Tanya M. Holloway

One Week of Bed Rest Leads to Substantial Muscle Atrophy and Induces Whole-Body Insulin Resistance in the Absence of Skeletal Muscle Lipid Accumulation

Short (<10 days) periods of muscle disuse, often necessary for recovery from illness or injury, lead to various negative health consequences. The current study investigated mechanisms underlying disuse-induced insulin resistance, taking into account muscle atrophy. Ten healthy, young males (age: 23 ± 1 years; BMI: 23.0 ± 0.9 kg · m−2) were subjected to 1 week of strict bed rest. Prior to and after bed rest, lean body mass (dual-energy X-ray absorptiometry) and quadriceps cross-sectional area (CSA; computed tomography) were assessed, and peak oxygen uptake (VO2peak) and leg strength were determined. Whole-body insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Additionally, muscle biopsies were collected to assess muscle lipid (fraction) content and various markers of mitochondrial and vascular content. Bed rest resulted in 1.4 ± 0.2 kg lean tissue loss and a 3.2 ± 0.9% decline in quadriceps CSA (both P < 0.01). VO2peak and one-repetition maximum declined by 6.4 ± 2.3 (P < 0.05) and 6.9 ± 1.4% (P < 0.01), respectively. Bed rest induced a 29 ± 5% decrease in whole-body insulin sensitivity (P < 0.01). This was accompanied by a decline in muscle oxidative capacity, without alterations in skeletal muscle lipid content or saturation level, markers of oxidative stress, or capillary density. In conclusion, 1 week of bed rest substantially reduces skeletal muscle mass and lowers whole-body insulin sensitivity, without affecting mechanisms implicated in high-fat diet–induced insulin resistance.

Cardiac Rehabilitation Wait Times: EFFECT ON ENROLLMENT

PURPOSE: Cardiac rehabilitation (CR) is a proven effective means for secondary prevention of coronary heart disease. Timely access to CR services is key to promoting patient participation and ensuring optimal patient outcomes. Despite wait time benchmarks having been established, research regarding how long patients wait to enter CR following referral receipt is limited. The aim of this study was to (a) describe wait times from CR referral to intake assessment and (b) examine the association of wait time to CR enrollment rates. METHODS: Wait time from date of CR referral to date of intake assessment was calculated in days for 599 participants referred to CR from 2006 to 2009 inclusive. A descriptive examination of sociodemographic and clinical characteristics was performed, followed by logistic regression analysis to assess the wait time by enrollment relationship. RESULTS: Median wait time from referral receipt to CR intake was 42.0 days. Wait time had a negative effect on CR enrollment, such that for every 1-day increment in wait time, patients were 1% less likely to enroll. CONCLUSIONS: The time that patients wait to enroll in CR may affect the number of patients who choose to attend, and longer wait times may mean fewer patients will benefit from CR participation. Programs should be encouraged to undertake quality improvement initiatives to ensure wait times are not negatively impacting patient enrollment and ultimately preventing patients from benefiting from CR participation. Further research is needed to establish evidence-based wait time benchmarks and interventions to promote timely access to CR services.

High Intensity Interval and Endurance Training Have Opposing Effects on Markers of Heart Failure and Cardiac Remodeling in Hypertensive Rats

There has been re-emerging interest and significant work dedicated to investigating the metabolic effects of high intensity interval training (HIIT) in recent years. HIIT is considered to be a time efficient alternative to classic endurance training (ET) that elicits similar metabolic responses in skeletal muscle. However, there is a lack of information on the impact of HIIT on cardiac muscle in disease. Therefore, we determined the efficacy of ET and HIIT to alter cardiac muscle characteristics involved in the development of diastolic dysfunction, such as ventricular hypertrophy, fibrosis and angiogenesis, in a well-established rodent model of hypertension-induced heart failure before the development of overt heart failure. ET decreased left ventricle fibrosis by ~40% (P < 0.05), and promoted a 20% (P<0.05) increase in the left ventricular capillary/fibre ratio, an increase in endothelial nitric oxide synthase protein (P<0.05), and a decrease in hypoxia inducible factor 1 alpha protein content (P<0.05). In contrast, HIIT did not decrease existing fibrosis, and HIIT animals displayed a 20% increase in left ventricular mass (P<0.05) and a 20% decrease in cross sectional area (P<0.05). HIIT also increased brain natriuretic peptide by 50% (P<0.05), in the absence of concomitant angiogenesis, strongly suggesting pathological cardiac remodeling. The current data support the longstanding belief in the effectiveness of ET in hypertension. However, HIIT promoted a pathological adaptation in the left ventricle in the presence of hypertension, highlighting the need for further research on the widespread effects of HIIT in the presence of disease.

CrossTalk opposing view: High intensity interval training does not have a role in risk reduction or treatment of disease.

