, cardiac adaptations, and proportion of responders after different aerobic training programs amongst women and men with coronary heart disease (CHD). Patients with CHD were evaluated with a CPET and echocardiography before and after 3 months of aerobic exercise training. Peak oxygen uptake exercise training response was assessed according to the median peak oxygen uptake change for post- versus pretraining in the whole cohort (stratification non/low responders (NLR) vs. high-responders) and normalized for lean body mass (LBM). Eighty-three CHD patients were included (19 women, 64 men; 27 patients with interval, 19 with continuous, and 37 with combination exercises). Peak oxygen uptake, peak workload normalized for LBM, pulmonary variables (i.e., ventilation and oxygen uptake efficiency slope), and O2 pulse were significantly lower in women versus men. These parameters improved similarly with training in both sexes (p < 0.05). There were no differences in the proportion of NLR among women and men with CHD (7/19 (37%) vs. 35/64 (55%), p = 0.1719). Left ventricular ejection fraction and mean peak early diastolic mitral annulus velocity improved similarly with training in both sexes (p < 0.05). Women and men with CHD have a similar exercise training response regarding key CPET and echocardiographic parameters. The proportion of responders is similar. ClinicalTrials.gov: NCT03414996, NCT02048696, NCT03443193. Novelty: Cardiopulmonary adaptations to exercise training are similar among CHD men and women. Proportion of peak oxygen uptake for non/low/high responders is similar in CHD men and women. Left ventricular systolic and diastolic function improved similarly after exercise training in CHD men and women.

Circulating and Adipose Tissue miRNAs in Women With Polycystic Ovary Syndrome and Responses to High-Intensity Interval Training.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. In women with polycystic ovary syndrome (PCOS), several miRNAs are differentially expressed compared to women without PCOS, suggesting a role for miRNAs in PCOS pathophysiology. Exercise training modulates miRNA abundance and is primary lifestyle intervention for women with PCOS. Accordingly, we measured the expression of eight circulating miRNAs selected a priori along with miRNA expression from gluteal and abdominal adipose tissue (AT) in 12 women with PCOS and 12 women matched for age and body mass index without PCOS. We also determined the miRNA expression “signatures” before and after high-intensity interval training (HIT) in 42 women with PCOS randomized to either: (1) low-volume HIT (LV-HIT, 10 × 1 min work bouts at maximal, sustainable intensity, n = 13); (2) high-volume HIT (HV-HIT, 4 × 4 min work bouts reaching 90–95% of maximal heart rate, n = 14); or (3) non-exercise control (Non-Ex, n = 15). Both HIT groups trained three times/week for 16 weeks. miRNAs were extracted from plasma, gluteal and abdominal AT, and quantified via a customized plate array containing eight miRNAs associated with PCOS and/or exercise training responses. Basal expression of circulating miRNA-27b (c-miR-27b), implicated in fatty acid metabolism, adipocyte differentiation and inflammation, was 1.8-fold higher in women with compared to without PCOS (P = 0.006) despite no difference in gluteal or abdominal AT miR-27b expression. Only the HV-HIT protocol increased peak oxygen uptake (VO2peak L/min; 9%, P = 0.008). There were no changes in body composition. In LV-HIT, but not HV-HIT, the expression of c-miR-27b decreased (0.5-fold, P = 0.007). None of the remaining seven circulating miRNAs changed in LV-HIT, nor was the expression of gluteal or abdominal AT miRNAs altered. Despite increased cardiorespiratory fitness, HV-HIT did not alter the expression of any circulating, gluteal or abdominal AT miRNAs. We conclude that women with PCOS have a higher basal expression of c-miR-27b compared to women without PCOS and that 16 weeks of LV-HIT reduces the expression of this miRNA in women with PCOS. Intense exercise training had little effect on the abundance of the selected miRNAs within subcutaneous AT depots in women with PCOS.

Nicotinamide riboside-A missing piece in the puzzle of exercise therapy for older adults?

Maintaining physical mobility is important for preventing age-related comorbidities in older adults. Endurance and resistance training prevent mobility loss in aging, but exercise alone does not always achieve the expected improvements in physical and cardiopulmonary function. Recent preclinical evidence suggests that a reason for the variability in exercise training responses may be the age-related dysregulation of the nicotinamide adenine dinucleotide (NAD+) metabolome. NAD+ is an essential enzymatic cofactor in energetic and signaling pathways. Endogenous NAD+ pool is lower in several chronic and degenerative diseases (e.g., cardiovascular diseases, Alzheimer's and Parkinson's diseases, muscular dystrophies), and also in aging. Exercise requires a higher energy expenditure than a resting state, thus a state of NAD+ insufficiency with reduced energy metabolism, could result in an inadequate exercise response. Recently, the NAD+ precursor nicotinamide riboside (NR), a vitamin B3 derivate, showed an ability to improve NAD+ metabolome homeostasis, restoring energy metabolism and cellular function in various organs in animals. NR has also been tested in older humans and is considered safe, but the effects of NR supplementation alone on physical performance are unclear. The purpose of this review is to examine the preclinical and clinical evidence on the effect of NR supplementation strategies alone and in combination with physical activity on mobility and skeletal muscle and cardiovascular function.

