Long-term effects of supervised exercise training on walking capacity and quality of life in patients with intermittent claudication

Supervised exercise training has been shown to improve walking capacity in several studies of patients with intermittent claudication. However, data on long-term outcome are quite limited. The aim of this prospective study was to evaluate long-term effects of supervised exercise training on walking capacity and quality of life in patients with intermittent claudication. Patients and methods: Sixty-seven consecutive patients with intermittent claudication who completed a supervised 12-week exercise training program were asked for follow up evaluation 39 +/- 20 months after program completion. Pain-free walking distance (PWD) and maximum walking distances (MWD) were assessed by treadmill test and several questionnaires. Results: Forty (60%) patients agreed to participate, 22 (33%) refused participation, and 5 (7%) died during follow-up. PWD and MWD significantly improved at completion of 12-weeks supervised exercise training as compared to baseline (PWD 114 +/- 100 vs. 235 +/- 248, p = 0.002; MWD 297 +/- 273 vs. 474 +/- 359, p = 0.001). Improvement of PWD and MWD could be maintained at follow up (197 +/- 254, p = 0.014; 390 +/- 324, p = 0.035, respectively) with non-smokers showing significantly better sustained PWD and MWD improvement as compared to baseline. Overall, walking capacity correlated with functional status of quality of life. Conclusions: Major findings of this investigation were that improvement in walking capacity is sustained after completion of supervised exercise training program with best results in patients who quitted or never smoked. Improved walking capacity is associated with increased functional status of quality of life.

A new standardized treadmill walking test requiring low motor skills in children aged 4-10 years

Exercise intolerance may be reported by parents of young children with respiratory diseases. There is, however, a lack of standardized exercise protocols which allow verification of these reports especially in younger children. Consequently the aims of this pilot study were to develop a standardized treadmill walking test for children aged 4-10 years demanding low sensorimotor skills and achieving high physical exhaustion. In a prospective experimental cross sectional pilot study, 33 healthy Caucasian children were separated into three groups: G1 (4-6 years, n = 10), G2 (7-8 years, n = 12), and G3 (9-10 years, n = 11). Children performed the treadmill walking test with increasing exercise levels up to peak condition with maximal exhaustion. Gas exchange, heart rate, and lactate were measured during the test, spirometry before and after. Parameters were statistically calculated at all exercise levels as well as at 2 and 4 mmol/L lactate level for group differences (Kruskal-Wallis H-test, alpha = 0.05; post hoc: Mann-Whitney U-test with Bonferroni correction alpha = 0.05/n) and test-retest differences (Wilcoxon-rank-sum test) with SPSS. The treadmill walking test could be demonstrated to be feasible with a good repeatability within groups for most of the parameters. All children achieved a high exhaustion level. At peak level under exhaustion condition only the absolute VO2 and VCO2 differed significantly between age groups. In conclusion this newly designed treadmill walking test indicates a good feasibility, safety, and repeatability. It suggests the potential usefulness of exercise capacity monitoring for children aged from early 4 to 10 years. Various applications and test modifications will be investigated in further studies.

Noninvasive measurement of cardiac output during exercise by inert gas rebreathing technique

Reduced exercise tolerance and dyspnea during exercise are hallmarks of heart failure syndrome. Exercise capacity and various parameters of cardiopulmonary response to exercise are of important prognostic value. All the available parameters only indirectly reflect left ventricular dysfunction and hemodynamic adaptation to an increased demand. Noninvasive assessment of cardiac output, especially during an incremental exercise stress test, would allow the direct measure of cardiac reserve and may become the gold standard for prognostic evaluation in the future.

The RYR2-encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome: a comprehensive open reading frame mutational analysis.

