Reduced exercise tolerance in CHF may be related to factors other than impaired skeletal muscle oxidative capacity

Background : We sought to determine whether skeletal muscle oxidative capacity, fiber type proportions, and fiber size, capillary density or muscle mass might explain the impaired exercise tolerance in chronic heart failure (CHF). Previous studies are equivocal regarding the maladaptations that occur in the skeletal muscle of patients with CHF and their role in the observed exercise intolerance.

Methods and results : Total body O₂ uptake (VO_2peak) was determined in 14 CHF patients and 8 healthy sedentary similar-age controls. Muscle samples were analyzed for mitochondrial adenosine triphosphate (ATP) production rate (MAPR), oxidative and glycolytic enzyme activity, fiber size and type, and capillary density. CHF patients demonstrated a lower VO_2peak (15.1±1.1 versus 28.1±2.3 mL·kg⁻¹·min⁻¹, P<.001) and capillary to fiber ratio (1.09±0.05 versus 1.40±0.04; P<.001) when compared with controls. However, there was no difference in capillary density (capillaries per square millimeter) across any of the fiber types. Measurements of MAPR and oxidative enzyme activity suggested no difference in muscle oxidative capacity between the groups.

Conclusions : Neither reductions in muscle oxidative capacity nor capillary density appear to be the cause of exercise limitation in this cohort of patients. Therefore, we hypothesize that the low VO_2peak observed in CHF patients may be the result of fiber atrophy and possibly impaired activation of oxidative phosphorylation.

Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation

The ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription factor Kruppel-like factor 15 (KLF15) is an important regulator of glucose and amino acid metabolism, its endogenous role in lipid homeostasis and muscle physiology is unknown. Here we demonstrate that KLF15 is essential for skeletal muscle lipid utilization and physiologic performance. KLF15 directly regulates a broad transcriptional program spanning all major segments of the lipid-flux pathway in muscle. Consequently, Klf15-deficient mice have abnormal lipid and energy flux, excessive reliance on carbohydrate fuels, exaggerated muscle fatigue, and impaired endurance exercise capacity. Elucidation of this heretofore unrecognized role for KLF15 now implicates this factor as a central component of the transcriptional circuitry that coordinates physiologic flux of all three basic cellular nutrients: glucose, amino acids, and lipids.

Exercise during hemodialysis : the intradialytic zumba gold

People requiring dialysis have a lower exercise capacity than the non-ESRD population. Lower exercise capacity is associated with deconditioning, which leads to a reduced quality of life and increased risk of injury. Low-impact exercise programs during dialysis have been found to be safe and beneficial for this group. In addition, intradialytic exercise can alleviate the boredom of receiving dialysis, creating an exercise-focused positive environment in the dialysis center. Increased physical activity may influence people's physical function and confidence, which may further encourage patient empowerment.

MicroRNA-23a has minimal effect on endurance exercise-induced adaptation of mouse skeletal muscle.

Skeletal muscles contain several subtypes of myofibers that differ in contractile and metabolic properties. Transcriptional control of fiber-type specification and adaptation has been intensively investigated over the past several decades. Recently, microRNA (miRNA)-mediated posttranscriptional gene regulation has attracted increasing attention. MiR-23a targets key molecules regulating contractile and metabolic properties of skeletal muscle, such as myosin heavy-chains and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α). In the present study, we analyzed the skeletal muscle phenotype of miR-23a transgenic (miR-23a Tg) mice to explore whether forced expression of miR-23a affects markers of mitochondrial content, muscle fiber composition, and muscle adaptations induced by 4 weeks of voluntary wheel running. When compared with wild-type mice, protein markers of mitochondrial content, including PGC-1α, and cytochrome c oxidase complex IV (COX IV), were significantly decreased in the slow soleus muscle, but not the fast plantaris muscle of miR-23a Tg mice. There was a decrease in type IId/x fibers only in the soleus muscle of the Tg mice. Following 4 weeks of voluntary wheel running, there was no difference in the endurance exercise capacity as well as in several muscle adaptive responses including an increase in muscle mass, capillary density, or the protein content of myosin heavy-chain IIa, PGC-1α, COX IV, and cytochrome c. These results show that miR-23a targets PGC-1α and regulates basal metabolic properties of slow but not fast twitch muscles. Elevated levels of miR-23a did not impact on whole body endurance capacity or exercise-induced muscle adaptations in the fast plantaris muscle.

