Redox Balance Differentially Affects Biomechanics in Permeabilized Single Muscle Fibres-Active and Passive Force Assessments with the Myorobot.

An oxidizing redox state imposes unique effects on the contractile properties of muscle. Permeabilized fibres show reduced active force generation in the presence of H2O2. However, our knowledge about the muscle fibre's elasticity or flexibility is limited due to shortcomings in assessing the passive stress-strain properties, mostly due to technically limited experimental setups. The MyoRobot is an automated biomechatronics platform that is well-capable of not only investigating calcium responsiveness of active contraction but also features precise stretch actuation to examine the passive stress-strain behaviour. Both were carried out in a consecutive recording sequence on the same fibre for 10 single fibres in total. We denote a significantly diminished maximum calcium-saturated force for fibres exposed to ≥500 µM H2O2, with no marked alteration of the pCa50 value. In contrast to active contraction (e.g., maximum isometric force activation), passive restoration stress (force per area) significantly increases for fibres exposed to an oxidizing environment, as they showed a non-linear stress-strain relationship. Our data support the idea that a highly oxidizing environment promotes non-linear fibre stiffening and confirms that our MyoRobot platform is a suitable tool for investigating redox-related changes in muscle biomechanics.

Redox Implications of Extreme Task Performance: The Case in Driver Athletes.

Redox homeostasis and redox-mediated signaling mechanisms are fundamental elements of human biology. Physiological levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) modulate a range of functional processes at the cellular, tissue, and systemic levels in healthy humans. Conversely, excess ROS or RNS activity can disrupt function, impairing the performance of daily activities. This article analyzes the impact of redox mechanisms on extreme task performance. Such activities (a) require complex motor skills, (b) are physically demanding, (c) are performed in an extreme environment, (d) require high-level executive function, and (e) pose an imminent risk of injury or death. The current analysis utilizes race car driving as a representative example. The physiological challenges of this extreme task include physical exertion, g loading, vibration, heat exposure, dehydration, noise, mental demands, and emotional factors. Each of these challenges stimulates ROS signaling, RNS signaling, or both, alters redox homeostasis, and exerts pro-oxidant effects at either the tissue or systemic levels. These redox mechanisms appear to promote physiological stress during race car driving and impair the performance of driver athletes.

Single muscle fibre biomechanics and biomechatronics - The challenges, the pitfalls and the future.

Interest in muscle biomechanics is growing with availabilities of patient biopsies and animal models related to muscle diseases, muscle wasting (sarcopenia, cachexia), exercise and drug effects. However, development of technologies or facilitated systems required to measure biomechanical and contractile properties of single fibres has not kept pace with this demand. Most studies use manual mechatronics systems that have not changed in decades and are confined to a few labs worldwide. Available commercial systems are expensive and limited in versatility, throughput and user-friendliness. We review major standard systems available from research labs and commercial sources, and benchmark those to our recently developed automated MyoRobot biomechatronics platform that provides versatility to cover multiple organ scales, is flexible in programming for active/passive muscle biomechanics using custom-made graphics user interfaces, employs on-the-fly data analyses and does not rely on external research microscopes. With higher throughput, this system blends Industry 4.0 automation principles into myology.

The Physiology of Auto Racing.

INTRODUCTION: Auto racing poses a unique set of physiologic challenges for athletes who compete in this sport. These challenges are not widely recognized due to the limited amount of original research in this field and the diffuse nature of this literature. The purpose of this article is to review the major physiologic challenges of auto racing and summarize what is currently known about athletes in this sport. CONCLUSIONS: The physical stressors of either driving or servicing the race car are overlaid with particular environmental challenges associated with racing (e.g., thermal, noise, carbon monoxide exposure) that increase the physiological stress on motorsport athletes. Physical stress reflects the muscular work required for car control and control of posture during high gravitational (g) loads: factors that predispose athletes to fatigue. The physiologic effects of these stressors include cardiovascular stress as reflected by prolonged elevation of heart rate, cardiac output, and oxygen consumption in both driver and pit athletes during competition. Psychological stress is evident in autonomic and endocrine responses of athletes during competition. The thermal stress of having to compete wearing multilayer fire suits and closed helmets in ambient temperatures of 50°C to 60°C results in the ubiquitous risk of dehydration. Published data show that both drivers and pit crew members are accomplished athletes with distinct challenges and abilities. There are gaps in the literature, especially in regard to female, older adult, and child participants. Additionally, minimal literature is available on appropriate training programs to offset the physiological challenges of auto racing.