OBJECTIVES This study was undertaken to determine the spectrum and prevalence of mutations in the RYR2-encoded cardiac ryanodine receptor in cases with exertional syncope and normal corrected QT interval (QTc). BACKGROUND Mutations in RYR2 cause type 1 catecholaminergic polymorphic ventricular tachycardia (CPVT1), a cardiac channelopathy with increased propensity for lethal ventricular dysrhythmias. Most RYR2 mutational analyses target 3 canonical domains encoded by <40% of the translated exons. The extent of CPVT1-associated mutations localizing outside of these domains remains unknown as RYR2 has not been examined comprehensively in most patient cohorts. METHODS Mutational analysis of all RYR2 exons was performed using polymerase chain reaction, high-performance liquid chromatography, and deoxyribonucleic acid sequencing on 155 unrelated patients (49% females, 96% Caucasian, age at diagnosis 20 +/- 15 years, mean QTc 428 +/- 29 ms), with either clinical diagnosis of CPVT (n = 110) or an initial diagnosis of exercise-induced long QT syndrome but with QTc <480 ms and a subsequent negative long QT syndrome genetic test (n = 45). RESULTS Sixty-three (34 novel) possible CPVT1-associated mutations, absent in 400 reference alleles, were detected in 73 unrelated patients (47%). Thirteen new mutation-containing exons were identified. Two-thirds of the CPVT1-positive patients had mutations that localized to 1 of 16 exons. CONCLUSIONS Possible CPVT1 mutations in RYR2 were identified in nearly one-half of this cohort; 45 of the 105 translated exons are now known to host possible mutations. Considering that approximately 65% of CPVT1-positive cases would be discovered by selective analysis of 16 exons, a tiered targeting strategy for CPVT genetic testing should be considered.

Effects of beta-alanine supplementation and interval training on physiological determinants of severe exercise performance.

INTRODUCTION We aimed to manipulate physiological determinants of severe exercise performance. We hypothesized that (1) beta-alanine supplementation would increase intramuscular carnosine and buffering capacity and dampen acidosis during severe cycling, (2) that high-intensity interval training (HIT) would enhance aerobic energy contribution during severe cycling, and (3) that HIT preceded by beta-alanine supplementation would have greater benefits. METHODS Sixteen active men performed incremental cycling tests and 90-s severe (110 % peak power) cycling tests at three time points: before and after oral supplementation with either beta-alanine or placebo, and after an 11-days HIT block (9 sessions, 4 × 4 min), which followed supplementation. Carnosine was assessed via MR spectroscopy. Energy contribution during 90-s severe cycling was estimated from the O2 deficit. Biopsies from m. vastus lateralis were taken before and after the test. RESULTS Beta-alanine increased leg muscle carnosine (32 ± 13 %, d = 3.1). Buffering capacity and incremental cycling were unaffected, but during 90-s severe cycling, beta-alanine increased aerobic energy contribution (1.4 ± 1.3 %, d = 0.5), concurrent with reduced O2 deficit (-5.0 ± 5.0 %, d = 0.6) and muscle lactate accumulation (-23 ± 30 %, d = 0.9), while having no effect on pH. Beta-alanine also enhanced motivation and perceived state during the HIT block. There were no between-group differences in adaptations to the training block, namely increased buffering capacity (+7.9 ± 11.9 %, p = 0.04, d = 0.6, n = 14) and glycogen storage (+30 ± 47 %, p = 0.04, d = 0.5, n = 16). CONCLUSIONS Beta-alanine did not affect buffering considerably, but has beneficial effects on severe exercise metabolism as well as psychological parameters during intense training phases.

Influence of physical activity and acute exercise on cognitive performance and saliva testosterone in preadolescent school children

We investigated whether the chronic physical activity participation had an impact on the acute effects of a short bout of 12 min of intensive physical activity on cognitive performance and testosterone concentration in primary school students (n = 42, mean age = 9.69, SD = .44; experimental group (EG), n = 27; control group (CG), n = 15). Furthermore, we looked for associations between testosterone concentration and cognitive performance. After the intervention, participants of the EG showed better cognitive performances as compared to the CG. We further observed a significant group (EG, CG) test (pre, post) activity level (high, low) interaction. Post hoc pairwise comparisons revealed that after acute physical activity the testosterone concentration was diminished only in habitually low active children. The results indicate that intensive physical activity only attenuates the reactivity of the hypothalamic-pituitary-gonadal axis in habitually low active preadolescents, but had a beneficial effect on cognitive performance for all participants independent of their physical activity level and testosterone.