MicroRNA-23a has minimal effect on endurance exercise-induced adaptation of mouse skeletal muscle

Skeletal muscles contain several subtypes of myofibers that differ in contractile and metabolic properties. Transcriptional control of fiber-type specification and adaptation has been intensively investigated over the past several decades. Recently, microRNA (miRNA)-mediated posttranscriptional gene regulation has attracted increasing attention. MiR-23a targets key molecules regulating contractile and metabolic properties of skeletal muscle, such as myosin heavy-chains and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α). In the present study, we analyzed the skeletal muscle phenotype of miR-23a transgenic (miR-23a Tg) mice to explore whether forced expression of miR-23a affects markers of mitochondrial content, muscle fiber composition, and muscle adaptations induced by 4 weeks of voluntary wheel running. When compared with wild-type mice, protein markers of mitochondrial content, including PGC-1α, and cytochrome c oxidase complex IV (COX IV), were significantly decreased in the slow soleus muscle, but not the fast plantaris muscle of miR-23a Tg mice. There was a decrease in type IId/x fibers only in the soleus muscle of the Tg mice. Following 4 weeks of voluntary wheel running, there was no difference in the endurance exercise capacity as well as in several muscle adaptive responses including an increase in muscle mass, capillary density, or the protein content of myosin heavy-chain IIa, PGC-1α, COX IV, and cytochrome c. These results show that miR-23a targets PGC-1α and regulates basal metabolic properties of slow but not fast twitch muscles. Elevated levels of miR-23a did not impact on whole body endurance capacity or exercise-induced muscle adaptations in the fast plantaris muscle.

Telehealth exercise-based cardiac rehabilitation: a systematic review and meta-analysis

OBJECTIVE: Despite proven effectiveness, participation in traditional supervised exercise-based cardiac rehabilitation (exCR) remains low. Telehealth interventions that use information and communication technologies to enable remote exCR programme delivery can overcome common access barriers while preserving clinical supervision and individualised exercise prescription. This meta-analysis aimed to determine the benefits of telehealth exCR on exercise capacity and other modifiable cardiovascular risk factors compared with traditional exCR and usual care, among patients with coronary heart disease (CHD). METHODS: CINAHL, The Cochrane Library, Embase, MEDLINE, PubMed and PsycINFO were searched from inception through 31 May 2015 for randomised controlled trials comparing telehealth exCR with centre-based exCR or usual care among patients with CHD. Outcomes included maximal aerobic exercise capacity, modifiable cardiovascular risk factors and exercise adherence. RESULTS: 11 trials (n=1189) met eligibility criteria and were included in the review. Physical activity level was higher following telehealth exCR than after usual care. Compared with centre-based exCR, telehealth exCR was more effective for enhancing physical activity level, exercise adherence, diastolic blood pressure and low-density lipoprotein cholesterol. Telehealth and centre-based exCR were comparably effective for improving maximal aerobic exercise capacity and other modifiable cardiovascular risk factors. CONCLUSIONS: Telehealth exCR appears to be at least as effective as centre-based exCR for improving modifiable cardiovascular risk factors and functional capacity, and could enhance exCR utilisation by providing additional options for patients who cannot attend centre-based exCR. Telehealth exCR must now capitalise on technological advances to provide more comprehensive, responsive and interactive interventions.

Voluntary running aids to maintain high body temperature in rats bred for high aerobic capacity

The production of heat, i.e., thermogenesis, is a significant component of the metabolic rate, which in turn affects weight gain and health. Thermogenesis is linked to physical activity (PA) level. However, it is not known whether intrinsic exercise capacity, aging, and long-term voluntary running affect core body temperature. Here we use rat models selectively bred to differ in maximal treadmill endurance running capacity (Low capacity runners, LCR and High capacity Runners, HCR), that as adults are divergent for aerobic exercise capacity, aging, and metabolic disease risk to study the connection between PA and body temperature. Ten high capacity runner (HCR) and ten low capacity runner (LCR) female rats were studied between 9 and 21 months of age. Rectal body temperature of HCR and LCR rats was measured before and after 1-year voluntary running/control intervention to explore the effects of aging and PA. Also, we determined whether injected glucose and spontaneous activity affect the body temperature differently between LCR and HCR rats at 9 vs. 21 months of age. HCRs had on average 1.3°C higher body temperature than LCRs (p < 0.001). Aging decreased the body temperature level of HCRs to similar levels with LCRs. The opportunity to run voluntarily had a significant impact on the body temperature of HCRs (p < 0.001) allowing them to maintain body temperature at a similar level as when at younger age. Compared to LCRs, HCRs were spontaneously more active, had higher relative gastrocnemius muscle mass and higher UCP2, PGC-1α, cyt c, and OXPHOS levels in the skeletal muscle (p < 0.050). These results suggest that higher PA level together with greater relative muscle mass and higher mitochondrial content/function contribute to the accumulation of heat in the HCRs. Interestingly, neither aging nor voluntary training had a significant impact on core body temperature of LCRs. However, glucose injection resulted in a lowering of the body temperature of LCRs (p < 0.050), but not that of HCRs. In conclusion, rats born with high intrinsic capacity for aerobic exercise and better health have higher body temperature compared to rats born with low exercise capacity and disease risk. Voluntary running allowed HCRs to maintain high body temperature during aging, which suggests that high PA level was crucial in maintaining the high body temperature of HCRs.