Moderate-intensity continuous exercise has been used in clinical settings for decades and is known to have a plethora of benefits. The beneficial effects of endurance exercise are well documented: exercise adaptations result in mitochondrial biogenesis, increased skeletal muscle capillarization, improved vascular compliance, and increased stroke volume and cardiac output (Holloszy, 1973; Clausen, 1977). As a result, chronic endurance training (ET) is a well-known primary and secondary prevention tool for various pathologies, including, but not limited to, diabetes mellitus (Boule et al. 2001), hypertension (Cornelissen & Smart, 2013) and heart failure (HF) (Pina et al. 2003). Given the well-documented benefits of exercise on health, and the increasing incidence of lifestyle-related diseases, there is renewed interest in identifying the optimal exercise prescription. Two broad types of aerobic training have largely been represented in the literature: ET ( 50–80% V̇O2max) and higher-intensity/explosive type training. The latter is further delineated as either sprint interval training (SIT; short bursts at > 100% V̇O2max) or high-intensity interval training (HIIT; 90% V̇O2max),

Resistance Training Increases Skeletal Muscle Capillarization in Healthy Older Men

PURPOSE Skeletal muscle capillarization plays a key role in oxygen and nutrient delivery to muscle. The loss of muscle mass with aging and the concept of anabolic resistance have been, at least partly, attributed to changes in skeletal muscle capillary structure and function. We aimed to compare skeletal muscle capillarization between young and older men and evaluate whether resistance-type exercise training increases muscle capillarization in older men. METHODS Muscle biopsies were obtained from the vastus lateralis of healthy young (n = 14, 26 ± 2 yr) and older (n = 16, 72 ± 1 yr) adult men, with biopsies before and after 12 wk of resistance-type exercise training in the older subjects. Immunohistochemistry was used to assess skeletal muscle fiber size, capillary contacts (CC) per muscle fiber, and the capillary-to-fiber perimeter exchange (CFPE) index in type I and II muscle fibers. RESULTS Type II muscle fibers were smaller in old versus young (4507 ± 268 vs 6084 ± 497 μm, respectively, P = 0.007). Type I and type II muscle fiber CC and CFPE index were smaller in old compared with young muscle (CC type I: 3.8 ± 0.2 vs 5.0 ± 0.3; CC type II: 3.2 ± 0.2 vs 4.2 ± 0.2, respectively; both P < 0.001). Resistance-type exercise training increased type II muscle fiber size only. In addition, CC and CFPE index increased in both the type I (26% ± 9% and 27% ± 8%) and type II muscle fibers (33% ± 7% and 24% ± 6%, respectively; all P ≤ 0.001) after 12 wk resistance training in older men. CONCLUSIONS We conclude that resistance-type exercise training can effectively augment skeletal muscle fiber capillarization in older men. The greater capillary supply may be an important prerequisite to reverse anabolic resistance and support muscle hypertrophy during lifestyle interventions aiming to support healthy aging.

High intensity interval and endurance training are associated with divergent skeletal muscle adaptations in a rodent model of hypertension

Skeletal muscle is extremely adaptable to a variety of metabolic challenges, as both traditional moderate-intensity endurance (ET) and high-intensity interval training (HIIT) increases oxidative potential in a coordinated manner. Although these responses have been clearly demonstrated in healthy individuals, it remains to be determined whether both produce similar responses in the context of hypertension, one of the most prevalent and costly diseases worldwide. Therefore, in the current study, we used the Dahl sodium-sensitive rat, a model of hypertension, to determine the molecular responses to 4 wk of either ET or HIIT in the red (RG) and white gastrocnemius (WG) muscles. In the RG, both ET and HIIT increased the content of electron transport chain proteins and increased succinate dehydrogenase (SDH) content in type I fibers. Although both intensities of exercise shifted fiber type in RG (increased IIA, decreased IIX), only HIIT was associated with a reduction in endothelial nitric oxide synthase and an increase in HIF-1α proteins. In the WG, both ET and HIIT increased markers of the electron transport chain; however, HIIT decreased SDH content in a fiber-specific manner. ET increased type IIA, decreased IIB fibers, and increased capillarization, while, in contrast, HIIT increased the percentage of IIB fibers, decreased capillary-to-fiber ratios, decreased endothelial nitric oxide synthase, and increased hypoxia inducible factor-1α (HIF-1α) protein. Altogether, these data show that unlike in healthy animals, ET and HIIT have divergent effects in the skeletal muscle of hypertensive rats. This suggests ET may be optimal at improving the oxidative capacity of skeletal muscle in animals with hypertension.

A call for adult congenital heart disease patient participation in cardiac rehabilitation.

Tanya M. Holloway ⁎, Caroline Chesssex , Sherry L. Grace , Erwin Oechslin , Lawrence L. Spriet , Adrienne H. Kovacs d,e a Cardiovascular Rehabilitation and Prevention Program, Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada b Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada c School of Kinesiology and Health Science, York University, Toronto, ON, Canada d University of Toronto, Toronto, ON, Canada e Toronto Congenital Cardiac Centre for Adults, Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada

Temporal response of angiogenesis and hypertrophy to resistance training in young men