The effect of acute exercise and psychosocial stress on fine motor skills and testosterone concentration in the saliva of high school students

Little is known about the influence of different stressors on fine motor skills, the concentration of testosterone (T), and their interaction in adolescents. Therefore, 62 high school students aged 14–15 years were randomly assigned to two experimental groups (exercise, psychosocial stress) and a control group. Exercise stress was induced at 65–75% of the maximum heart rate by running for 15 minutes (n = 24). Psychosocial stress was generated by an intelligence test (HAWIK- IV), which was uncontrollable and characterized by social-evaluative-threat to the students (n=21). The control group followed was part of a regular school lesson with the same duration (n = 28). Saliva was collected after a normal school lesson (pre-test) as well as after the intervention/control period (post-test) and was analyzed for testosterone. Fine motor skills were assessed pre- and post-intervention using a manual dexterity test (Flower Trail) from the Movement Assessment Battery for Children-2. A repeated measure ANCOVA including gender as a covariate revealed a significant group by test interaction, indicating an increase in manual dexterity only for the psychosocial stress group. Correlation analysis of all students shows that the change of testosterone from pre- to post-test was directly linked (r = 2.31, p = .01) to the changes in manual dexterity performance. Participants showing high increases in testosterone from pre- to post-test made fewer mistakes in the fine motor skills task. Findings suggest that manual dexterity increases when psychosocial stress is induced and that improvement of manual dexterity performance corresponds with the increase of testosterone.

Peak oxygen uptake test in the assessment of growth hormone deficiency.

This study aimed at evaluating a peak oxygen uptake test as a simple diagnostic tool to assess growth-hormone deficiency (GHD) in adults. Based on the findings of multiple growth hormone (GH) samplings after the exercise, a single GH sample taken 15 min postexercise revealed high accuracy in the diagnosis of GHD in the present study. A standardized peak oxygen uptake test may, therefore, provide an accurate alternative to more invasive tests of GHD.

Exercise efficiency relates with mitochondrial content and function in older adults

Chronic aerobic exercise has been shown to increase exercise efficiency, thus allowing less energy expenditure for a similar amount of work. The extent to which skeletal muscle mitochondria play a role in this is not fully understood, particularly in an elderly population. The purpose of this study was to determine the relationship of exercise efficiency with mitochondrial content and function. We hypothesized that the greater the mitochondrial content and/or function, the greater would be the efficiencies. Thirty-eight sedentary (S, n = 23, 10F/13M) or athletic (A, n = 15, 6F/9M) older adults (66.8 ± 0.8 years) participated in this cross sectional study. V˙O2peak was measured with a cycle ergometer graded exercise protocol (GXT). Gross efficiency (GE, %) and net efficiency (NE, %) were estimated during a 1-h submaximal test (55% V˙O2peak). Delta efficiency (DE, %) was calculated from the GXT. Mitochondrial function was measured as ATPmax (mmol/L/s) during a PCr recovery protocol with (31)P-MR spectroscopy. Muscle biopsies were acquired for determination of mitochondrial volume density (MitoVd, %). Efficiencies were 17% (GE), 14% (NE), and 16% (DE) higher in A than S. MitoVD was 29% higher in A and ATPmax was 24% higher in A than in S. All efficiencies positively correlated with both ATPmax and MitoVd. Chronically trained older individuals had greater mitochondrial content and function, as well as greater exercise efficiencies. GE, NE, and DE were related to both mitochondrial content and function. This suggests a possible role of mitochondria in improving exercise efficiency in elderly athletic populations and allowing conservation of energy at moderate workloads.

Delayed positive effects of acute coordinative exercise on children’s attention

Since attention is an important prerequisite for learning, it is particularly worthwhile to promote it in schools, through specific interventions. The present study examined the effects of an acute bout of coordinative exercise in physical education on the attention of primary school children. A total of 90 fifth grade primary school children (41 boys, 49 girls; M = 11.0 yr., SD = 0.6) participated in the study and were randomly assigned to either the experimental or the control group. The experimental group received a cognitively demanding physical education lesson consisting of different coordinative exercises; the control group attended a normal sedentary school lesson. Before, immediately after, and 90 min. after each experimental condition, the children's attentional performance was tested using the revised version of the d2 Test of Attention (d2-R). Results of the repeated-measures analysis of variance (ANOVA) revealed that children's attentional performance increased through the specifically designed physical education lesson, not immediately but 90 min. after cessation. The results are discussed in terms of mechanisms explaining the relationship between acute physical exercise, and immediate and delayed effects on attention.