HEART: heart exercise and remote technologies: a randomized controlled trial study protocol.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) is aimed at improving health behaviors to slow or reverse the progression of CVD disease. Exercise is a central element of CR. Technologies such as mobile phones and the Internet (mHealth) offer potential to overcome many of the psychological, physical, and geographical barriers that have been associated with lack of participation in exercise-based CR. We aim to trial the effectiveness of a mobile phone delivered exercise-based CR program to increase exercise capacity and functional outcomes compared with usual CR care in adults with CVD. This paper outlines the rationale and methods of the trial.

METHODS: A single-blinded parallel two-arm randomized controlled trial is being conducted. A total of 170 people will be randomized at 1:1 ratio either to receive a mHealth CR program or usual care. Participants are identified by CR nurses from two metropolitan hospitals in Auckland, New Zealand through outpatient clinics and existing databases. Consenting participants are contacted to attend a baseline assessment. The intervention consists of a theory-based, personalized, automated package of text and video message components via participants' mobile phones and the Internet to increase exercise behavior, delivered over six months. The control group will continue with usual CR. Data collection occurs at baseline and 24 weeks (post-intervention). The primary outcome is change in maximal oxygen uptake from baseline to 24 weeks. Secondary outcomes include post-intervention measures on self-reported physical activity (IPAQ), cardiovascular risk factors (systolic blood pressure, weight, and waist to hip ratio), health related quality of life (SF-36), and cost-effectiveness.

DISCUSSION: This manuscript presents the protocol for a randomized controlled trial of a mHealth exercise-based CR program. Results of this trial will provide much needed information about physical and psychological well-being, and cost-effectiveness of an automated telecommunication intervention. If effective, this intervention has enormous potential to improve the delivery of CR and could easily be scaled up to be delivered nationally (and internationally) in a very short time, enhancing the translational aspect of this research. It also has potential to extend to comprehensive CR (nutrition advice, smoking cessation, medication adherence).

A mobile phone intervention increases physical activity in people with cardiovascular disease: Results from the HEART randomized controlled trial.

AIM: To determine the effectiveness and cost-effectiveness of a mobile phone intervention to improve exercise capacity and physical activity behaviour in people with ischaemic heart disease (IHD).

METHODS AND RESULTS: In this single-blind, parallel, two-arm, randomized controlled trial adults (n = 171) with IHD were randomized to receive a mobile phone delivered intervention (HEART; n = 85) plus usual care, or usual care alone (n = 86). Adult participants aged 18 years or more, with a diagnosis of IHD, were clinically stable as outpatients, able to perform exercise, able to understand and write English, and had access to the Internet. The HEART (Heart Exercise And Remote Technologies) intervention involved a personalized, automated package of text messages and a secure website with video messages aimed at increasing exercise behaviour, delivered over 24 weeks. All participants were able to access usual community-based cardiac rehabilitation, which involves encouragement of physical activity and an offer to join a local cardiac support club. All outcomes were assessed at baseline and 24 weeks and included peak oxygen uptake (PVO2; primary outcome), self-reported physical activity, health-related quality of life, self-efficacy and motivation (secondary outcomes). Results showed no differences in PVO2 between the two groups (difference -0.21 ml kg(-1)min(-1), 95% CI: -1.1, 0.7; p = 0.65) at 24 weeks. However significant treatment effects were observed for selected secondary outcomes, including leisure time physical activity (difference 110.2 min/week, 95% CI: -0.8, 221.3; p = 0.05) and walking (difference 151.4 min/week, 95% CI: 27.6, 275.2; p = 0.02). There were also significant improvements in self-efficacy to be active (difference 6.2%, 95% CI: 0.2, 12.2; p = 0.04) and the general health domain of the SF36 (difference 2.1, 95% CI: 0.1, 4.1; p = 0.03) at 24 weeks. The HEART programme was considered likely to be cost-effective for leisure time activity and walking.