Effects of Age, Sex, Disease, and Exercise Training on Lip Muscle Strength

Lip muscle strength has been shown to influence daily functional activities such as facial expression, speech production, and eating. In this review, recent literature regarding lip strength and exercise training responses are summarized, highlighting the influence of sex, age, and disease (e.g., stroke). A search using five electronic databases was conducted. Twelve studies were identified from the search, which included five studies using healthy adults and seven studies using patients with diseases or chronic ailments. Regardless of the population, lip strength training multiple times a day for a relatively short term (&lt;24 weeks) has resulted in improvements of lip muscle strength. This change in lip strength has been observed in both young and old participants. Although changes in strength have been observed in both men and women, we are unaware of any studies that have tested whether there are sex differences in this response. The same directional change can be expected for patients with stroke and patients with lip incompetence, but the magnitude of the training effect seems to be higher in healthy people.

Therapist Driven Rehabilitation Protocol for Patients with Chronic Heart and Lung Diseases: A Real-Life Study.

Therapist driven protocols may help to tailor rehabilitation programs to individual patients. We aimed to test the feasibility, safety, and clinical usefulness of a therapist driven protocol for rehabilitation including exercise training of patients with heart or lung diseases. An internal audit elaborated the Cardio-Respiratory Exercise Maugeri Algorithm (CREMA) based on: (a) standardized baseline assessments, (b) decision-making pathways, and (c) frequency/intensity/time/type (FITT) of prescription for each exercise. Outpatients (n = 620) with chronic heart disease (CHD), recent myocardial revascularization (REVASC), chronic airway (Obstructive), and restrictive lung (Restrictive) diseases underwent exercise training according to CREMA during 4 years. Peripheral muscle strengthening was the most prescribed exercise (83.6%), while arm endurance training was the least frequently (0.75%). Exercise prescription varied widely among the disease groups (interval training 19–47%, balance 35–49%, lower limb muscle training 6–15%). After training, REVASC patients were the best improvers in the 6 min walking distance (+48.7 (56.1) m), maximal inspiratory pressure (+9.6 (15.4) cmH2O), and daily steps (+1087.2 (3297.1) n/day). Quadriceps and biceps strength, maximal expiratory pressure, and balance improved in all groups, without significant differences. Minor side effects were observed in 11.2% of the patients. The CREMA therapist driven protocol was feasible, safe, and useful for prescribing tailored training programs. Exercise prescriptions and training response differed among diseases.

Baseline and Exercise Predictors of V˙O2peak in Systolic Heart Failure Patients: Results from SMARTEX-HF.

This study aimed to investigate baseline, exercise testing, and exercise training-mediated predictors of change in peak oxygen uptake (V˙O2peak) from baseline to 12-wk follow-up (ΔV˙O2peak) in a post hoc analysis from the SMARTEX Heart Failure trial. We studied 215 patients with heart failure with left ventricular ejection fraction (LVEF) ≤35%, and New York Heart Association (NYHA) classes II-III who were randomized to either supervised high-intensity interval training with exercise target intensity of 90%-95% of peak heart rate (HRpeak) or supervised moderate continuous training (MCT) with target intensity of 60%-70% of HRpeak, or who received a recommendation of regular exercise on their own. Predictors of ΔV˙O2peak were assessed in two models: a logistic regression model comparing highest and lowest tertiles (baseline parameters) and a multivariate linear regression model (test/training/clinical parameters). The change in V˙O2peak in response to the interventions (ΔV˙O2peak) varied substantially, from -8.50 to +11.30 mL·kg·min. Baseline NYHA (class II gave higher odds vs III; odds ratio (OR), 7.1 (2.0-24.9); P = 0.002), LVEF (OR per percent, 1.1 (1.0-1.2); P = 0.005), and age (OR per 10 yr, 0.5 (0.3-0.8); P = 0.003) were associated with ΔV˙O2peak.In the multivariate linear regression, 34% of the variability in ΔV˙O2peak was explained by the increase in exercise training workload, ΔHRpeak between baseline and 12-wk posttesting, age, and ever having smoked. Exercise training response (ΔV˙O2peak) correlated negatively with age, LVEF, and NYHA class. The ability to increase workload during the training period and increased ΔHRpeak between baseline and the 12-wk test were associated with a positive outcome.

Contribution of Chromosome 14 to Exercise Capacity and Training Responses in Mice.