Integrated mRNA and miRNA expression profiling in blood reveals candidate biomarkers associated with endurance exercise in the horse.

The adaptive response to extreme endurance exercise might involve transcriptional and translational regulation by microRNAs (miRNAs). Therefore, the objective of the present study was to perform an integrated analysis of the blood transcriptome and miRNome (using microarrays) in the horse before and after a 160 km endurance competition. A total of 2,453 differentially expressed genes and 167 differentially expressed microRNAs were identified when comparing pre- and post-ride samples. We used a hypergeometric test and its generalization to gain a better understanding of the biological functions regulated by the differentially expressed microRNA. In particular, 44 differentially expressed microRNAs putatively regulated a total of 351 depleted differentially expressed genes involved variously in glucose metabolism, fatty acid oxidation, mitochondrion biogenesis, and immune response pathways. In an independent validation set of animals, graphical Gaussian models confirmed that miR-21-5p, miR-181b-5p and miR-505-5p are candidate regulatory molecules for the adaptation to endurance exercise in the horse. To the best of our knowledge, the present study is the first to provide a comprehensive, integrated overview of the microRNA-mRNA co-regulation networks that may have a key role in controlling post-transcriptomic regulation during endurance exercise.

Cognitively engaging chronic physical activity, but not aerobic exercise, affects executive functions in primary school children: A group-randomized controlled trial

Although the positive effects of different kinds of physical activity (PA) on cognitive functioning have already been demonstrated in a variety of studies, the role of cognitive engagement in promoting children’s executive functions is still unclear. The aim of the present study was therefore to investigate the effects of two qualitatively different chronic PA interventions on executive functions in primary school children. 181 children aged between 10 and 12 years were assigned to either a 6-week physical education program with a high level of physical exertion and high cognitive engagement (team games), a physical education program with high physical exertion but low cognitive engagement (aerobic exercise), or to a physical education program with both low physical exertion and low cognitive engagement (control condition). Executive functions (updating, inhibition, shifting) and aerobic fitness (multistage 20-meter shuttle run test) were measured before and after the respective condition. Results revealed that both interventions (team games and aerobic exercise) have a positive impact on children’s aerobic fitness (4-5 % increase in estimated VO2max). Importantly, an improvement in shifting performance was found only in the team games and not in the aerobic exercise or control condition. Thus, the inclusion of cognitive engagement in PA seems to be the most promising type of chronic intervention to enhance executive functions in children, providing further evidence for the importance of the qualitative aspects of PA.

Investigation of robotics-assisted tilt table technology for cardiopulmonary exercise testing in stroke patients

Due to the lack of exercise testing devices that can be employed in stroke patients with severe disability, the aim of this PhD research was to investigate the clinical feasibility of using a robotics-assisted tilt table (RATT) as a method for cardiopulmonary exercise testing (CPET) and exercise training in stroke patients. For this purpose, the RATT was augmented with force sensors, a visual feedback system and a work rate calculation algorithm. As the RATT had not been used previously for CPET, the first phase of this project focused on a feasibility study in 11 healthy able-bodied subjects. The results demonstrated substantial cardiopulmonary responses, no complications were found, and the method was deemed feasible. The second phase was to analyse validity and test-retest reliability of the primary CPET parameters obtained from the RATT in 18 healthy able-bodied subjects and to compare the outcomes to those obtained from standard exercise testing devices (a cycle ergometer and a treadmill). The results demonstrated that peak oxygen uptake (V'O2peak) and oxygen uptake at the submaximal exercise thresholds on the RATT were ̴20% lower than for the cycle ergometer and ̴30% lower than on the treadmill. A very high correlation was found between the RATT vs the cycle ergometer V'O2peak and the RATT vs the treadmill V'O2peak. Test-retest reliability of CPET parameters obtained from the RATT were similarly high to those for standard exercise testing devices. These findings suggested that the RATT is a valid and reliable device for CPET and that it has potential to be used in severely impaired patients. Thus, the third phase was to investigate using the RATT for CPET and exercise training in 8 severely disabled stroke patients. The method was technically implementable, well tolerated by the patients, and substantial cardiopulmonary responses were observed. Additionally, all patients could exercise at the recommended training intensity for 10 min bouts. Finally, an investigation of test-retest reliability and four-week changes in cardiopulmonary fitness was carried out in 17 stroke patients with various degrees of disability. Good to excellent test-retest reliability and repeatability were found for the main CPET variables. There was no significant difference in most CPET parameters over four weeks. In conclusion, based on the demonstrated validity, reliability and repeatability, the RATT was found to be a feasible and appropriate alternative exercise testing and training device for patients who have limitations for use of standard devices.