CONCLUSIONS: A mobile phone intervention was not effective at increasing exercise capacity over and above usual care. The intervention was effective and probably cost-effective for increasing physical activity and may have the potential to augment existing cardiac rehabilitation services.

The HEART mobile phone trial: the partial mediating effects of self-efficacy on physical activity among cardiac patients

BACKGROUND: The ubiquitous use of mobile phones provides an ideal opportunity to deliver interventions to increase physical activity levels. Understanding potential mediators of such interventions is needed to increase their effectiveness. A recent randomized controlled trial of a mobile phone and Internet (mHealth) intervention was conducted in New Zealand to determine the effectiveness on exercise capacity and physical activity levels in addition to current cardiac rehabilitation (CR) services for people (n = 171) with ischemic heart disease. Significant intervention effect was observed for self-reported leisure-time physical activity and walking, but not peak oxygen uptake at 24 weeks. There was also significant improvement in self-efficacy.

OBJECTIVE: To evaluate the mediating effect of self-efficacy on physical activity levels in an mHealth delivered exercise CR program.

METHODS: Treatment evaluations were performed on the principle of intention to treat. Adjusted regression analyses were conducted to evaluate the main treatment effect on leisure-time physical activity and walking at 24 weeks, with and without change in self-efficacy as the mediator of interest.

RESULTS: Change in self-efficacy at 24 weeks significantly mediated the treatment effect on leisure-time physical activity by 13%, but only partially mediated the effect on walking by 4% at 24 weeks.

CONCLUSION: An mHealth intervention involving text messaging and Internet support had a positive treatment effect on leisure-time physical activity and walking at 24 weeks, and this effect was likely mediated through changes in self-efficacy. Future trials should examine other potential mediators related to this type of intervention.

Disruption of the class IIa HDAC corepressor complex increases energy expenditure and lipid oxidation

Drugs that recapitulate aspects of the exercise adaptive response have the potential to provide better treatment for diseases associated with physical inactivity. We previously observed reduced skeletal muscle class IIa HDAC (histone deacetylase) transcriptional repressive activity during exercise. Here, we find that exercise-like adaptations are induced by skeletal muscle expression of class IIa HDAC mutants that cannot form a corepressor complex. Adaptations include increased metabolic gene expression, mitochondrial capacity, and lipid oxidation. An existing HDAC inhibitor, Scriptaid, had similar phenotypic effects through disruption of the class IIa HDAC corepressor complex. Acute Scriptaid administration to mice increased the expression of metabolic genes, which required an intact class IIa HDAC corepressor complex. Chronic Scriptaid administration increased exercise capacity, whole-body energy expenditure and lipid oxidation, and reduced fasting blood lipids and glucose. Therefore, compounds that disrupt class IIa HDAC function could be used to enhance metabolic health in chronic diseases driven by physical inactivity.

The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding capacity in human skeletal muscle

AS160 is an Akt substrate of 160 kDa implicated in the regulation of both insulin- and contraction-mediated GLUT4 translocation and glucose uptake. The effects of aerobic exercise and subsequent insulin stimulation on AS160 phosphorylation and the binding capacity of 14-3-3, a novel protein involved in the dissociation of AS160 from GLUT4 vesicles, in human skeletal muscle are unknown. Hyperinsulinemic-euglycemic clamps were performed on seven men at rest and immediately and 3 h after a single bout of cycling exercise. Skeletal muscle biopsies were taken before and after the clamps. The insulin sensitivity index calculated during the final 30 min of the clamp was 8.0 ± 0.8, 9.1 ± 0.5, and 9.2 ± 0.8 for the rest, postexercise, and 3-h postexercise trials, respectively. AS160 phosphorylation increased immediately after exercise and remained elevated 3 h after exercise. In contrast, the 14-3-3 binding capacity of AS160 and phosphorylation of Akt and AMP-activated protein kinase were only increased immediately after exercise. Insulin increased AS160 phosphorylation and 14-3-3 binding capacity and insulin receptor substrate-1 and Akt phosphorylation, but the response to insulin was not enhanced by prior exercise. In conclusion, the 14-3-3 binding capacity of AS160 is increased immediately after acute exercise in human skeletal muscle, but this is not maintained 3 h after exercise completion despite sustained AS160 phosphorylation. Insulin increases AS160 phosphorylation and 14-3-3 binding capacity, but prior exercise does not appear to enhance the response to insulin.