Quantitative trait loci for exercise capacity and training-induced changes in exercise capacity were identified previously on mouse Chromosome 14. The aim of this study was to further investigate the role of Chromosome 14 in exercise capacity and responses to training in mice. Exercise phenotypes were measured in chromosome substitution strain mice carrying Chromosome 14 from the PWD/PhJ donor strain on the genetic background of a host C57BL/6J (B6) strain (B6.PWD14). Eight week old female and male mice from both strains completed a graded exercise test to exhaustion to assess intrinsic or baseline exercise capacity. A separate group of 12-week old female and male mice, randomly assigned to sedentary control (SED) or exercise training (EX) groups, completed a graded exercise test before and after a 4-week exercise training period. EX mice completed a 4-week training program consisting of treadmill running 5 days/week, 60 min/day at a final intensity of approximately 65% of maximum. For intrinsic exercise capacity, exercise time and work were significantly greater in female and male B6.PWD14 than sex-matched B6 mice. In the training study, female B6.PWD14 mice had higher pre-training exercise capacity than B6 mice. In contrast, there were no significant differences for pre-training exercise capacity between male B6 and B6.PWD14 mice. There were no significant strain differences for responses to training. These data demonstrate that PWD/PhJ alleles on Chromosome 14 significantly affect intrinsic exercise capacity. Furthermore, these results support continued efforts to identify candidate genes on Chromosome 14 underlying variation in exercise capacity.

Precision exercise medicine: understanding exercise response variability

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF)...

Fitness, Function, and Exercise Training Responses after Limb Salvage With a Lower Limb Megaprosthesis: A Systematic Review.

To describe the fitness, function, and exercise training responses of patients following reconstruction of the lower limb with a total femoral (TF), proximal femoral (PF), distal femoral (DF), or proximal tibial (PT) megaprosthesis. TYPE: Systematic review. Five research databases were searched systematically for original studies published in English from 2006 to 2017 that reported fitness, functioning, or exercise training responses for one or more of the four types of lower limb megaprosthesis listed above. Methodologic quality was assessed using a 22-item modified STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. Of the 5342 articles retrieved, 28 met the inclusion criteria. Thirteen studies reported fitness outcomes, primarily in PT, with none in TF. Impaired knee extensor strength of the affected limb was reported following limb salvage with PF, DF, and PT megaprosthetics. Impaired flexibility was reported following limb salvage with DF and PT megaprosthetics. Functional outcomes were described in all studies and were most commonly reported using the Musculoskeletal Tumor Society (MSTS) system score. Results indicated no clear difference in functional outcomes between megaprosthesis locations. No studies evaluated exercise training responses. This review identified impairments of lower limb strength and flexibility following limb salvage with a lower limb megaprosthesis. Similarity in functional outcomes for all four reported megaprosthetic locations may indicate a lack of sensitivity in outcome measures, including the absence of items assessing higher-level functioning. Exercise interventions that aim to improve fitness and function in this population have not been evaluated but are required given increasing 5-year survival rates. I.

Influence of Baseline Physical Activity Level on Exercise Training Response and Clinical Outcomes in Heart Failure: The HF-ACTION Trial

ObjectivesThis study sought to evaluate the influence of baseline physical activity (PA) on responses to aerobic exercise training and clinical events in outpatients with chronic systolic heart failure (HF) from the multicenter HF-ACTION (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure) trial. BackgroundThe influence of baseline PA on exercise capacity, responses to exercise training and clinical outcomes in patients with chronic HF is unclear. MethodsOf 2,130 participants who provided consent for this analysis, 1,494 patients (64%) had complete baseline PA data, using a modified version of the International Physical Activity Questionnaire–Short Form questionnaire and were included in the analysis; 742 received usual care and 752 were allocated to the exercise training group. Changes in exercise capacity, all-cause mortality and hospitalization, cardiovascular (CV) mortality and hospitalization, and CV mortality and HF hospitalization were evaluated as a function of baseline PA tertile. ResultsAt baseline, the highest PA tertile showed greater peak oxygen uptake, cardiopulmonary exercise test duration, and 6-min walk test distance than the other 2 PA tertiles, as well as lower New York Heart Association functional class, lower Beck depression score, and lower atrial fibrillation prevalence than the lowest PA tertile. Compared to the lowest PA tertile, the middle tertile had 18% lower risk of CV death/CV hospitalizations, and the upper tertile showed 23% lower risk of CV death/HF hospitalizations. Exercise capacity and clinical outcome responses to training were similar and largely nonsignificant across baseline PA tertiles with significant benefit of training on exercise test duration for all tertiles. ConclusionsIn patients with chronic systolic HF, aerobic exercise training significantly improves exercise test duration to a similar extent across baseline PA tertiles. Although higher baseline PA was associated with lower risk of clinical events, no significant differences in event rates within each PA tertile were seen between subgroups randomized to exercise training versus usual care. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure [HF-ACTION]; NCT00047437)