Reactive Oxygen Species as Agents of Fatigue.

INTRODUCTION: For more than three decades, muscle biologists have been fascinated by reactive oxygen species (ROS) generated in exercising muscle and the potential role that ROS may play in fatigue. METHODS: Reports in the peer-reviewed literature were analyzed and published findings integrated to synthesize an overview of ROS as agents of fatigue. RESULTS: Muscle tissue contains multiple sources of ROS, and specific ROS molecules have been detected in muscle, including superoxide anions, hydrogen peroxide, and hydroxyl radicals. These species are present throughout the tissue, i.e., myofiber organelles and cytosol, extracellular space, and intravascular compartment, and ROS concentrations increase during strenuous contractions. Direct ROS exposure evokes many of the same changes that occur in muscle during fatigue, suggesting a possible relationship. The hypothesis that ROS play a causal role in fatigue has been tested extensively, a large body of data have been compiled, and the once-controversial verdict is now in: ROS accumulation in working muscle clearly contributes to the loss of function that occurs in fatigue. This is evident in a range of experimental settings ranging from muscle fiber bundles in vitro to neuromuscular preparations in situ, from volitional exercise of small muscle groups to whole-body exercise by elite athletes. CONCLUSION: The robust capacity of antioxidant pretreatment to delay fatigue provides compelling evidence that ROS play a causal role in this process. There are caveats to this story of course, issues related to the type of antioxidant and mode of administration. Also, the translation of this laboratory concept into clinical practice has been slow. Still, antioxidant therapy has the potential to benefit individuals who experience premature fatigue and this remains a promising area for future research.

Disease-Induced Skeletal Muscle Atrophy and Fatigue.

Numerous health problems, including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders, often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal muscle weakness can increase the duration of hospitalization, result in exercise limitation, and contribute to a poor quality of life. Importantly, skeletal muscle atrophy is also associated with increased morbidity and mortality of patients. Therefore, improving our understanding of the mechanism(s) responsible for skeletal muscle weakness and fatigue in patients is a required first step to develop clinical protocols to prevent these skeletal muscle problems. This review will highlight the consequences and potential mechanisms responsible for skeletal muscle atrophy and fatigue in patients experiencing acute critical illness, cancer, chronic inflammatory diseases, and neurological disorders.

Redox interventions to increase exercise performance.

Skeletal muscle continually produces reactive oxygen species (ROS) and nitric oxide (NO) derivatives. Both oxidant cascades have complex effects on muscle contraction, metabolic function and tissue perfusion. Strenuous exercise increases oxidant production by muscle, limiting performance during endurance exercise tasks. Conversely, redox interventions that modulate ROS or NO activity have the potential to improve performance. Antioxidants have long been known to buffer ROS activity and lessen oxidative perturbations during exercise. The capacity to enhance human performance varies among antioxidant categories. Vitamins, provitamins and nutriceuticals often blunt oxidative changes at the biochemical level but do not enhance performance. In contrast, reduced thiol donors have been shown to delay fatigue or increase endurance under a variety of experimental conditions. Dietary nitrate supplementation has recently emerged as a second redox strategy for increasing endurance. Purified nitrate salts and nitrate-rich foods, notably beetroot and beetroot juice, are reported to lessen the oxygen cost of exercise, increase efficiency, and enhance performance during endurance tasks. These findings are exciting but enigmatic since nitrate per se has little bioactivity and cannot be converted to NO by mammalian cells. Overall, the available data suggest exercise endurance can be augmented by redox-active supplements, either reduced thiol donors or dietary nitrates. These findings have clear implications for athletes seeking a competitive edge. More importantly, interventions that increase endurance may benefit individuals whose physical activity is limited by illness, ageing, or frailty.

Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits.

The beneficial effects of physical activity (PA) are well documented, yet the mechanisms by which PA prevents disease and improves health outcomes are poorly understood. To identify major gaps in knowledge and potential strategies for catalyzing progress in the field, the NIH convened a workshop in late October 2014 entitled "Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits." Presentations and discussions emphasized the challenges imposed by the integrative and intermittent nature of PA, the tremendous discovery potential of applying "-omics" technologies to understand interorgan crosstalk and biological networking systems during PA, and the need to establish an infrastructure of clinical trial sites with sufficient expertise to incorporate mechanistic outcome measures into adequately sized human PA trials. Identification of the mechanisms that underlie the link between PA and improved health holds extraordinary promise for discovery of novel therapeutic targets and development of personalized exercise medicine.