Regulation of fuel metabolism during exercise in hypopituitarism with growth hormone-deficiency (GHD).

OBJECTIVE Growth hormone (GH) has a strong lipolytic action and its secretion is increased during exercise. Data on fuel metabolism and its hormonal regulation during prolonged exercise in patients with growth hormone deficiency (GHD) is scarce. This study aimed at evaluating the hormonal and metabolic response during aerobic exercise in GHD patients. DESIGN Ten patients with confirmed GHD and 10 healthy control individuals (CI) matched for age, sex, BMI, and waist performed a spiroergometric test to determine exercise capacity (VO2max). Throughout a subsequent 120-minute exercise on an ergometer at 50% of individual VO2max free fatty acids (FFA), glucose, GH, cortisol, catecholamines and insulin were measured. Additionally substrate oxidation assessed by indirect calorimetry was determined at begin and end of exercise. RESULTS Exercise capacity was lower in GHD compared to CI (VO2max 35.5±7.4 vs 41.5±5.5ml/min∗kg, p=0.05). GH area under the curve (AUC-GH), peak-GH and peak-FFA were lower in GHD patients during exercise compared to CI (AUC-GH 100±93.2 vs 908.6±623.7ng∗min/ml, p<0.001; peak-GH 1.5±1.53 vs 12.57±9.36ng/ml, p<0.001, peak-FFA 1.01±0.43 vs 1.51±0.56mmol/l, p=0.036, respectively). There were no significant differences for insulin, cortisol, catecholamines and glucose. Fat oxidation at the end of exercise was higher in CI compared to GHD patients (295.7±73.9 vs 187.82±103.8kcal/h, p=0.025). CONCLUSION A reduced availability of FFA during a 2-hour aerobic exercise and a reduced fat oxidation at the end of exercise may contribute to the decreased exercise capacity in GHD patients. Catecholamines and cortisol do not compensate for the lack of the lipolytic action of GH in patients with GHD.

Methodological and physiological test-retest reliability of (13) C-MRS glycogen measurements in liver and in skeletal muscle of patients with type 1 diabetes and matched healthy controls.

Glycogen is a major substrate in energy metabolism and particularly important to prevent hypoglycemia in pathologies of glucose homeostasis such as type 1 diabetes mellitus (T1DM). (13) C-MRS is increasingly used to determine glycogen in skeletal muscle and liver non-invasively; however, the low signal-to-noise ratio leads to long acquisition times, particularly when glycogen levels are determined before and after interventions. In order to ease the requirements for the subjects and to avoid systematic effects of the lengthy examination, we evaluated if a standardized preparation period would allow us to shift the baseline (pre-intervention) experiments to a preceding day. Based on natural abundance (13) C-MRS on a clinical 3 T MR system the present study investigated the test-retest reliability of glycogen measurements in patients with T1DM and matched controls (n = 10 each group) in quadriceps muscle and liver. Prior to the MR examination, participants followed a standardized diet and avoided strenuous exercise for two days. The average coefficient of variation (CV) of myocellular glycogen levels was 9.7% in patients with T1DM compared with 6.6% in controls after a 2 week period, while hepatic glycogen variability was 13.3% in patients with T1DM and 14.6% in controls. For comparison, a single-session test-retest variability in four healthy volunteers resulted in 9.5% for skeletal muscle and 14.3% for liver. Glycogen levels in muscle and liver were not statistically different between test and retest, except for hepatic glycogen, which decreased in T1DM patients in the retest examination, but without an increase of the group distribution. Since the CVs of glycogen levels determined in a "single session" versus "within weeks" are comparable, we conclude that the major source of uncertainty is the methodological error and that physiological variations can be minimized by a pre-study standardization. For hepatic glycogen examinations, familiarization sessions (MR and potentially strenuous interventions) are recommended. Copyright © 2016 John Wiley & Sons, Ltd.