Although endurance exercise training promotes angiogenesis and improves metabolic health, the effect of resistance training on this process is less well defined. We hypothesized that capillarization would increase proportionally, and concurrently, with muscle fiber hypertrophy in response to resistance training in young men. Methods In this double-blind, randomized control trial, 36 men (22 ± 1 yr) were randomized to placebo or protein supplementation, and participated in 12 wk of resistance training. Skeletal muscle biopsies were collected before and after 2, 4, 8, and 12 wk of training. Immunohistochemistry assessed fiber type–specific size and capillarization. Western blot and reverse transcription polymerase chain reaction assessed proteins involved in the molecular regulation of angiogenesis. Results Resistance training effectively increased Type I (15% ± 4%; P < 0.01) and Type II fiber cross-sectional area (28% ± 5%; P < 0.0001), an effect that tended to be further enhanced with protein supplementation in Type II fibers (P = 0.078). Capillary-to-fiber ratio significantly increased in Type I (P = 0.001) and II (P = 0.015) fibers after 12 wk of resistance exercise training and was evident after only 2 wk. Capillary-to-fiber perimeter exchange index increased in the Type I fibers only (P = 0.054) after 12 wk of training. Training resulted in a reduction in vascular endothelial growth factor mRNA. A (P = 0.008), while vascular endothelial growth factor receptor 2 (P = 0.016), hypoxia-inducible factor 1&agr; (P = 0.016), and endothelial nitric oxide synthase (P = 0.01) increased in both groups. Hypoxia-inducible factor 1&agr; protein content was higher in the protein group (main group effect, P = 0.02), and endothelial nitric oxide synthase content demonstrated a divergent relationship (time–group interaction, P = 0.049). Conclusions This study presents novel evidence that microvascular adaptations and the molecular pathways involved are elevated after 2 wk of a 12-wk resistance training program. Increases in muscle fiber cross-sectional area are effectively matched by the changes in the microvasculature, providing further support for resistance training programs to optimize metabolic health.

alpha-Linolenic acid and exercise training independently, and additively, decrease blood pressure and prevent diastolic dysfunction in obese Zucker rats

α‐linolenic acid (ALA) and exercise training both attenuate hyperlipidaemia‐related cardiovascular derangements, however, there is a paucity of information pertaining to their mechanisms of action when combined. We investigated both the independent and combined effects of exercise training and ALA consumption in obese Zucker rats, aiming to determine the potential for additive improvements in cardiovascular function. ALA and exercise training independently improved cardiac output, end‐diastolic volume, left ventricular fibrosis and mean blood pressure following a 4 week intervention. Combining ALA and endurance exercise yielded greater improvements in these parameters, independent of changes in markers of oxidative stress or endogenous anti‐oxidants. We postulate that divergent mechanisms of action may explain these changes: ALA increases peripheral vasodilation, and exercise training stimulates angiogenesis.

Rebuttal from Tanya M. Holloway and Lawrence L. Spriet

Wisløff et al. (2015) present epidemiological studies that demonstrate evidence for risk reduction as a result of high intensity interval training (HIIT). However, it is undeniable that many important health problems affecting modern society are due to the markedly different physical activity (PA) patterns from those to which humans were genetically adapted (Booth et al. 2008). When our current genome was originally selected, daily PA was obligatory and our biochemistry and physiology functioned optimally in such circumstances. Beginning with primitive civilizations, in which large amounts of energy expenditure were required to survive in the natural environment (25,000 years ago; 1240 kcal day−1), human energy expenditure has progressively declined (modern day 555 kcal day−1) (Eaton et al. 1988; Cordain et al. 1998) and lifestyle-related disease rates (e.g., diabetes mellitus, ischemic heart disease) have skyrocketed since the second industrial revolution. While there is evidence to support the use of HIIT, the evidence identifying detrimental effects of HIIT cannot be overlooked (Middleton et al. 2006; Scott et al. 2010), and may actually be more prevalent than previously reported (Levinger et al. 2015). Such negative evidence does not exist for moderate intensity PA. Natural selection shaped the human genome not to perform any particular form of activity exclusively, and we propose the graded addition of HIIT, where clinically appropriate, to daily moderate PA (e.g. 2–3 days of HIIT interspersed with days of moderate continuous training). This has been suggested to most closely mimic the activity patterns of our genetic ancestors (O’Keefe et al. 2011). Let us also not forget the important inclusion of other activities for overall health benefit, e.g. resistance training (Leenders et al. 2013). Ultimately, the significant literature on the benefits of moderate PA cannot be discounted, and HIIT should not be utilized in isolation, as the evidence for this remains limited compared to moderate daily PA. While we agree that a ‘lack of time’ remains the prominent reason for inadequate participation in PA, in our opinion it would be premature to suggest that 1 day per week of any form of exercise, HIIT or otherwise, is sufficient for optimal health. Ultimately, to reduce current PA recommendations in order to make it more attainable for those not meeting the guidelines is akin to suggesting partial smoking cessation, which would have enormous consequences on health compared to targeted total cessation (Morris et al. 2015). Also, to our knowledge, no evidence exists to suggest that a single bout of exercise is equivalent to the health benefits observed when meeting the current guidelines for daily PA. Let us not disregard what we have known for centuries: ‘Lack of activity destroys the good condition of every human being, while movement and methodical physical exercise save and preserve it’ (Plato 350 BC).